Non-Small Cell Lung CancerPhase 2HUDSONNCT03334617
Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy
A Phase 2 study testing Durvalumab, Danvatirsen and Ceralasertib in people with Non-Small Cell Lung Cancer, run by AstraZeneca at 45 sites in 8 countries.
Trial summary
This is an open-label, multi-centre, umbrella Phase II study in participants with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Durvalumab, Danvatirsen and Ceralasertib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 528 participants
- Where
- 45 sitesin 8 countries
- Study dates
- 18 Dec 2017to 11 Sep 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years of age at the time of signing the informed consent form.
- Participant must have histologically or cytologically confirmed metastatic or locally advanced and recurrent non-small-cell lung cancer (NSCLC) which is progressing.
- Participants eligible for second- or later-line therapy, who must have received an anti-programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) containing therapy and a platinum-doublet regimen for locally advanced or metastatic NSCLC either separately or in combination. Prior durvalumab is acceptable. The participant must have had disease progression on a prior line of anti-PD-1/PD-L1 therapy.
- Eastern Cooperative Oncology Group/World Health Organization (ECOG/WHO) performance status of 0 to 1, and a minimum life expectancy of 12 weeks.
- Participant must have at least 1 lesion that can be accurately measured. A previously irradiated lesion can be considered a target lesion if the lesion has clearly progressed.
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal participants.
Who cannot join
- Participants whose tumour samples have targetable alterations in epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) at initial diagnosis are excluded. In addition, participants whose tumour samples are known to have targetable alterations in ROS1, BRAF, MET or RET, are to be excluded.
- Active or prior documented autoimmune or inflammatory disorders.
- Active infection including tuberculosis, hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive human immunodeficiency virus [HIV] 1/2 antibodies).
- Female participant who are pregnant or breastfeeding, or male or female participants of reproductive potential who are not willing to employ effective birth control.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients, or history of severe hypersensitivity reactions to other monoclonal antibodies.
- Participant has spinal cord compression or symptomatic brain metastases.
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Participants may receive treatment with bisphosphonates or receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors for the treatment of bone metastases.
- History of active primary immunodeficiency.
Trial locations and contacts
45 sites in 8 countries.
45 sites in 8 countries
United States17 sites
Research Site
Baltimore, Maryland, 21224
Research Site
Baltimore, Maryland, 21287
Research Site
Boston, Massachusetts, 02215
Research Site
Chicago, Illinois, 60637
Research Site
Duarte, California, 91010
Research Site
Fairfax, Virginia, 22031
Research Site
Fullerton, California, 92835
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093
Research Site
Los Angeles, California, 90095
Research Site
Nashville, Tennessee, 37203
Research Site
Nashville, Tennessee, 37212
Research Site
New York, New York, 10032
Research Site
Philadelphia, Pennsylvania, 19111
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
St Louis, Missouri, 63110
Research Site
Washington D.C., District of Columbia, 20016
Canada5 sites
Research Site
Brampton, Ontario, L6R 3J7
Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Montreal, Quebec, H2X 3E4
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Toronto, Ontario, M5G 2M9
Austria4 sites
Research Site
Innsbruck, 6020
Research Site
Salzburg, 5020
Research Site
Vienna, 1140
Research Site
Vienna, 1210
France4 sites
Research Site
Bordeaux, 33076
Research Site
Nantes, 44093
Research Site
Paris, 75877
Research Site
Villejuif, 94800
Germany4 sites
Research Site
Berlin, 12203
Research Site
Esslingen a.N., 73730
Research Site
Großhansdorf, 22927
Research Site
Heidelberg, 69126
Israel4 sites
Research Site
Haifa, 31096
Research Site
Kfar Saba, 95847
Research Site
Petah Tikva, 49100
Research Site
Ramat Gan, 5265601
Spain4 sites
Research Site
Barcelona, 08036
Research Site
Madrid, 28007
Research Site
Madrid, 28034
Research Site
Seville, 41009
South Korea3 sites
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 6351
About this study
Official title: An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients With Non-Small Cell Lung Cancer, Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (HUDSON).
This is an open-label, multi-centre, umbrella Phase II study in participants with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms.
Read the detailed description
This is an open-label, multi-centre, umbrella Phase II study in participants with metastatic non-small cell lung cancer (NSCLC) who have progressed on an anti-programmed cell death-1/anti-programmed cell death ligand 1 (anti-PD-1/PD-L1) containing therapy. This study is modular in design, consisting of a number of treatment cohorts, allowing evaluation of the efficacy, safety, and tolerability of multiple treatment arms. There is currently no established therapy for participants who have received immune checkpoint inhibitors and platinum-doublet therapies, and novel treatments are urgently needed.
