Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer

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)

Overview

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.

Interventions

• Drug Durvalumab
  Participants will receive Durvalumab via intravenous route.
• Drug Oleclumab
  Participants will receive Oleclumab via intravenous route.
• Drug Monalizumab
  Participants will receive Monalizumab via intravenous route.
• Drug Dato-DXd
  Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.
• Drug AZD0171
  Participants will receive AZD0171 via intravenous route.
• Drug Carboplatin
  Carboplatin as chemotherapy
• Drug Cisplatin
  Cisplatin as chemotherapy
• Drug Pemetrexed/Cisplatin
  Pemetrexed/Cisplatin as chemotherapy
• Drug Pemetrexed/Carboplatin
  Pemetrexed/Carboplatin as chemotherapy
• Drug Carboplatin/Paclitaxel
  Carboplatin/Paclitaxel, as chemotherapy

Primary outcome measures

• 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 outcome measures (10)

• 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

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 25 centers

• Research Site — Little Rock
• Research Site — Los Angeles
• Research Site — Oakland
• Research Site — New Haven
• Research Site — Stuart
• Research Site — Gainesville
• Research Site — Chicago
• Research Site — Baltimore
• … and 17 more centers

Italy · 13 centers

• Research Site — Aviano
• Research Site — Brescia
• Research Site — Catanzaro
• Research Site — Florence
• Research Site — Genova
• Research Site — Meldola
• Research Site — Milan
• Research Site — Monza
• … and 5 more centers

Spain · 12 centers

• Research Site — A Coruña
• Research Site — Alicante
• Research Site — Barcelona
• Research Site — Barcelona
• Research Site — Córdoba
• … and 7 more centers

France · 8 centers

• Research Site — Avignon
• Research Site — Bobigny
• Research Site — Bordeaux
• Research Site — Limoges
• Research Site — Rennes
• Research Site — Rouen
• Research Site — Suresnes
• Research Site — Toulon

Portugal · 7 centers

• Research Site — Lisbon
• Research Site — Lisbon
• Research Site — Lisbon
• Research Site — Lisbon
• Research Site — Porto
• Research Site — Porto
• Research Site — Porto

South Korea · 7 centers

• Research Site — Busan
• Research Site — Chungcheongbuk-do
• Research Site — Seongnam-si
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Suwon
• Research Site — Suwon

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 5 centers

Center list to be confirmed — check the primary protocol.

Canada · 4 centers

• Research Site — Edmonton
• Research Site — Winnipeg
• Research Site — Montreal
• Research Site — Montreal

Hungary · 4 centers

• Research Site — Kecskemét
• Research Site — Székesfehérvár
• Research Site — Tatabánya
• Research Site — Törökbálint

Ireland · 4 centers

• Research Site — Dublin
• Research Site — Dublin
• Research Site — Dublin
• Research Site — Galway

Belgium · 3 centers

• Research Site — Ghent
• Research Site — Ghent
• Research Site — Roeselare

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 t PMID 40450142

Identifiers

NCT: NCT05061550 · D9077C00001 · 2023-508852-21-00 · 2021-003369-37

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