Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and NeckPhase 1/2NCT02499328
Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck
A Phase 1/2 study testing AZD9150, MEDI4736 and AZD5069 in people with Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and Neck, run by AstraZeneca at 44 sites in 6 countries.
Trial summary
This multicentre, open-label, Phase 1b/2 study is designed as a 2 part study consisting of a dose-escalation, safety run-in Part A and a dose-expansion Part B Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- AZD9150, MEDI4736 and AZD5069
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 340 participants
- Where
- 44 sitesin 6 countries
- Study dates
- 6 Aug 2015to 8 Oct 2025
- Phase
- Phase 1/2
- 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 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients must be at least 18 years of age.
- Has an Eastern Cooperative Oncology Group (ECOG) PS score of 0 or 1.
- Has measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm by computerised tomography (CT) scan, except lymph nodes which must have minimum short axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases). Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation unless there is documented progression after therapy.
- Has undergone ≤3 previous regimens (depending on treatment arm) of cytoreductive therapies including, but not limited to, platinum-based compounds, taxanes, or 5-fluorouracil. for B7 \& B8, no prior systemic treatments should have been received for RM SCCHN
- Adequate organ and marrow function
- Female subjects of childbearing potential and male subjects with partners of childbearing potential should ensure use of a highly effective method of birth control as defined in study protocol
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- Additional inclusion for part A: Has a histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.
- Addition inclusion for Part A (A6) Has a histological confirmation of castrate-resistant prostate cancer
- Additional inclusion for Part B:Has histologically and/or cytologically confirmed SCCHN that is RM and not amendable to curative therapy by surgery or radiation. Squamous cell carcinoma of the head and neck originating from the following sites is eligible: oral cavity, oropharynx, larynx, or hypopharynx. Has at least 1 SCCHN tumour lesion (TL) amenable to biopsy and must have failed, refused, or has been found to be ineligible for least 1 prior platinum-based chemotherapy for RM-SCCHN Additional inclusion criteria for Arms B1 \& B2: must have had prior exposure to anti PDL-1 antibody
- Arms B1-B6: Has undergone 1-3 previous regimens of cytoreductive chemo-therapies Arm B7 \& B8: with no prior exposure to anti-PD-(L)1 therapies and have received no prior systemic treatment for RM SCCHN
Who cannot join
- Spinal cord compression unless asymptomatic and not requiring steroids for at least 4 weeks before the start of study treatment. - Presently has a second malignancy other than SCCHN, or history of treatment for invasive cancer other than SCCHN in the past 3 years. Exceptions are: Previously treated in-situ carcinoma (ie, noninvasive) Cervical carcinoma stage 1B or less Noninvasive basal cell and squamous cell skin carcinoma Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate-specific antigen, and not requiring ongoing antiandrogen hormonal therapy
- Patients must have completed any previous cancer-related treatments before enrolment. Any concurrent chemotherapy [Chemotherapy washout within 21 days or 5 half-lives (whichever is shorter) from enrolment], radiotherapy, immunotherapy, or biologic, or hormonal therapy for cancer excludes the patient (concurrent use of hormones for noncancer-related conditions [eg, insulin for diabetes and hormone replacement therapy] is acceptable),
- Experiencing CTCAE grade >1 events, experienced immune-related grade ≥3AEs with prior immunotherapy
- Has active or prior autoimmune disease within the past 2 years
- Has active or prior inflammatory bowel disease or primary immunodeficiency
- Undergone an organ transplant that requires use of immunosuppressive treatment
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- Abnormalities in rhythm, conduction or morphology of resting 12-lead ECG
- uncontrolled comorbid conditions
- Received a live attenuated vaccine within 30 days of first study dose, unable to take oral medications
- History of allergic reactions to study compounds or excepients Additional exclusion criteria Part A: Patients with clinically active brain metastases and prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.
- Additional exclusion criteria Part B: Patients with brain metastases (known or suspected) Additional exclusion criteria Part B: treatment arms B3, B4, B5, B6, B7 and B8: prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.
Trial locations and contacts
44 sites in 6 countries.