This protocol has a modular design, with the potential for future treatment arms to be added via protocol amendment.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Durvalumab, Danvatirsen, Ceralasertib, Vistusertib, Olaparib
- Keywords
- Non-small cell lung cancer, NSCLC, anti-PD-1/PD-L1, umbrella study, Durvalumab, MEDI4736, Olaparib, AZD2281, AZD9150, AZD6738, Vistusertib, AZD2014, Oleclumab, MEDI9447, Trastuzumab deruxtecan, DS-8201a, cediranib, AZD2171
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Participants will receive IV infusion of durvalumab as stated in arm description.
DanvatirsenDrug
Also called AZD9150
Participants will receive IV infusion of danvatirsen as stated in arm description.
CeralasertibDrug
Also called AZD6738
Participants will receive oral tablet of ceralasertib as stated in arm description.
VistusertibDrug
Participants will receive oral tablets of vistusertib as stated in arm description.
OlaparibDrug
Participants will receive oral tablets of olaparib as stated in arm description.
OleclumabDrug
Participants will receive IV infusion of oleclumab as stated in arm description.
Trastuzumab deruxtecanDrug
Also called T-DXd
Participants will receive IV infusion of trastuzumab deruxtecan as stated in arm description.
CediranibDrug
Also called AZD2171
Participants will receive oral tablets of cediranib as stated in arm description.
| Study group | Role | What they receive |
|---|---|---|
| Module 1 Cohort A.1.HRR: Durvalumab 1500 mg + Olaparib 300 mg | Experimental | Participants with detectable aberrations, mutation detected in a homologous recombination repair gene (HRRm) will receive IV infusion of durvalumab 1500 mg every 4 weeks (Q4W) in combination with oral olaparib 300 mg (2 × 150 mg) tablets twice a day (BD) until disease progression is confirmed. Receives: Drug: Durvalumab; Drug: Olaparib |
| Module 1 Cohort A.1.LKB: Durvalumab 1500 mg + Olaparib 300 mg | Experimental | Participants with detectable aberrations in liver kinase B1 (LKB1) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed. Receives: Drug: Durvalumab; Drug: Olaparib |
| Module 1 Cohort B.1.PRI: Durvalumab 1500 mg + Olaparib 300 mg | Experimental | Participants who had anti-programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (primary resistance; PRI) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed. Receives: Drug: Durvalumab; Drug: Olaparib |
| Module 1 Cohort B.1.ACQ: Durvalumab 1500 mg + Olaparib 300 mg | Experimental | Participants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (acquired resistance; ACQ) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed. Receives: Drug: Durvalumab; Drug: Olaparib |
| Module 2 Cohort B.2.PRI: Durvalumab 1500 mg + Danvatirsen 200 mg | Experimental | Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of AZD9150 (danvatirsen) 200 mg as loading dose on Days 1, 3, 5 of Cycle 0 (7-day-lead-in period). Thereafter, participants will receive AZD9150 200 mg every week (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Danvatirsen |
| Module 2 Cohort B.2.ACQ: Durvalumab 1500 mg + Danvatirsen 200 mg | Experimental | Participants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of AZD9150 (danvatirsen) 200 mg as loading dose on Days 1, 3, 5 of Cycle 0 (7-day-lead-in period). Thereafter, participants will receive AZD9150 200 mg every week (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Danvatirsen |
| Module 3 Cohort A.3.ATM: Durvalumab 1500 mg + AZD6738 240 mg | Experimental | Participants who are ataxia telangiectasia mutated (ATM)-deficiecy will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD in each cycle between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Ceralasertib |
| Module 3 Cohort B.3.PRI: Durvalumab 1500 mg + AZD6738 240 mg | Experimental | Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Ceralasertib |
| Module 3 Cohort B.3.ACQ: Durvalumab 1500 mg + AZD6738 240 mg | Experimental | Participants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Ceralasertib |
| Module 4 Cohort A.4.RIC: Durvalumab 1500 mg + Vistusertib 125 mg | Experimental | Participants with detectable genetic amplifications in rapamycin-insensitive companion of mechanistic target of rapamycin complex-2 (RICTOR) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral vistusertib 125 mg tablets BD on an intermittent dosing schedule of 2 days on, 5 days off, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Vistusertib |
| Module 5 Cohort A.5.73H: Durvalumab 1500 mg + Oleclumab 3000 mg | Experimental | Participants with high expression of cluster of differentiation 73 (CD73) will receive IV infusion of oleclumab 3000 mg every 2 weeks (Q2W) for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Oleclumab |
| Module 5 Cohort B.5.PRI: Durvalumab 1500 mg + Oleclumab 3000 mg | Experimental | Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of oleclumab 3000 mg Q2W for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Oleclumab |
| Module 5 Cohort B.5.ACQ: Durvalumab 1500 mg + Oleclumab 3000 mg | Experimental | Participants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of oleclumab 3000 mg Q2W for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Oleclumab |
| Module 6 Cohort A.6.HER2e: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg | Experimental | Participants whose tumours express human epidermal growth factor receptor 2 (HER2) mutations will receive IV infusion of trastuzumab deruxtecan (T-DXd) 5.4 mg/kg every 3 weeks (Q3W) in combination with IV infusion of durvalumab 1120 mg Q3W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Trastuzumab deruxtecan |
