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)
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 or Rilvegostomig and single agent platinum chemotherapy in participants with resectable, early-stage non-small cell lung cancer.
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.
Arms & interventions
- DrugDurvalumab
Participants will receive Durvalumab via intravenous route.
- DrugOleclumab
Participants will receive Oleclumab via intravenous route.
- DrugMonalizumab
Participants will receive Monalizumab via intravenous route.
- DrugDato-DXd
Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.
- DrugAZD0171
Participants will receive AZD0171 via intravenous route.
- DrugCarboplatin
Carboplatin as chemotherapy
- DrugCisplatin
Cisplatin as chemotherapy
- DrugPemetrexed/Cisplatin
Pemetrexed/Cisplatin as chemotherapy
- DrugPemetrexed/Carboplatin
Pemetrexed/Carboplatin as chemotherapy
- DrugCarboplatin/Paclitaxel
Carboplatin/Paclitaxel, as chemotherapy
- DrugVolrustomig
Participants will receive Volrustomig via intravenous route.
- DrugRilvegostomig
Participants will receive Rilvegostomig via intravenous route.
Outcome measures
Primary
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)
Secondary
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)
Eligibility criteria
Study locations (25)
Research Site
Little Rock, Arkansas, 72205
Research Site
Los Angeles, California, 90095
Research Site
Oakland, California, 94611
Research Site
New Haven, Connecticut, 06510
Research Site
Stuart, Florida, 34994
Research Site
Gainesville, Georgia, 30501
Research Site
Chicago, Illinois, 60637
Research Site
Baltimore, Maryland, 21201
Research Site
Baltimore, Maryland, 21231
Research Site
Boston, Massachusetts, 02215
Research Site
Saint Louis Park, Minnesota, 55426
Research Site
Omaha, Nebraska, 68124
Research Site
Buffalo, New York, 14263
Research Site
Cleveland, Ohio, 44195
Research Site
Pittsburgh, Pennsylvania, 15212
Research Site
Chattanooga, Tennessee, 37404
Research Site
Memphis, Tennessee, 38120
Research Site
Nashville, Tennessee, 37203
Research Site
Nashville, Tennessee, 37203
Research Site
Nashville, Tennessee, 37232
Research Site
Houston, Texas, 77030
Research Site
Houston, Texas, 77090
Research Site
Fairfax, Virginia, 22031
Research Site
Edmonds, Washington, 98026
Research Site
Seattle, Washington, 98104
References
- 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)