44 sites in 6 countries
United States19 sites
Research Site
Billings, Montana, 59101
Research Site
Birmingham, Alabama, 35294
Research Site
Boston, Massachusetts, 02111
Research Site
Cincinnati, Ohio, 45267-2827
Research Site
Denver, Colorado, 80218
Research Site
Detroit, Michigan, 48201
Research Site
Duarte, California, 91010
Research Site
Fairfax, Virginia, 22031
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093
Research Site
Lafayette, Indiana, 47905
Research Site
Los Angeles, California, 90024
Research Site
Los Angeles, California, 90089
Research Site
Morristown, New Jersey, 07960
Research Site
Orange, California, 92868-3298
Research Site
Plantation, Florida, 33324
Research Site
San Francisco, California, 94158
Research Site
Sarasota, Florida, 34232
Research Site
Seattle, Washington, 98109
Germany8 sites
Research Site
Berlin, 12200
Research Site
Cologne, 50670
Research Site
Dresden, 1307
Research Site
Frankfurt, 60488
Research Site
Hamburg, 20246
Research Site
Hanover, 30625
Research Site
Jena, 07743
Research Site
München, 81675
United Kingdom6 sites
Research Site
Birmingham, B15 2TH
Research Site
London, SE1 9RT
Research Site
London, SW3 6JB
Research Site
Manchester, M20 4BX
Research Site
Surrey, SM2 5PT
Research Site
Taunton, TA1 5DA
Belgium5 sites
Research Site
Antwerp, 2020
Research Site
Brussels, 1000
Research Site
Brussels, 1200
Research Site
Edegem, 2650
Research Site
Namur, 5000
Spain5 sites
Research Site
Barcelona, 08035
Research Site
Hospitalet deLlobregat, 08907
Research Site
Madrid, 28040
Research Site
Madrid, 28041
Research Site
Toledo, 45004
About this study
Official title: A Phase 1b/2, Open-Label, Multicentre Study Assessing the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of MEDI4736 in Combination With AZD9150 or AZD5069 in Patients With Advanced Solid Malignancies and Subsequently Comparing AZD9150 and AZD5069 Both as Monotherapy and in Combination With MEDI4736 as Second Line Treatment in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck.
This multicentre, open-label, Phase 1b/2 study is designed as a 2 part study consisting of a dose-escalation, safety run-in Part A and a dose-expansion Part B
Read the detailed description
The dose-escalation Part A of this study will involve patients with advanced solid malignancies refractory to standard therapy or for which no standard of care regimen currently exists. Approximately 30 evaluable patients per treatment arm (A1 or A2) will be enrolled. A3 will test viability of alternate dosing schedule for AZD5069, A4/A5 will evaluate AZD9150/AZD5069 in fixed dose combination with MEDI4736 and tremelimumab in solid tumors. there may also be safety run in cohorts enrolled (A6/A7) in specific solid tumor types (breast and prostate cancer).
Once the maximum tolerated doses (MTDs) for each of the 2 agents (AZD9150/AZD5069)in combination with MEDI4736 have been identified or the maximum doses of each of the 2 agents in combination with MEDI4736 have been reached, the dose expansion Part B of the study would commence. It will be conducted in patients with recurrent and/or metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN). Between 68 and 266 eligible patients will be enrolled and will randomly assigned to 1 of the following 6 treatment arms or non randomized arm B7:
- Treatment arm B1: AZD9150 in combination with MEDI4736 in patients with prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B2: AZD5069 in combination with MEDI4736 in patients with prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B3: AZD9150 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (2L RM SCCHN)
- Treatment arm B4: AZD5069 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B5: AZD9150 alone in patients with no prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B6: AZD5069 alone in patients with no prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B7: (non randomized): AZD9150 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (1L RM SCCHN)
- Treatment arm B8: (non randomized): AZD9150 (every two weeks) in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (1L RM SCCHN)
- Being tested