| Module 6 Cohort A.6.HER2m: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg | Experimental | Participants whose tumours harbour selected HER2 mutations will receive IV infusion of T-DXd 5.4 mg/kg Q3W in combination with IV infusion of durvalumab 1120 mg Q3W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Trastuzumab deruxtecan |
| Module 7 Cohort B.7.ACQ: Durvalumab 1500 mg + Cediranib 20 mg | Experimental | Participants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral cediranib (AZD2171) 20 mg tablets daily for 5 days on, 2 days off (starting on Cycle 1 Day 1 of durvalumab), until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Cediranib |
| Module 8 Cohort A.8.ATM: Ceralasertib 240 mg | Experimental | Participants who are ATM-deficient or with detectable aberrations in the ATM gene will receive oral ceralasertib (AZD6738) 240 mg tablets BD from Day 1 to Day 14 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Ceralasertib |
| Module 9 Cohort B.9.PRI: Durvalumab 1500 mg + Ceralasertib 240 mg | Experimental | Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib (AZD6738) 240 mg tablets BD for 14 days from Day 15 to Day 28 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Ceralasertib |
| Module 9 Cohort B.9.ACQ: Durvalumab 1500 mg + Ceralasertib 240 mg | Experimental | Participants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of durvalumab 1500 mg Q4W plus oral ceralasertib (AZD6738) 240 mg tablets BD for 14 days from Day 15 to Day 28 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Ceralasertib |
| Module 10 Cohort C.10.160: Durvalumab 1500 mg + Ceralasertib 160 mg | Experimental | Participants, independent of their molecular aberration status, will receive oral ceralasertib (AZD6738) 160 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib 160 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Ceralasertib |
| Module 10 Cohort C.10.240: Durvalumab 1500 mg + Ceralasertib 240 mg | Experimental | Participants, independent of their molecular aberration status, will receive oral ceralasertib (AZD6738) 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. Receives: Drug: Durvalumab; Drug: Ceralasertib |
| Module 11 Cohort C.11.240: AZD6738 240 mg | Experimental | Participants, independent of their molecular aberration status, will receive oral AZD6738 tablet 240 mg for 7 days (Days 1 to 7) in each 28-day cycle until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. Receives: Drug: Ceralasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1)
Objective response was defined as participants with a confirmed investigator-assessed response complete response (CR) or partial response (PR) based on RECIST v 1.1. The CR is defined as disappearance of all target (TL) and non-target lesions (NTL), and any pathological lymph node (whether target or nontarget) must have reduction in short axis to <10 mm. The PR is defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum diameters, as long as criteria for progressive disease (PD) are not met. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from date of first documentation. Percentage of participants with objective response was reported.
Measured: Baseline (<=28 days before treatment), then every 6 weeks for 24 weeks from Cycle 1 Day 1, then every 8 weeks (every 9 weeks in Module 6) until disease progression or 90 days after study drug discontinuation (approximately 2 years)
Secondary outcomes (10)
Overall Survival (OS)
The OS is defined as the time from the first dose of any study drug until death due to any cause regardless of whether the participant withdraws from study treatment or receives subsequent cancer therapy. The overall survival was analyzed using the Kaplan-Meier method.
Measured: Every 3 months after safety follow-up visit (90 days after study drug discontinuation) until planned database lock for a module (either 12 months after last participant has started treatment or when 75% of participants died) (approximately up to 2 years)
Progression-Free Survival (PFS) Per RECIST v1.1
The PFS is defined as time from first dose of any study drug until date of objective disease progression (PD) per RECIST v1.1 or death by any cause, regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy prior to progression. The PD is defined as a >= 20% increase in the sum of diameters of TLs and an absolute increase of >= 5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or unequivocal progression of existing NTL. The PFS was analyzed using the Kaplan-Meier method
Measured: Every 3 months after safety follow-up visit (90 days after study drug discontinuation) until planned database lock for a module (either 12 months after last participant has started treatment or when 75% of participants died) (approximately up to 2 years)
Best Percentage Change From Baseline in Tumour Size
The best percentage change in tumour size from baseline i.e. the maximum reduction from baseline or the minimum increase from baseline in absence of a reduction from baseline based on all post baseline assessments is reported. Tumour size is sum of the longest diameters (or short axis measurements for lymph nodes) of the target lesions. Baseline was defined as last evaluable assessment prior to starting treatment. The percentage change in target lesion tumour size at each week X for which data are available was obtained for each participant taking the difference between the sum of the target lesions at each week X and the sum of the target lesions at baseline divided by the sum of the target lesions at baseline multiplied by 100 (i.e. [week X - baseline]/baseline * 100).
