Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer (NeoCOAST-2)

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Cisplatin; Drug: Rilvegostomig; Drug: Dato-DXd; Drug: Volrustomig; Drug: Carboplatin/Paclitaxel; Drug: Carboplatin; Drug: Pemetrexed/Carboplatin; Drug: Durvalumab; Drug: Pemetrexed/Cisplatin; Drug: AZD0171; Drug: Monalizumab; Drug: Oleclumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05061550

2023-508852-21-00 (Other Identifier)

D9077C00001

2021-003369-37 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 630 estimated patients

Sex: All

Ages: 18 to 95 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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630 participants in 7 patient groups

Arm 1: Oleclumab + Durvalumab + Platinum doublet chemotherapy (CTX)

Experimental group

Description:

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

Treatment:

Drug: Oleclumab

Drug: Pemetrexed/Cisplatin

Drug: Pemetrexed/Carboplatin

Drug: Durvalumab

Drug: Carboplatin/Paclitaxel

Arm 2: Monalizumab + Durvalumab + CTX

Experimental group

Description:

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

Treatment:

Drug: Monalizumab

Drug: Pemetrexed/Cisplatin

Drug: Pemetrexed/Carboplatin

Drug: Durvalumab

Drug: Carboplatin/Paclitaxel

Arm 3: Volrustomig (Dose Exploration) + CTX

Experimental group

Description:

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

Treatment:

Drug: Volrustomig

Drug: Pemetrexed/Cisplatin

Drug: Pemetrexed/Carboplatin

Drug: Carboplatin/Paclitaxel

Arm 4: Dato-DXd + durvalumab + single agent platinum

Experimental group

Description:

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

Treatment:

Drug: Dato-DXd

Drug: Durvalumab

Drug: Carboplatin

Drug: Cisplatin

Arm 5: AZD0171 + durvalumab + CTX

Experimental group

Description:

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

Treatment:

Drug: AZD0171

Drug: Pemetrexed/Cisplatin

Drug: Pemetrexed/Carboplatin

Drug: Durvalumab

Drug: Carboplatin/Paclitaxel

Arm 6: Rilvegostomig + CTX

Experimental group

Description:

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

Treatment:

Drug: Pemetrexed/Cisplatin

Drug: Pemetrexed/Carboplatin

Drug: Rilvegostomig

Drug: Carboplatin/Paclitaxel

Arm 7: Dato-DXd + Rilvegostomig + single agent platinum

Experimental group

Description:

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

Treatment:

Drug: Dato-DXd

Drug: Carboplatin

Drug: Rilvegostomig

Drug: Cisplatin