- AZD9150, MEDI4736, AZD5069, tremelimumab (treme)
- Keywords
- Carcinoma of the Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9150Drug
AZD9150
MEDI4736Drug
MEDI4736
AZD5069Drug
AZD5069
tremelimumab (treme)Drug
tremelimumab
| Study group | Role | What they receive |
|---|---|---|
| Part A1: AZD9150 / MEDI4736 | Experimental | Patients allocated in cohort of arm A1 (AZD9150/MEDI4736 will be evaluated for DLT until an MTD is achieved. Receives: Drug: AZD9150; Drug: MEDI4736 |
| Part A2: AZD5069 / MEDI4736 | Experimental | Patients allocated in cohort of arm A2 (AZD5069/MEDI4736 will be evaluated for DLT until an MTD is achieved. Receives: Drug: MEDI4736; Drug: AZD5069 |
| Part B1:AZD9150+MEDI4736:PDL1 pretreated | Experimental | Patients in arm B1 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. Receives: Drug: AZD9150; Drug: MEDI4736 |
| Part B2:AZD5069+MEDI4736:PDL1 pretreated | Experimental | Patients in arm B2 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. Receives: Drug: MEDI4736; Drug: AZD5069 |
| Part B3: AZD9150+MED4736:naiive 2L | Experimental | Patients in arm B3 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. Receives: Drug: AZD9150; Drug: MEDI4736 |
| Part B4:AZD5069+MEDI4736:naiive patients | Experimental | Patients in arm B4 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. Receives: Drug: MEDI4736; Drug: AZD5069 |
| Part B5: AZD9150 in naiive patients | Experimental | Patients in arm B5 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival Receives: Drug: AZD9150 |
| Part B6:AZD5069 in naiive patients | Experimental | Patients in arm B6 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival Receives: Drug: AZD5069 |
| Part A3: AZD5069/MEDI4736 | Experimental | Patients allocated in cohort of arm A3 (AZD5069/MEDI4736) will be evaluated for DLT and viability as alternate dosing option for Phase 2 studies Receives: Drug: MEDI4736; Drug: AZD5069 |
| Part A4: AZD9150/Treme/MEDI4736 | Experimental | Patients allocated in cohort of arm A4 (AZD9150/treme/MEDI4736) will be evaluated for DLT and MTD Receives: Drug: AZD9150; Drug: MEDI4736; Drug: tremelimumab (treme) |
| Part A5: AZD5069/Treme/MEDI4736 | Experimental | Patients allocated in cohort of arm A5 (AZD5069/treme/MEDI4736) will be evaluated for DLT and MTD. Receives: Drug: MEDI4736; Drug: AZD5069; Drug: tremelimumab (treme) |
| Part A6: AZD9150/MEDI4736 | Experimental | Patients allocated in cohort of arm A6 (AZD9150/MEDI4736) will be evaluated for safety, PK and PD. Receives: Drug: AZD9150; Drug: MEDI4736 |
| Part A7: AZD5069/MEDI4736 | Experimental | Patients allocated in cohort of arm A7 (AZD5069/MEDI4736) will be evaluated for safety, PK and PD. Receives: Drug: MEDI4736; Drug: AZD5069 |
| Part B7: AZD9150+MEDI4736: naiive 1L | Experimental | Patients in Arm B7 will be evaluated for efficacy until disease progression and then followed up for safety and survival Receives: Drug: AZD9150; Drug: MEDI4736 |
| Part B8: AZD9150 (every other week)+MEDI4736: naive 1L | Experimental | Patients in Arm B8 will be evaluated for efficacy until disease progression and then followed up for safety and survival Receives: Drug: AZD9150; Drug: MEDI4736 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Danvatirsen With Durvalumab MTDs (Maximum Tolerated Dose) or Recommended Doses for Dose-expansion
After completion of DLT period (35 days) for the maximum dose cohort. A CRM-based approach was used to identify the set of dose combinations where the incidence of DLT was ≤ 33%. The dose with expected DLT incidence closest and below 0.33 at this point was the "model estimated" MTD. During trial execution, the Safety Review Committee (SRC) determined the MTD.
Measured: 35 days
Part A: AZD5069 With Durvalumab MTDs (Maximum Tolerated Dose) or Recommended Doses for Dose-expansion
After completion of DLT period (35 days) for the maximum dose cohort. A CRM-based approach was used to identify the set of dose combinations where the incidence of DLT was ≤ 33%. The dose with expected DLT incidence closest and below 0.33 at this point was the "model estimated" MTD. During trial execution, the Safety Review Committee (SRC) determined the MTD.