Measured: Baseline (<=28 days prior to starting treatment) then every 6 weeks for first 24 weeks relative to the date of first dose/combination therapy (Cycle 1 Day 1), then every 8 weeks (except Module 6)/9 weeks (Module 6) thereafter (approximately up to 2 years)
Percentage of Participants With Disease Control (DC) Per RECIST v1.1
Module (M) 1, 4, 5, 6, 7, 8, 9, 11: DCR at 12 and 24 weeks is defined as percentage of participants who have best overall response (BoR) of CR or PR in first 13/25 weeks, respectively, post start of any study drug or with duration of SD for at least 11/23 weeks, respectively, after start of any study drug. M2, M3, M10: DCR at 12 and 24 weeks is defined as percentage of participants who have BoR of CR or PR within first 100 days (M2, M3, M10) or 184 days (M2, M3, M10) after start of any study drug, or have SD lasting at least 86 days (M2)/82 days (M3, M10), respectively, or 170 days (M2)/166 days (M3, M10), respectively, post start of any study drug. CR is defined as disappearance of all TL and NTLs, and any pathological lymph node (whether target or nontarget) must have reduction in short axis to <10 mm. PR is defined as at least 30% decrease in sum of diameters of TLs, taking as reference baseline sum diameters, as long as criteria for PD are not met.
Measured: At 12 and 24 weeks after the start of study drug
Duration of Response (DoR) Per RECIST v1.1
The DoR is defined as the time from the first documented confirmed response (CR or PR) until the first documented PD or death in the absence of disease progression. The CR is defined as disappearance of all TLs and NTLs, and any pathological lymph node (whether target or nontarget) must have reduction in short axis to <10 mm. The PR is defined as at least a 30 decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters, as long as criteria for PD are not met. The PD is defined as a >=20% increase in the sum of diameters of TLs and an absolute increase of >=5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters, or unequivocal progression of existing NTL. The DoR was analyzed using the Kaplan-Meier method.
Measured: Baseline (<=28 days before treatment), then every 6 weeks for 24 weeks from Cycle 1 Day 1, then every 8 weeks (every 9 weeks in Module 6) until disease progression or 90 days after study drug discontinuation (approximately 2 years)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Measured: Day 1 thorugh 58.6 months (maximum observed duration)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, and urinalysis.
Measured: Day 1 thorugh 58.6 months (maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, pulse rate, temperature, and respiration rate).
Measured: Day 1 thorugh 58.6 months (maximum observed duration)
Number of Participants With Abnormal Physical Examination Findings Reported as TEAEs
Number of participants with abnormal physical examination findings reported as TEAEs are reported. Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the pre-dose assessment was reported as an AE.
Measured: Day 1 thorugh 58.6 months (maximum observed duration)
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs
Number of participants with abnormal ECGs reported as TEAEs are reported.
Measured: Day 1 thorugh 58.6 months (maximum observed duration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start18 Dec 2017
- Primary completion13 Sep 2024
- Study completion11 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is an open-label, multi-centre, umbrella Phase II study in participants with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms. Within each module, there will be treatment cohorts.
- Masking
- None (open label)
- Enrolment
- 528 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Heymach, M.D, Ph.D, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03334617
- Sponsor's protocol ID
- D6185C00001
- Other IDs
- 138050, 2023-509004-15-00, 2017-002208-28, 2017, 2023
- Acronym
- HUDSON
- Status last verified
- Oct 2025
- First submitted
- 22 Sep 2017
- Last updated
- 27 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Besse B, Pons-Tostivint E, Park K, Hartl S, Forde PM, Hochmair MJ, Awad MM, Thomas M, Goss G, Wheatley-Price P, Shepherd FA, Florescu M, Cheema P, Chu QSC, Kim SW, Morgensztern D, Johnson ML, Cousin S, Kim DW, Moskovitz MT, Vicente D, Aronson B, Hobson R, Ambrose HJ, Khosla S, Reddy A, Russell DL, Keddar MR, Conway JP, Barrett JC, Dean E, Kumar R, Dressman M, Jewsbury PJ, Iyer S, Barry ST, Cosaert J, Heymach JV. Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. Nat Med. 2024 Mar;30(3):716-729. doi: 10.1038/s41591-024-02808-y. Epub 2024 Feb 13.
