Non-small Cell Lung CancerPhase 2NeoCOAST-2NCT05061550
Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer
A Phase 2 study testing Durvalumab, Oleclumab and Monalizumab in people with Non-small Cell Lung Cancer, run by AstraZeneca at 97 sites in 12 countries.
Trial summary
The study is intended to assess the safety and efficacy of perioperative treatment with Durvalumab in combination with Oleclumab, Monalizumab, or AZD0171 and platinum doublet chemotherapy (CTX); or Volrustomig or Rilvegostomig in combination with CTX; or Datopotamab deruxtecan (Dato-DXd) in combination with Durvalumab… Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Durvalumab, Oleclumab and Monalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 630 participants
- Where
- 97 sitesin 12 countries
- Study dates
- 14 Apr 2022to 28 May 2030
- Phase
- Phase 2
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 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed NSCLC patients with resectable disease (Stage IIA to Stage IIIB).
- WHO or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate organ and bone marrow function.
- Provision of tumour samples (newly acquired or archival tumour tissue [≤ 6 months old]) to confirm Programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) status.
- Adequate pulmonary function.
Who cannot join
- Participants with sensitising EGFR mutations or ALK translocations.
- Participants with baseline PD-L1 expression status <1% (Arms 6 and 7 only).
- Active or prior documented autoimmune or inflammatory disorders.
- Uncontrolled intercurrent illness, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active bleeding diseases, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement.
- History of another primary malignancy.
- Participants with small-cell lung cancer or mixed small-cell lung cancer.
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- History of active primary immunodeficiency.
- History of non-infectious interstitial lung disease (ILD) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- Participants who have preoperative radiotherapy treatment as part of their care plan.
- Participants who require or may require pneumonectomy, segmentectomies, or wedge resections, as assessed by their surgeon at baseline, to obtain potentially curative resection of primary tumour.
- QTcF (QT interval corrected by Fridericia's formula) interval ≥ 470 ms.
- Any medical contraindication to treatment with chemotherapy as listed in the local labelling.
- Participants with moderate or severe cardiovascular disease.
- Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study interventions.
- Prior exposure to approved or investigational immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-TIGIT (T cell immunoreceptor with Ig and ITIM domains), anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies. Participants who received agents targeting the adenosine pathway, anti-NKG2A, anti-HLA-E agents, and anti-LIF agents are also excluded. Participants who have received previous treatment with a TROP2 targeting ADC or with another ADC containing a chemotherapy agent that inhibits TOP1 activity are also excluded.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of study interventions.
- Active or uncontrolled infections including HBA, HBV, HCV, and HIV.
Trial locations and contacts
97 sites in 12 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
97 sites in 12 countries
United States25 sites, 17 recruiting
- Withdrawn
Research Site
Baltimore, Maryland, 21201
- Recruiting
Research Site
Baltimore, Maryland, 21231
- Recruiting
Research Site
Boston, Massachusetts, 02215
- Withdrawn
Research Site
Buffalo, New York, 14263
- Recruiting
Research Site
Chattanooga, Tennessee, 37404
- Recruiting
Research Site
Chicago, Illinois, 60637
- Recruiting
Research Site
Cleveland, Ohio, 44195
- Recruiting
Research Site
Edmonds, Washington, 98026
- Recruiting
Research Site
Fairfax, Virginia, 22031
- Withdrawn
Research Site
Gainesville, Georgia, 30501
- Recruiting
Research Site
Houston, Texas, 77030
- Terminated
Research Site
Houston, Texas, 77090
- Recruiting
Research Site
Little Rock, Arkansas, 72205
- Recruiting
Research Site
Los Angeles, California, 90095
- Recruiting
Research Site
Memphis, Tennessee, 38120
- Withdrawn
Research Site
Nashville, Tennessee, 37203
- Recruiting
Research Site
Nashville, Tennessee, 37203
- Recruiting
Research Site
Nashville, Tennessee, 37232
- Recruiting