Measured: 35 days
Part A: Safety and Tolerability in Terms of Adverse Events
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Measured: At every treatment and follow up visit until disease progression, an average of 1 year.
Part B: ORR (Objective Response Rate) in Patients With IL/2L RM-SCCHN.
proportion of patients who have an objective response at a given visit. ORR will be summarised by treatment group. Objective rate is defined as a CR or PR according to RECIST 1.1.
Measured: Assessed at every even-numbered cycles with RECIST until disease progression, up to 12 months.
Secondary outcomes (23)
Part A and B: AZD9150 AUC0-6h at Lead in Day-7
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to calculate AUC, we need to have enough PK samples collected to enable AUC estimation. That is why we have a difference in actual AUC calculated number of subjects vs number of subjects participated.
Measured: Lead in day -7, AUC from time 0 to 6h (post dose).
Part A and B: AZD9150 Cmax at Lead in Day -7
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Cmax we need to have samples at end of infusion, which was not available for all the subjects in PK analysis set. That is why there is a difference between Cmax calculated number of subjects vs number of subjects participated.
Measured: Lead in day -7
Part A and B: AZD9150 AUC0-6h at Cycle 2 Day 1
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to calculate AUC, we need to have enough PK samples collected to enable AUC estimation. That is why we have a difference in actual AUC calculated number of subjects vs number of subjects participated.
Measured: Cycle 2 day 1, AUC from time 0 to 6 h post dose
Part A and B: AZD9150 Cmax at Cycle 2 Day 1
Measured: Cycle 2 day 1
Part A and B: AZD5069 AUC0-12h at Lead in Day -7
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to calculate AUC, we need to have enough PK samples collected to enable AUC estimation. That is why we have a difference in actual AUC calculated number of subjects vs number of subjects participated.
Measured: Lead in day -7, AUC from time 0 to 12h post dose
Part A and B: AZD5069 Cmax at Lead in Day -7
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Cmax we need to have samples at Tmax, which was not available for all the subjects in PK analysis set. That is why there is a difference between Cmax calculated number of subjects vs number of subjects participated.
Measured: Lead in day -7
Part A and B: AZD5069 Cssmax at Cycle 2 Day 1
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Cmax we need to have samples at around Tmax, which was not available for all the subjects in PK analysis set. That is why there is a difference between Cmax calculated number of subjects vs number of subjects participated.
Measured: Cycle 2 day 1
Part A and B: AZD5069 AUCss at Cycle 2 Day 1
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to calculate AUC, we need to have enough PK samples collected to enable AUC estimation. That is why we have a difference in actual AUC calculated number of subjects vs number of subjects participated.
Measured: Cycle 2 day 1
Part A and B: Durvalumab Cmax After Single Dose at Cycle 1 Day 1
Measured: Cycle 1 day 1
Part A and B: Durvalumab Ctrough After Multiple Doses at Cycle 4 Day 1
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Ctrough we need to have samples at predose, which was not available for all the subjects in PK analysis set. That is why there is a difference between Ctrough calculated number of subjects vs number of subjects participated.
Measured: Cycle 4 day 1
Part A and B: Durvalumab Cmax After Multiple Doses at Cycle 8 Day 1
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Cmax we need to have samples at end of infusion, which was not available for all the subjects in PK analysis set. That is why there is a difference between Cmax calculated number of subjects vs number of subjects participated.
Measured: Cycle 8 day 1
Part A and B: Treme Cmax After Single Dose
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Cmax we need to have samples at end of infusion, which was not available for all the subjects in PK analysis set. That is why there is a difference between Cmax calculated number of subjects vs number of subjects participated.
Measured: Cycle 1 day 1
Part A and B: Treme Ctrough After Multiple Doses at Cycle 4 Day 1
If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Ctrough we need to have samples at predose, which was not available for all the subjects in PK analysis set. That is why there is a difference between Ctrough calculated number of subjects vs number of subjects participated.
Measured: Cycle 4 day 1
Part A and B: Immunogenecity as Percent of ADA Positive Subjects
Subject was considered ADA positive if any post dose samples had ADA positive result. Result was not stratified based on post dose time points.