PubMed 38351187
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multi-Drug, Biomarker-Directed, Multi-Centre Phase II Umbrella Study in Patients With Non-Small Cell Lung Cancer, Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy (HUDSON).
- ClinicalTrials.gov ID
- NCT03334617
- Acronym / sponsor ID
- HUDSON / D6185C00001
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- Non-small cell lung cancer, NSCLC, anti-PD-1/PD-L1, umbrella study, Durvalumab, MEDI4736, Olaparib, AZD2281
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 528 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 18 Dec 2017 (actual)
- Primary completion
- 13 Sep 2024 (actual)
- Study completion
- 11 Sep 2026 (estimated)
- First posted
- 7 Nov 2017 (actual)
- Results
- Posted 27 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multi-centre, umbrella Phase II study in participants with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms.
Detailed description
This is an open-label, multi-centre, umbrella Phase II study in participants with metastatic non-small cell lung cancer (NSCLC) who have progressed on an anti-programmed cell death-1/anti-programmed cell death ligand 1 (anti-PD-1/PD-L1) containing therapy. This study is modular in design, consisting of a number of treatment cohorts, allowing evaluation of the efficacy, safety, and tolerability of multiple treatment arms. There is currently no established therapy for participants who have received immune checkpoint inhibitors and platinum-doublet therapies, and novel treatments are urgently needed.
This protocol has a modular design, with the potential for future treatment arms to be added via protocol amendment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 22
- Model description
- This is an open-label, multi-centre, umbrella Phase II study in participants with metastatic NSCLC who have progressed on an anti-PD-1/PD-L1 containing therapy. This study is modular in design, allowing initial assessment of the efficacy, safety, and tolerability of multiple treatment arms. Within each module, there will be treatment cohorts.
| Arm | Type | Receives |
|---|---|---|
| Module 1 Cohort A.1.HRR: Durvalumab 1500 mg + Olaparib 300 mg | Experimental | Drug: Durvalumab, Drug: OlaparibParticipants with detectable aberrations, mutation detected in a homologous recombination repair gene (HRRm) will receive IV infusion of durvalumab 1500 mg every 4 weeks (Q4W) in combination with oral olaparib 300 mg (2 × 150 mg) tablets twice a day (BD) until disease progression is confirmed. |
| Module 1 Cohort A.1.LKB: Durvalumab 1500 mg + Olaparib 300 mg | Experimental | Drug: Durvalumab, Drug: OlaparibParticipants with detectable aberrations in liver kinase B1 (LKB1) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed. |
| Module 1 Cohort B.1.PRI: Durvalumab 1500 mg + Olaparib 300 mg | Experimental | Drug: Durvalumab, Drug: OlaparibParticipants who had anti-programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (primary resistance; PRI) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed. |
| Module 1 Cohort B.1.ACQ: Durvalumab 1500 mg + Olaparib 300 mg | Experimental | Drug: Durvalumab, Drug: OlaparibParticipants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (acquired resistance; ACQ) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed. |
| Module 2 Cohort B.2.PRI: Durvalumab 1500 mg + Danvatirsen 200 mg | Experimental | Drug: Durvalumab, Drug: DanvatirsenParticipants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of AZD9150 (danvatirsen) 200 mg as loading dose on Days 1, 3, 5 of Cycle 0 (7-day-lead-in period). Thereafter, participants will receive AZD9150 200 mg every week (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 2 Cohort B.2.ACQ: Durvalumab 1500 mg + Danvatirsen 200 mg | Experimental | Drug: Durvalumab, Drug: DanvatirsenParticipants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of AZD9150 (danvatirsen) 200 mg as loading dose on Days 1, 3, 5 of Cycle 0 (7-day-lead-in period). Thereafter, participants will receive AZD9150 200 mg every week (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 3 Cohort A.3.ATM: Durvalumab 1500 mg + AZD6738 240 mg | Experimental | Drug: Durvalumab, Drug: CeralasertibParticipants who are ataxia telangiectasia mutated (ATM)-deficiecy will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD in each cycle between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. |
| Module 3 Cohort B.3.PRI: Durvalumab 1500 mg + AZD6738 240 mg | Experimental | Drug: Durvalumab, Drug: CeralasertibParticipants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. |
| Module 3 Cohort B.3.ACQ: Durvalumab 1500 mg + AZD6738 240 mg | Experimental | Drug: Durvalumab, Drug: CeralasertibParticipants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. |