Research Site
New Haven, Connecticut, 06510
- Withdrawn
Research Site
Oakland, California, 94611
- Recruiting
Research Site
Omaha, Nebraska, 68124
- Recruiting
Research Site
Pittsburgh, Pennsylvania, 15212
- Completed
Research Site
Saint Louis Park, Minnesota, 55426
- Recruiting
Research Site
Seattle, Washington, 98104
- Completed
Research Site
Stuart, Florida, 34994
Italy13 sites, 12 recruiting
- Recruiting
Research Site
Aviano, 33081
- Recruiting
Research Site
Brescia, 25123
- Withdrawn
Research Site
Catanzaro, 88100
- Recruiting
Research Site
Florence, 50134
- Recruiting
Research Site
Genova, 16100
- Recruiting
Research Site
Meldola, 47014
- Recruiting
Research Site
Milan, 20162
- Recruiting
Research Site
Monza, 20900
- Recruiting
Research Site
Padova, 35128
- Recruiting
Research Site
Perugia, 06156
- Recruiting
Research Site
Pisa, 56124
- Recruiting
Research Site
Roma, 00144
- Recruiting
Research Site
Rozzano, 20089
Spain12 sites, 11 recruiting
- Recruiting
Research Site
A Coruña, 15006
- Recruiting
Research Site
Alicante, 03010
- Recruiting
Research Site
Barcelona, 08036
- Terminated
Research Site
Barcelona, 8035
- Recruiting
Research Site
Córdoba, 14004
- Recruiting
Research Site
Madrid, 28040
- Recruiting
Research Site
Majadahonda, 28250
- Recruiting
Research Site
Málaga, 29010
- Recruiting
Research Site
Reus, 43204
- Recruiting
Research Site
Seville, 41009
- Recruiting
Research Site
Terrassa, 08221
- Recruiting
Research Site
Valencia, 46010
France8 sites, 6 recruiting
- Recruiting
Research Site
Avignon, 84902
- Withdrawn
Research Site
Bobigny, 93009
- Recruiting
Research Site
Bordeaux, 33076
- Recruiting
Research Site
Limoges, 83000
- Recruiting
Research Site
Rennes, 35000
- Recruiting
Research Site
Rouen, 76031
- Recruiting
Research Site
Suresnes, 92150
- Active, not recruiting
Research Site
Toulon, 83000
Portugal7 sites, 5 recruiting
- Recruiting
Research Site
Lisbon, 1099-023
- Recruiting
Research Site
Lisbon, 1169-050
- Recruiting
Research Site
Lisbon, 1400-038
- Recruiting
Research Site
Lisbon, 1500-650
- Withdrawn
Research Site
Porto, 4099-001
- Completed
Research Site
Porto, 4100-180
- Recruiting
Research Site
Porto, 4200-072
South Korea7 sites, 5 recruiting
- Completed
Research Site
Busan, 48108
- Withdrawn
Research Site
Chungcheongbuk-do, 28644
- Recruiting
Research Site
Seongnam-si, 13496
- Recruiting
Research Site
Seoul, 03080
- Recruiting
Research Site
Seoul, 05505
- Recruiting
Research Site
Suwon, 16247
- Recruiting
Research Site
Suwon, 440-746
Taiwan5 sites, 5 recruiting
- Recruiting
Research Site
Liuying, 736
- Recruiting
Research Site
New Taipei City, 235
- Recruiting
Research Site
Tainan, 70403
- Recruiting
Research Site
Taipei, 10002
- Recruiting
Research Site
Taipei, 11217
Turkey (Türkiye)5 sites, 5 recruiting
- Recruiting
Research Site
Ankara, 06010
- Recruiting
Research Site
Ankara, 06500
- Recruiting
Research Site
Ankara, 06800
- Recruiting
Research Site
Istanbul, 34722
- Recruiting
Research Site
Izmir, 35575
Canada4 sites, 3 recruiting
- Completed
Research Site
Edmonton, Alberta, T6G 1Z2
- Recruiting
Research Site
Montreal, Quebec, H2W 1S6
- Recruiting
Research Site
Montreal, Quebec, H2X 3E4
- Recruiting
Research Site
Winnipeg, Manitoba, R3E 0V9
Hungary4 sites, 3 recruiting
- Recruiting
Research Site
Kecskemét, 6000
- Recruiting
Research Site
Székesfehérvár, 8000
- Completed
Research Site
Tatabánya, 2800
- Recruiting
Research Site
Törökbálint, 2045
Ireland4 sites, 4 recruiting
- Recruiting
Research Site
Dublin, D07 R2WY
- Recruiting
Research Site
Dublin, D08 NHY1
- Recruiting
Research Site
Dublin, D09 V2N0
- Recruiting
Research Site
Galway, H91 YR71
Belgium3 sites, 2 recruiting
- Recruiting
Research Site
Ghent, 9000
- Completed
Research Site
Ghent, 9000
- Recruiting
Research Site
Roeselare, 8800
About this study
Official title: A Phase II, Open-label, Multicentre, Randomised Study of Neoadjuvant and Adjuvant Treatment in Patients With Resectable, Early-stage (II to IIIB) Non-small Cell Lung Cancer (NeoCOAST-2)
The study is intended to assess the safety and efficacy of perioperative treatment with Durvalumab in combination with Oleclumab, Monalizumab, or AZD0171 and platinum doublet chemotherapy (CTX); or Volrustomig or Rilvegostomig in combination with CTX; or Datopotamab deruxtecan (Dato-DXd) in combination with Durvalumab or Rilvegostomig and single agent platinum chemotherapy in participants with resectable, early-stage non-small cell lung cancer.