Measured: Throughout the study, up to 3.3 years
Part A: Antitumour Activity in Monotherapy and Combination Arms of Study
complete response, partial response, stable disease or progressive disease based on RECIST
Measured: assessed at every even numbered cycle with RECIST until disease progression, an average of 1 year
Part B: Safety and Tolerability in Terms of Adverse Events
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Measured: At every treatment and follow up visit until disease progression, an average of 1 year.
Part B: Secondary Measures Change in Efficacy - Disease Control Rate
Disease control rate is confirmed complete response (CR), confirmed partial response (PR) and stable disease (SD)
Measured: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 12 months
Part B: Secondary Measures Change in Efficacy - Duration of Overall Response
Duration of overall response is according to RECIST 1.1 criteria measured from the time measurement criteria are first met for CR or PR, whichever is first recorded, until the first date that recurrent or PD is objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR is only applied to treatment groups where at least one response patient was recorded.
Measured: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 48 months
Part B: Secondary Measures Change in Efficacy - PFS
progression-free survival (PFS): defined as the time from randomisation to the first documentation of PD as determined by the Investigator or death from any cause, whichever occurs first. Only includes progression events that occur within 126 days of the last evaluable assessment
Measured: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 12 months
Part B: Secondary Measures Change in Efficacy - OS
overall survival (OS) - defined as the time from treatment allocation to death from any cause
Measured: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 15 months
Part B: Secondary Measures Change in Efficacy - OS at 12 Months
proportion of patients alive at 12 months: the percentage of patients surviving at 12 months after randomization to study drug
Measured: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 12 months
Part B: Evaluation of AZD9150 Pharmacodynamics: Change in STAT3 RNA Level From Baseline
Percent STAT3 RNA change in expression level in peripheral blood in patients who had baseline (Screening or Day -7) sample for comparison. Data were only available for B1, B3, B5, B7 and B8.
Measured: At Cycle 2 Day 1 vs. Baseline
Part B: Evaluation of PDL1 Expression
Tumors with PDL1-positive tumor cells at the designated cutoff. Data were only available for B1, B2, B3, B4, B7 and B8.
Measured: in baseline tumor samples
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study start6 Aug 2015
- Primary completion28 Feb 2020
- Study completion8 Oct 2025
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.
- Other trials for Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and NeckStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 340 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- MedImmune LLC
- Responsible party
- Sponsor
- Investigators
- Dr David Hong, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499328
- Sponsor's protocol ID
- D5660C00004
- Other IDs
- 2015-002525-19, 2015
- Status last verified
- Jan 2026
- First submitted
- 18 Jun 2015
- Last updated
- 11 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2, Open-Label, Multicentre Study Assessing the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of MEDI4736 in Combination With AZD9150 or AZD5069 in Patients With Advanced Solid Malignancies and Subsequently Comparing AZD9150 and AZD5069 Both as Monotherapy and in Combination With MEDI4736 as Second Line Treatment in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck.
- ClinicalTrials.gov ID
- NCT02499328
- Acronym / sponsor ID
- D5660C00004
- Keywords
- Carcinoma of the Head and Neck
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 340 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- MedImmune LLC
- Study start
- 6 Aug 2015 (actual)
- Primary completion
- 28 Feb 2020 (actual)
- Study completion
- 8 Oct 2025 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Posted 23 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multicentre, open-label, Phase 1b/2 study is designed as a 2 part study consisting of a dose-escalation, safety run-in Part A and a dose-expansion Part B
Detailed description
The dose-escalation Part A of this study will involve patients with advanced solid malignancies refractory to standard therapy or for which no standard of care regimen currently exists. Approximately 30 evaluable patients per treatment arm (A1 or A2) will be enrolled. A3 will test viability of alternate dosing schedule for AZD5069, A4/A5 will evaluate AZD9150/AZD5069 in fixed dose combination with MEDI4736 and tremelimumab in solid tumors. there may also be safety run in cohorts enrolled (A6/A7) in specific solid tumor types (breast and prostate cancer).