| Module 4 Cohort A.4.RIC: Durvalumab 1500 mg + Vistusertib 125 mg | Experimental | Drug: Durvalumab, Drug: VistusertibParticipants with detectable genetic amplifications in rapamycin-insensitive companion of mechanistic target of rapamycin complex-2 (RICTOR) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral vistusertib 125 mg tablets BD on an intermittent dosing schedule of 2 days on, 5 days off, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. |
| Module 5 Cohort A.5.73H: Durvalumab 1500 mg + Oleclumab 3000 mg | Experimental | Drug: Durvalumab, Drug: OleclumabParticipants with high expression of cluster of differentiation 73 (CD73) will receive IV infusion of oleclumab 3000 mg every 2 weeks (Q2W) for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 5 Cohort B.5.PRI: Durvalumab 1500 mg + Oleclumab 3000 mg | Experimental | Drug: Durvalumab, Drug: OleclumabParticipants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of oleclumab 3000 mg Q2W for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 5 Cohort B.5.ACQ: Durvalumab 1500 mg + Oleclumab 3000 mg | Experimental | Drug: Durvalumab, Drug: OleclumabParticipants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of oleclumab 3000 mg Q2W for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 6 Cohort A.6.HER2e: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg | Experimental | Drug: Durvalumab, Drug: Trastuzumab deruxtecanParticipants whose tumours express human epidermal growth factor receptor 2 (HER2) mutations will receive IV infusion of trastuzumab deruxtecan (T-DXd) 5.4 mg/kg every 3 weeks (Q3W) in combination with IV infusion of durvalumab 1120 mg Q3W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 6 Cohort A.6.HER2m: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg | Experimental | Drug: Durvalumab, Drug: Trastuzumab deruxtecanParticipants whose tumours harbour selected HER2 mutations will receive IV infusion of T-DXd 5.4 mg/kg Q3W in combination with IV infusion of durvalumab 1120 mg Q3W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 7 Cohort B.7.ACQ: Durvalumab 1500 mg + Cediranib 20 mg | Experimental | Drug: Durvalumab, Drug: CediranibParticipants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral cediranib (AZD2171) 20 mg tablets daily for 5 days on, 2 days off (starting on Cycle 1 Day 1 of durvalumab), until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 8 Cohort A.8.ATM: Ceralasertib 240 mg | Experimental | Drug: CeralasertibParticipants who are ATM-deficient or with detectable aberrations in the ATM gene will receive oral ceralasertib (AZD6738) 240 mg tablets BD from Day 1 to Day 14 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 9 Cohort B.9.PRI: Durvalumab 1500 mg + Ceralasertib 240 mg | Experimental | Drug: Durvalumab, Drug: CeralasertibParticipants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib (AZD6738) 240 mg tablets BD for 14 days from Day 15 to Day 28 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 9 Cohort B.9.ACQ: Durvalumab 1500 mg + Ceralasertib 240 mg | Experimental | Drug: Durvalumab, Drug: CeralasertibParticipants who had progressive disease > 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of durvalumab 1500 mg Q4W plus oral ceralasertib (AZD6738) 240 mg tablets BD for 14 days from Day 15 to Day 28 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria. |
| Module 10 Cohort C.10.160: Durvalumab 1500 mg + Ceralasertib 160 mg | Experimental | Drug: Durvalumab, Drug: CeralasertibParticipants, independent of their molecular aberration status, will receive oral ceralasertib (AZD6738) 160 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib 160 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. |
| Module 10 Cohort C.10.240: Durvalumab 1500 mg + Ceralasertib 240 mg | Experimental | Drug: Durvalumab, Drug: CeralasertibParticipants, independent of their molecular aberration status, will receive oral ceralasertib (AZD6738) 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. |
| Module 11 Cohort C.11.240: AZD6738 240 mg | Experimental | Drug: CeralasertibParticipants, independent of their molecular aberration status, will receive oral AZD6738 tablet 240 mg for 7 days (Days 1 to 7) in each 28-day cycle until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- At least 18 years of age at the time of signing the informed consent form.
- Participant must have histologically or cytologically confirmed metastatic or locally advanced and recurrent non-small-cell lung cancer (NSCLC) which is progressing.
- Participants eligible for second- or later-line therapy, who must have received an anti-programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) containing therapy and a platinum-doublet regimen for locally advanced or metastatic NSCLC either separately or in combination. Prior durvalumab is acceptable. The participant must have had disease progression on a prior line of anti-PD-1/PD-L1 therapy.
- Eastern Cooperative Oncology Group/World Health Organization (ECOG/WHO) performance status of 0 to 1, and a minimum life expectancy of 12 weeks.
- Participant must have at least 1 lesion that can be accurately measured. A previously irradiated lesion can be considered a target lesion if the lesion has clearly progressed.
