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

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AstraZeneca

Status and phase

Enrolling
Phase 2

Conditions

Non-small Cell Lung Cancer

Treatments

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

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 in combination with platinum doublet chemotherapy or datopotamab deruxtecan (Dato-DXd) in combination with durvalumab 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.

Enrollment

490 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.
  • 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 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-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)

490 participants in 5 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: Pemetrexed/Cisplatin
Drug: Pemetrexed/Carboplatin
Drug: Carboplatin/Paclitaxel
Drug: Oleclumab
Drug: Durvalumab
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: Pemetrexed/Cisplatin
Drug: Monalizumab
Drug: Pemetrexed/Carboplatin
Drug: Carboplatin/Paclitaxel
Drug: Durvalumab
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: Pemetrexed/Cisplatin
Drug: Volrustomig
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: Carboplatin
Drug: Cisplatin
Drug: Durvalumab
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: Pemetrexed/Cisplatin
Drug: Pemetrexed/Carboplatin
Drug: Carboplatin/Paclitaxel
Drug: AZD0171
Drug: Durvalumab

Trial contacts and locations

95

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Central trial contact

AstraZeneca Clinical Study Information Center

Data sourced from clinicaltrials.gov

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