Once the maximum tolerated doses (MTDs) for each of the 2 agents (AZD9150/AZD5069)in combination with MEDI4736 have been identified or the maximum doses of each of the 2 agents in combination with MEDI4736 have been reached, the dose expansion Part B of the study would commence. It will be conducted in patients with recurrent and/or metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN). Between 68 and 266 eligible patients will be enrolled and will randomly assigned to 1 of the following 6 treatment arms or non randomized arm B7:
- Treatment arm B1: AZD9150 in combination with MEDI4736 in patients with prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B2: AZD5069 in combination with MEDI4736 in patients with prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B3: AZD9150 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (2L RM SCCHN)
- Treatment arm B4: AZD5069 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B5: AZD9150 alone in patients with no prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B6: AZD5069 alone in patients with no prior exposure to anti-PD-(L)1 antibodies
- Treatment arm B7: (non randomized): AZD9150 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (1L RM SCCHN)
- Treatment arm B8: (non randomized): AZD9150 (every two weeks) in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (1L RM SCCHN)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Part A1: AZD9150 / MEDI4736 | Experimental | Drug: AZD9150, Drug: MEDI4736Patients allocated in cohort of arm A1 (AZD9150/MEDI4736 will be evaluated for DLT until an MTD is achieved. |
| Part A2: AZD5069 / MEDI4736 | Experimental | Drug: MEDI4736, Drug: AZD5069Patients allocated in cohort of arm A2 (AZD5069/MEDI4736 will be evaluated for DLT until an MTD is achieved. |
| Part B1:AZD9150+MEDI4736:PDL1 pretreated | Experimental | Drug: AZD9150, Drug: MEDI4736Patients in arm B1 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. |
| Part B2:AZD5069+MEDI4736:PDL1 pretreated | Experimental | Drug: MEDI4736, Drug: AZD5069Patients in arm B2 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. |
| Part B3: AZD9150+MED4736:naiive 2L | Experimental | Drug: AZD9150, Drug: MEDI4736Patients in arm B3 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. |
| Part B4:AZD5069+MEDI4736:naiive patients | Experimental | Drug: MEDI4736, Drug: AZD5069Patients in arm B4 will be evaluated for efficacy until disease progression and then followed-up for safety and survival. |
| Part B5: AZD9150 in naiive patients | Experimental | Drug: AZD9150Patients in arm B5 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival |
| Part B6:AZD5069 in naiive patients | Experimental | Drug: AZD5069Patients in arm B6 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival |
| Part A3: AZD5069/MEDI4736 | Experimental | Drug: MEDI4736, Drug: AZD5069Patients allocated in cohort of arm A3 (AZD5069/MEDI4736) will be evaluated for DLT and viability as alternate dosing option for Phase 2 studies |
| Part A4: AZD9150/Treme/MEDI4736 | Experimental | Drug: AZD9150, Drug: MEDI4736, Drug: tremelimumab (treme)Patients allocated in cohort of arm A4 (AZD9150/treme/MEDI4736) will be evaluated for DLT and MTD |
| Part A5: AZD5069/Treme/MEDI4736 | Experimental | Drug: MEDI4736, Drug: AZD5069, Drug: tremelimumab (treme)Patients allocated in cohort of arm A5 (AZD5069/treme/MEDI4736) will be evaluated for DLT and MTD. |
| Part A6: AZD9150/MEDI4736 | Experimental | Drug: AZD9150, Drug: MEDI4736Patients allocated in cohort of arm A6 (AZD9150/MEDI4736) will be evaluated for safety, PK and PD. |
| Part A7: AZD5069/MEDI4736 | Experimental | Drug: MEDI4736, Drug: AZD5069Patients allocated in cohort of arm A7 (AZD5069/MEDI4736) will be evaluated for safety, PK and PD. |
| Part B7: AZD9150+MEDI4736: naiive 1L | Experimental | Drug: AZD9150, Drug: MEDI4736Patients in Arm B7 will be evaluated for efficacy until disease progression and then followed up for safety and survival |
| Part B8: AZD9150 (every other week)+MEDI4736: naive 1L | Experimental | Drug: AZD9150, Drug: MEDI4736Patients in Arm B8 will be evaluated for efficacy until disease progression and then followed up for safety and survival |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male and female patients must be at least 18 years of age.
- Has an Eastern Cooperative Oncology Group (ECOG) PS score of 0 or 1.