Key exclusion criteria (8 listed)
- Participants whose tumour samples have targetable alterations in epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) at initial diagnosis are excluded. In addition, participants whose tumour samples are known to have targetable alterations in ROS1, BRAF, MET or RET, are to be excluded.
- Active or prior documented autoimmune or inflammatory disorders.
- Active infection including tuberculosis, hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive human immunodeficiency virus [HIV] 1/2 antibodies).
- Female participant who are pregnant or breastfeeding, or male or female participants of reproductive potential who are not willing to employ effective birth control.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients, or history of severe hypersensitivity reactions to other monoclonal antibodies.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabParticipants will receive IV infusion of durvalumab as stated in arm description. | Drug | Module 1 Cohort A.1.HRR: Durvalumab 1500 mg + Olaparib 300 mg, Module 1 Cohort A.1.LKB: Durvalumab 1500 mg + Olaparib 300 mg, Module 1 Cohort B.1.ACQ: Durvalumab 1500 mg + Olaparib 300 mg, Module 1 Cohort B.1.PRI: Durvalumab 1500 mg + Olaparib 300 mg, Module 10 Cohort C.10.160: Durvalumab 1500 mg + Ceralasertib 160 mg, Module 10 Cohort C.10.240: Durvalumab 1500 mg + Ceralasertib 240 mg, Module 2 Cohort B.2.ACQ: Durvalumab 1500 mg + Danvatirsen 200 mg, Module 2 Cohort B.2.PRI: Durvalumab 1500 mg + Danvatirsen 200 mg, Module 3 Cohort A.3.ATM: Durvalumab 1500 mg + AZD6738 240 mg, Module 3 Cohort B.3.ACQ: Durvalumab 1500 mg + AZD6738 240 mg, Module 3 Cohort B.3.PRI: Durvalumab 1500 mg + AZD6738 240 mg, Module 4 Cohort A.4.RIC: Durvalumab 1500 mg + Vistusertib 125 mg, Module 5 Cohort A.5.73H: Durvalumab 1500 mg + Oleclumab 3000 mg, Module 5 Cohort B.5.ACQ: Durvalumab 1500 mg + Oleclumab 3000 mg, Module 5 Cohort B.5.PRI: Durvalumab 1500 mg + Oleclumab 3000 mg, Module 6 Cohort A.6.HER2e: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg, Module 6 Cohort A.6.HER2m: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg, Module 7 Cohort B.7.ACQ: Durvalumab 1500 mg + Cediranib 20 mg, Module 9 Cohort B.9.ACQ: Durvalumab 1500 mg + Ceralasertib 240 mg, Module 9 Cohort B.9.PRI: Durvalumab 1500 mg + Ceralasertib 240 mg |
| DanvatirsenAlso: AZD9150Participants will receive IV infusion of danvatirsen as stated in arm description. | Drug | Module 2 Cohort B.2.ACQ: Durvalumab 1500 mg + Danvatirsen 200 mg, Module 2 Cohort B.2.PRI: Durvalumab 1500 mg + Danvatirsen 200 mg |
| CeralasertibAlso: AZD6738Participants will receive oral tablet of ceralasertib as stated in arm description. | Drug | Module 10 Cohort C.10.160: Durvalumab 1500 mg + Ceralasertib 160 mg, Module 10 Cohort C.10.240: Durvalumab 1500 mg + Ceralasertib 240 mg, Module 11 Cohort C.11.240: AZD6738 240 mg, Module 3 Cohort A.3.ATM: Durvalumab 1500 mg + AZD6738 240 mg, Module 3 Cohort B.3.ACQ: Durvalumab 1500 mg + AZD6738 240 mg, Module 3 Cohort B.3.PRI: Durvalumab 1500 mg + AZD6738 240 mg, Module 8 Cohort A.8.ATM: Ceralasertib 240 mg, Module 9 Cohort B.9.ACQ: Durvalumab 1500 mg + Ceralasertib 240 mg, Module 9 Cohort B.9.PRI: Durvalumab 1500 mg + Ceralasertib 240 mg |
| VistusertibParticipants will receive oral tablets of vistusertib as stated in arm description. | Drug | Module 4 Cohort A.4.RIC: Durvalumab 1500 mg + Vistusertib 125 mg |
| OlaparibParticipants will receive oral tablets of olaparib as stated in arm description. | Drug | Module 1 Cohort A.1.HRR: Durvalumab 1500 mg + Olaparib 300 mg, Module 1 Cohort A.1.LKB: Durvalumab 1500 mg + Olaparib 300 mg, Module 1 Cohort B.1.ACQ: Durvalumab 1500 mg + Olaparib 300 mg, Module 1 Cohort B.1.PRI: Durvalumab 1500 mg + Olaparib 300 mg |
| OleclumabParticipants will receive IV infusion of oleclumab as stated in arm description. | Drug | Module 5 Cohort A.5.73H: Durvalumab 1500 mg + Oleclumab 3000 mg, Module 5 Cohort B.5.ACQ: Durvalumab 1500 mg + Oleclumab 3000 mg, Module 5 Cohort B.5.PRI: Durvalumab 1500 mg + Oleclumab 3000 mg |
| Trastuzumab deruxtecanAlso: T-DXdParticipants will receive IV infusion of trastuzumab deruxtecan as stated in arm description. | Drug | Module 6 Cohort A.6.HER2e: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg, Module 6 Cohort A.6.HER2m: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg |
| CediranibAlso: AZD2171Participants will receive oral tablets of cediranib as stated in arm description. | Drug | Module 7 Cohort B.7.ACQ: Durvalumab 1500 mg + Cediranib 20 mg |
