A Phase 2 interventional study of Durvalumab and Oleclumab in Non-small Cell Lung Cancer, sponsored by AstraZeneca. Recruiting at 97 sites in 12 countries. Open to participants aged 18 Years to 95 Years. Per ClinicalTrials.gov, last updated 2026-09-23.
Sponsored by AstraZeneca · Phase 2, Interventional, and Treatment
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.
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.
Exclusion Criteria:
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
Drug: Durvalumab · Drug: Oleclumab · Drug: Pemetrexed/Cisplatin · Drug: Pemetrexed/Carboplatin · Drug: Carboplatin/Paclitaxel
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
Drug: Durvalumab · Drug: Monalizumab · Drug: Pemetrexed/Cisplatin · Drug: Pemetrexed/Carboplatin · Drug: Carboplatin/Paclitaxel
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
Drug: Pemetrexed/Cisplatin · Drug: Pemetrexed/Carboplatin · Drug: Carboplatin/Paclitaxel · Drug: Volrustomig
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
Drug: Durvalumab · Drug: Dato-DXd · Drug: Carboplatin · Drug: Cisplatin
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
Drug: Durvalumab · Drug: AZD0171 · Drug: Pemetrexed/Cisplatin · Drug: Pemetrexed/Carboplatin · Drug: Carboplatin/Paclitaxel
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
Drug: Pemetrexed/Cisplatin · Drug: Pemetrexed/Carboplatin · Drug: Carboplatin/Paclitaxel · Drug: Rilvegostomig
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
Drug: Dato-DXd · Drug: Carboplatin · Drug: Cisplatin · Drug: Rilvegostomig
Participants will receive Durvalumab via intravenous route.
Also known as: MEDI4736, IMFINZI
Participants will receive Oleclumab via intravenous route.
Also known as: MEDI9447
Participants will receive Monalizumab via intravenous route.
Also known as: IPH2201
Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.
Participants will receive AZD0171 via intravenous route.
Carboplatin as chemotherapy
Cisplatin as chemotherapy
Pemetrexed/Cisplatin as chemotherapy
Pemetrexed/Carboplatin as chemotherapy
Carboplatin/Paclitaxel, as chemotherapy
Participants will receive Volrustomig via intravenous route.
Also known as: MEDI5752
Participants will receive Rilvegostomig via intravenous route.
Number of participants with pathological complete response (pCR)
Time frame: 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)
Time frame: Until Day 90 after the last dose of study interventions (Up to approximately 3 years)
Number of participants experiencing an event-free survival (EFS) event
Time frame: Up to approximately 3 years
Number of participants experiencing a disease-free survival (DFS) event
Time frame: Up to approximately 3 years
Number of participants having surgical resection
Time frame: From randomization to approximately 15 weeks after the first dose of study interventions
Number of participants with major pathological response (mPR)
Time frame: From randomization to approximately 15 weeks after the first dose of study interventions
Number of participants with Objective response rate (ORR)
Time frame: From randomization to approximately 15 weeks after the first dose of study interventions
Overall survival (OS)
Time frame: Up to approximately 3 years
Serum concentration of study interventions (Durvalumab/Oleclumab/Monalizumab/Volrustomig/Rilvegostomig)
Time frame: From randomization to last dose of study interventions (Up to approximately 3 Years)
Number of participants with anti-study drug antibodies (ADA)
Time frame: From randomization to 3 months after last dose of study interventions (Up to approximately 3 Years)
Baseline PD-L1 expression
Time frame: At Screening/ baseline
Changes in circulating tumour DNA (ctDNA)
Time frame: From randomization to up to 24 months after last dose of study interventions (Up to approximately 3 Years)
Plan to share: 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.
Supporting information: Study protocol, Sap
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Carcinoma, Non-Small-Cell Lung→
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