- Has measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm by computerised tomography (CT) scan, except lymph nodes which must have minimum short axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases). Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation unless there is documented progression after therapy.
- Has undergone ≤3 previous regimens (depending on treatment arm) of cytoreductive therapies including, but not limited to, platinum-based compounds, taxanes, or 5-fluorouracil. for B7 \& B8, no prior systemic treatments should have been received for RM SCCHN
- Adequate organ and marrow function
Key exclusion criteria (11 listed)
- Spinal cord compression unless asymptomatic and not requiring steroids for at least 4 weeks before the start of study treatment. - Presently has a second malignancy other than SCCHN, or history of treatment for invasive cancer other than SCCHN in the past 3 years. Exceptions are: Previously treated in-situ carcinoma (ie, noninvasive) Cervical carcinoma stage 1B or less Noninvasive basal cell and squamous cell skin carcinoma Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate-specific antigen, and not requiring ongoing antiandrogen hormonal therapy
- Patients must have completed any previous cancer-related treatments before enrolment. Any concurrent chemotherapy [Chemotherapy washout within 21 days or 5 half-lives (whichever is shorter) from enrolment], radiotherapy, immunotherapy, or biologic, or hormonal therapy for cancer excludes the patient (concurrent use of hormones for noncancer-related conditions [eg, insulin for diabetes and hormone replacement therapy] is acceptable),
- Experiencing CTCAE grade >1 events, experienced immune-related grade ≥3AEs with prior immunotherapy
- Has active or prior autoimmune disease within the past 2 years
- Has active or prior inflammatory bowel disease or primary immunodeficiency
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 |
|---|---|---|
| AZD9150AZD9150 | Drug | Part A1: AZD9150 / MEDI4736, Part A4: AZD9150/Treme/MEDI4736, Part A6: AZD9150/MEDI4736, Part B1:AZD9150+MEDI4736:PDL1 pretreated, Part B3: AZD9150+MED4736:naiive 2L, Part B5: AZD9150 in naiive patients, Part B7: AZD9150+MEDI4736: naiive 1L, Part B8: AZD9150 (every other week)+MEDI4736: naive 1L |
| MEDI4736MEDI4736 | Drug | Part A1: AZD9150 / MEDI4736, Part A2: AZD5069 / MEDI4736, Part A3: AZD5069/MEDI4736, Part A4: AZD9150/Treme/MEDI4736, Part A5: AZD5069/Treme/MEDI4736, Part A6: AZD9150/MEDI4736, Part A7: AZD5069/MEDI4736, Part B1:AZD9150+MEDI4736:PDL1 pretreated, Part B2:AZD5069+MEDI4736:PDL1 pretreated, Part B3: AZD9150+MED4736:naiive 2L, Part B4:AZD5069+MEDI4736:naiive patients, Part B7: AZD9150+MEDI4736: naiive 1L, Part B8: AZD9150 (every other week)+MEDI4736: naive 1L |
| AZD5069AZD5069 | Drug | Part A2: AZD5069 / MEDI4736, Part A3: AZD5069/MEDI4736, Part A5: AZD5069/Treme/MEDI4736, Part A7: AZD5069/MEDI4736, Part B2:AZD5069+MEDI4736:PDL1 pretreated, Part B4:AZD5069+MEDI4736:naiive patients, Part B6:AZD5069 in naiive patients |
| tremelimumab (treme)tremelimumab | Drug | Part A4: AZD9150/Treme/MEDI4736, Part A5: AZD5069/Treme/MEDI4736 |
Primary outcome
Part A: Danvatirsen With Durvalumab MTDs (Maximum Tolerated Dose) or Recommended Doses for Dose-expansion
Time frame: 35 days
After completion of DLT period (35 days) for the maximum dose cohort. A CRM-based approach was used to identify the set of dose combinations where the incidence of DLT was ≤ 33%. The dose with expected DLT incidence closest and below 0.33 at this point was the "model estimated" MTD. During trial execution, the Safety Review Committee (SRC) determined the MTD.