Primary outcome
Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1)
Time frame: Baseline (<=28 days before treatment), then every 6 weeks for 24 weeks from Cycle 1 Day 1, then every 8 weeks (every 9 weeks in Module 6) until disease progression or 90 days after study drug discontinuation (approximately 2 years)
Objective response was defined as participants with a confirmed investigator-assessed response complete response (CR) or partial response (PR) based on RECIST v 1.1. The CR is defined as disappearance of all target (TL) and non-target lesions (NTL), and any pathological lymph node (whether target or nontarget) must have reduction in short axis to <10 mm. The PR is defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum diameters, as long as criteria for progressive disease (PD) are not met. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from date of first documentation. Percentage of participants with objective response was reported.
10 secondary outcomes
Overall Survival (OS)
Time frame: Every 3 months after safety follow-up visit (90 days after study drug discontinuation) until planned database lock for a module (either 12 months after last participant has started treatment or when 75% of participants died) (approximately up to 2 years)
Progression-Free Survival (PFS) Per RECIST v1.1
Time frame: Every 3 months after safety follow-up visit (90 days after study drug discontinuation) until planned database lock for a module (either 12 months after last participant has started treatment or when 75% of participants died) (approximately up to 2 years)
Best Percentage Change From Baseline in Tumour Size
Time frame: Baseline (<=28 days prior to starting treatment) then every 6 weeks for first 24 weeks relative to the date of first dose/combination therapy (Cycle 1 Day 1), then every 8 weeks (except Module 6)/9 weeks (Module 6) thereafter (approximately up to 2 years)
Percentage of Participants With Disease Control (DC) Per RECIST v1.1
Time frame: At 12 and 24 weeks after the start of study drug
Duration of Response (DoR) Per RECIST v1.1
Time frame: Baseline (<=28 days before treatment), then every 6 weeks for 24 weeks from Cycle 1 Day 1, then every 8 weeks (every 9 weeks in Module 6) until disease progression or 90 days after study drug discontinuation (approximately 2 years)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: Day 1 thorugh 58.6 months (maximum observed duration)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Time frame: Day 1 thorugh 58.6 months (maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Time frame: Day 1 thorugh 58.6 months (maximum observed duration)
Number of Participants With Abnormal Physical Examination Findings Reported as TEAEs
Time frame: Day 1 thorugh 58.6 months (maximum observed duration)
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs
Time frame: Day 1 thorugh 58.6 months (maximum observed duration)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38351187Besse B, Pons-Tostivint E, Park K, Hartl S, Forde PM, Hochmair MJ, Awad MM, Thomas M, Goss G, Wheatley-Price P, Shepherd FA, Florescu M, Cheema P, Chu QSC, Kim SW, Morgensztern D, Johnson ML, Cousin S, Kim DW, Moskovitz MT, Vicente D, Aronson B, Hobson R, Ambrose HJ, Khosla S, Reddy A, Russell DL, Keddar MR, Conway JP, Barrett JC, Dean E, Kumar R, Dressman M, Jewsbury PJ, Iyer S, Barry ST, Cosaert J, Heymach JV. Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. Nat Med. 2024 Mar;30(3):716-729. doi: 10.1038/s41591-024-02808-y. Epub 2024 Feb 13.
- Redacted SAPLink provided by the sponsor.
- Redacted CSPLink provided by the sponsor.
- Redacted CSR synopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Heymach, M.D, Ph.D principal investigator
M.D. Anderson Cancer Center
45 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab, Danvatirsen and Ceralasertib in people with Non-Small Cell Lung Cancer, run by AstraZeneca at 45 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Canada, Austria, France, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) (time frame: Baseline (<=28 days before treatment), then every 6 weeks for 24 weeks from Cycle 1 Day 1, then every 8 weeks (every 9 weeks in Module 6) until disease progression or 90 days after study drug discontinuation (approximately 2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03334617, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2025.