Read the detailed description
This is an open-label, multi-arms, multicentre, randomised study, eligible participants will be enrolled and randomised to one of the following treatment regimens.
Arm 1: Participants will receive Oleclumab + durvalumab + CTX as neoadjuvant treatment and Oleclumab + durvalumab as adjuvant treatment.
Arm 2: Participants will receive Monalizumab + durvalumab + CTX as neoadjuvant treatment and Monalizumab + durvalumab as adjuvant treatment.
Arm 3: Participants will receive Volrustomig (Dose Exploration) + CTX as neoadjuvant treatment and Volrustomig as adjuvant treatment.
Arm 4: Participants will receive Dato-DXd + durvalumab + single agent platinum chemotherapy as neoadjuvant treatment and durvalumab as adjuvant treatment.
Arm 5: Participants will receive AZD0171 + durvalumab + CTX as neoadjuvant treatment and AZD0171 + durvalumab as adjuvant treatment.
Arm 6: Participants will receive Rilvegostomig + CTX as neoadjuvant treatment and Rilvegostomig as adjuvant treatment.
Arm 7: Participants will receive Dato-DXd + Rilvegostomig + single agent platinum chemotherapy as neoadjuvant treatment and Rilvegostomig as adjuvant treatment.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Durvalumab, Oleclumab, Monalizumab, Dato-DXd, AZD0171
- Keywords
- Lung Cancer, early-stage, Durvalumab, Oleclumab, Monalizumab, AZD0171, Datopotamab Deruxtecan, Neoadjuvant, Adjuvant, Chemotherapy, Volrustomig, Rilvegostomig
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736, IMFINZI
Participants will receive Durvalumab via intravenous route.
OleclumabDrug
Also called MEDI9447
Participants will receive Oleclumab via intravenous route.
MonalizumabDrug
Also called IPH2201
Participants will receive Monalizumab via intravenous route.
Dato-DXdDrug
Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.
AZD0171Drug
Participants will receive AZD0171 via intravenous route.
CarboplatinDrug
Carboplatin as chemotherapy
CisplatinDrug
Cisplatin as chemotherapy
Pemetrexed/CisplatinDrug
Pemetrexed/Cisplatin as chemotherapy
Pemetrexed/CarboplatinDrug
Pemetrexed/Carboplatin as chemotherapy
Carboplatin/PaclitaxelDrug
Carboplatin/Paclitaxel, as chemotherapy
VolrustomigDrug
Also called MEDI5752
Participants will receive Volrustomig via intravenous route.
RilvegostomigDrug
Participants will receive Rilvegostomig via intravenous route.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Oleclumab + Durvalumab + Platinum doublet chemotherapy (CTX) | Experimental | Participants will receive Durvalumab + Oleclumab + CTX as neoadjuvant treatment and Durvalumab + Oleclumab as adjuvant treatment.
Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:
Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin Receives: Drug: Durvalumab; Drug: Oleclumab; Drug: Pemetrexed/Cisplatin; Drug: Pemetrexed/Carboplatin; Drug: Carboplatin/Paclitaxel |
| Arm 2: Monalizumab + Durvalumab + CTX | Experimental | Participants will receive Durvalumab + Monalizumab + CTX as neoadjuvant treatment and Durvalumab + Monalizumab as adjuvant treatment.
Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:
Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin Receives: Drug: Durvalumab; Drug: Monalizumab; Drug: Pemetrexed/Cisplatin; Drug: Pemetrexed/Carboplatin; Drug: Carboplatin/Paclitaxel |
| Arm 3: Volrustomig (Dose Exploration) + CTX | Experimental | Participants will receive Volrustomig + CTX as neoadjuvant treatment and Volrustomig as adjuvant treatment.
Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:
Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin Receives: Drug: Pemetrexed/Cisplatin; Drug: Pemetrexed/Carboplatin; Drug: Carboplatin/Paclitaxel; Drug: Volrustomig |
| Arm 4: Dato-DXd + durvalumab + single agent platinum | Experimental | Participants will receive Dato-DXd + durvalumab + single agent platinum as neoadjuvant treatment and durvalumab as adjuvant treatment.
Participants will receive one of the following chemotherapy regimens, based on physician choice of as part of their treatment regimen prior to surgery:
Carboplatin or Cisplatin Receives: Drug: Durvalumab; Drug: Dato-DXd; Drug: Carboplatin; Drug: Cisplatin |
| Arm 5: AZD0171 + durvalumab + CTX | Experimental | Participants will receive AZD0171 + durvalumab + CTX as neoadjuvant treatment and AZD0171 + durvalumab as adjuvant treatment.
Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:
Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin Receives: Drug: Durvalumab; Drug: AZD0171; Drug: Pemetrexed/Cisplatin; Drug: Pemetrexed/Carboplatin; Drug: Carboplatin/Paclitaxel |
| Arm 6: Rilvegostomig + CTX | Experimental | Participants will receive Rilvegostomig + CTX as neoadjuvant treatment and Rilvegostomig as adjuvant treatment.
Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery:
Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin Receives: Drug: Pemetrexed/Cisplatin; Drug: Pemetrexed/Carboplatin; Drug: Carboplatin/Paclitaxel; Drug: Rilvegostomig |
| Arm 7: Dato-DXd + Rilvegostomig + single agent platinum | Experimental | Participants will receive Dato-DXd + Rilvegostomig + single agent platinum as neoadjuvant treatment and Rilvegostomig as adjuvant treatment.
Participants will receive one of the following chemotherapy regimens, based on physician choice of as part of their treatment regimen prior to surgery:
Carboplatin or Cisplatin Receives: Drug: Dato-DXd; Drug: Carboplatin; Drug: Cisplatin; Drug: Rilvegostomig |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with pathological complete response (pCR)
Measured: From randomization to approximately 15 weeks after the first dose of study interventions
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Measured: Until Day 90 after the last dose of study interventions (Up to approximately 3 years)
Secondary outcomes (10)
Number of participants experiencing an event-free survival (EFS) event
Measured: Up to approximately 3 years
Number of participants experiencing a disease-free survival (DFS) event
Measured: Up to approximately 3 years
Number of participants having surgical resection
Measured: From randomization to approximately 15 weeks after the first dose of study interventions
Number of participants with major pathological response (mPR)
Measured: From randomization to approximately 15 weeks after the first dose of study interventions
Number of participants with Objective response rate (ORR)
Measured: From randomization to approximately 15 weeks after the first dose of study interventions
Overall survival (OS)
Measured: Up to approximately 3 years
Serum concentration of study interventions (Durvalumab/Oleclumab/Monalizumab/Volrustomig/Rilvegostomig)
Measured: From randomization to last dose of study interventions (Up to approximately 3 Years)
Number of participants with anti-study drug antibodies (ADA)
Measured: From randomization to 3 months after last dose of study interventions (Up to approximately 3 Years)
Baseline PD-L1 expression
Measured: At Screening/ baseline
Changes in circulating tumour DNA (ctDNA)
Measured: From randomization to up to 24 months after last dose of study interventions (Up to approximately 3 Years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2021
- Study start14 Apr 2022
- Primary completion28 May 2030 (estimated)
- Study completion28 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 630 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Tina Cascone, MD, Principal investigator, MD Anderson Cancer Center Houston, TX 77030
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05061550
- Sponsor's protocol ID
- D9077C00001
- Other IDs
- 2023-508852-21-00, 2021-003369-37, 2023
- Acronym
- NeoCOAST-2
- Status last verified
- Oct 2026
- First submitted
- 20 Sep 2021
- Last updated
- 21 Oct 2026
- Results posted
- No
- 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 Vivli.org. All requests 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 approved.
Publications
Cascone T, Bonanno L, Guisier F, Insa A, Liberman M, Bylicki O, Livi L, Egenod T, Corre R, Kim DW, Garcia Campelo MR, Provencio Pulla M, Shim BY, Metro G, Bennouna J, Bielska AA, Yohannes AR, He Y, Dowson A, Kar G, McGrath L, Kumar R, Grenga I, Spicer J, Forde PM. Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: the platform phase 2 NeoCOAST-2 trial. Nat Med. 2025 Aug;31(8):2788-2796. doi: 10.1038/s41591-025-03746-z. Epub 2025 May 31.
PubMed 40450142