Part A: AZD5069 With Durvalumab MTDs (Maximum Tolerated Dose) or Recommended Doses for Dose-expansion
Time frame: 35 days
After completion of DLT period (35 days) for the maximum dose cohort. A CRM-based approach was used to identify the set of dose combinations where the incidence of DLT was ≤ 33%. The dose with expected DLT incidence closest and below 0.33 at this point was the "model estimated" MTD. During trial execution, the Safety Review Committee (SRC) determined the MTD.
Part A: Safety and Tolerability in Terms of Adverse Events
Time frame: At every treatment and follow up visit until disease progression, an average of 1 year.
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Part B: ORR (Objective Response Rate) in Patients With IL/2L RM-SCCHN.
Time frame: Assessed at every even-numbered cycles with RECIST until disease progression, up to 12 months.
proportion of patients who have an objective response at a given visit. ORR will be summarised by treatment group. Objective rate is defined as a CR or PR according to RECIST 1.1.
23 secondary outcomes
Part A and B: AZD9150 AUC0-6h at Lead in Day-7
Time frame: Lead in day -7, AUC from time 0 to 6h (post dose).
Part A and B: AZD9150 Cmax at Lead in Day -7
Time frame: Lead in day -7
Part A and B: AZD9150 AUC0-6h at Cycle 2 Day 1
Time frame: Cycle 2 day 1, AUC from time 0 to 6 h post dose
Part A and B: AZD9150 Cmax at Cycle 2 Day 1
Time frame: Cycle 2 day 1
Part A and B: AZD5069 AUC0-12h at Lead in Day -7
Time frame: Lead in day -7, AUC from time 0 to 12h post dose
Part A and B: AZD5069 Cmax at Lead in Day -7
Time frame: Lead in day -7
Part A and B: AZD5069 Cssmax at Cycle 2 Day 1
Time frame: Cycle 2 day 1
Part A and B: AZD5069 AUCss at Cycle 2 Day 1
Time frame: Cycle 2 day 1
Part A and B: Durvalumab Cmax After Single Dose at Cycle 1 Day 1
Time frame: Cycle 1 day 1
Part A and B: Durvalumab Ctrough After Multiple Doses at Cycle 4 Day 1
Time frame: Cycle 4 day 1
Part A and B: Durvalumab Cmax After Multiple Doses at Cycle 8 Day 1
Time frame: Cycle 8 day 1
Part A and B: Treme Cmax After Single Dose
Time frame: Cycle 1 day 1
Part A and B: Treme Ctrough After Multiple Doses at Cycle 4 Day 1
Time frame: Cycle 4 day 1
Part A and B: Immunogenecity as Percent of ADA Positive Subjects
Time frame: Throughout the study, up to 3.3 years
Part A: Antitumour Activity in Monotherapy and Combination Arms of Study
Time frame: assessed at every even numbered cycle with RECIST until disease progression, an average of 1 year
Part B: Safety and Tolerability in Terms of Adverse Events
Time frame: At every treatment and follow up visit until disease progression, an average of 1 year.
Part B: Secondary Measures Change in Efficacy - Disease Control Rate
Time frame: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 12 months
Part B: Secondary Measures Change in Efficacy - Duration of Overall Response
Time frame: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 48 months
Part B: Secondary Measures Change in Efficacy - PFS
Time frame: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 12 months
Part B: Secondary Measures Change in Efficacy - OS
Time frame: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 15 months
Part B: Secondary Measures Change in Efficacy - OS at 12 Months
Time frame: Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 12 months
Part B: Evaluation of AZD9150 Pharmacodynamics: Change in STAT3 RNA Level From Baseline
Time frame: At Cycle 2 Day 1 vs. Baseline
Part B: Evaluation of PDL1 Expression
Time frame: in baseline tumor samples
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Related InfoLink 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.
Dr David Hong, MD principal investigator
M.D. Anderson Cancer Center
44 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD9150, MEDI4736 and AZD5069 in people with Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and Neck, run by AstraZeneca at 44 sites in 6 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 10 inclusion and 11 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: finished, as of the sponsor's last update on 11 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Germany, United Kingdom, Belgium, Spain and 1 more country. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 23 Nov 2021). 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?
Part A: Danvatirsen With Durvalumab MTDs (Maximum Tolerated Dose) or Recommended Doses for Dose-expansion (time frame: 35 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Feb 2026.