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

• ClinicalTrials.gov Identifier: NCT05061550
• Recruitment Status: Recruiting
• First Posted: September 29, 2021
• Last Update Posted: May 13, 2024
• Sponsor: AstraZeneca
• Collaborator: Parexel
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: September 20, 2021
• First Posted Date: September 29, 2021
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: April 14, 2022
• Estimated Primary Completion Date: December 22, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2022)

• 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) ]

Original Primary Outcome Measures (submitted: September 20, 2021)

• Number of participants with pathological complete response (pCR) [ Time Frame: Within 40 days of the last dose of study drug after cycle 4 (each cycle length is 21 days) (Up to approximately 3 Years) ]
  pCR is determined by central blinded independent pathologist review (BIPR) and described by International Association for the Study of Lung Cancer (IASLC) 2020.
• Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Untill Day 90 after the last dose of study drugs (Up to approximately 3 years) ]
  To assess safety and tolerability.

Current Secondary Outcome Measures (submitted: February 14, 2024)

• 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) [ 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) ]

Original Secondary Outcome Measures (submitted: September 20, 2021)

• Number of participants experiencing an event-free survival (EFS) event [ Time Frame: Up to approximately 3 years ]
  Assessments of EFS will be done by investigator.
• Number of participants experiencing a disease-free survival (DFS) event [ Time Frame: Up to approximately 3 years ]
  Assessments of DFS will be done by investigator.
• Number of participants having surgical resection [ Time Frame: Within 40 days of the last dose of study drug after cycle 4 (each cycle length is 21 days) (Up to approximately 3 Years) ]
  Feasibility to surgery is defined as having the planned surgical resection within 40 days from the end of the last dose of neoadjuvant study drugs.
• Number of participants with major pathological response (mPR) [ Time Frame: Within 40 days of the last dose of study drug after cycle 4 (each cycle length is 21 days) (Up to approximately 3 Years) ]
  mPR is determined by central BIPR as described by IASLC 2020.
• Number of participants with Objective response rate (ORR) [ Time Frame: Up to approximately 3 years ]
  Assessments of ORR will be done by investigator.
• Overall survival (OS) [ Time Frame: Up to approximately 3 years ]
  Assessments of OS will be done by investigator.
• Serum concentration of study drugs (Durvalumab/Oleclumab/Monalizumab) [ Time Frame: Pre-dose and post-dose of cycle 1 to 4 (21 days cycle) and cycle 1 to 12 (28 days cycle) ]
  To measure the concentration of Durvalumab/Oleclumab/Monalizumab in serum as variable of pharmacokinetic parameter.
• Number of participants with anti-study drug antibodies (ADA) [ Time Frame: Pre-dose and post-dose of cycle 1 to 4 (21 days cycle) and cycle 1 to 12 (28 days cycle) ]
  To assess the presence of anti-drug antibody (ADA) for study drugs (Durvalumab/Oleclumab/Monalizumab) as variable of immunogenicity parameters.
• Baseline PD-L1 expression [ Time Frame: At Screening/ baseline ]
  The baseline PD-L1 expression in participants treated with neoadjuvant and adjuvant treatment, and associations with clinical endpoints will be investigated.
• Changes in circulating tumour DNA (ctDNA) [ Time Frame: Pre-dose and post-dose of cycle 1 to 4 (21 days cycle) and cycle 1 to 12 (28 days cycle) ]
  The changes in ctDNA during neoadjuvant treatment in participants with evaluable ctDNA and associations with clinical endpoints will be evaluated.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Brief 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 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.

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• Drug: Durvalumab
  Participants will receive Durvalumab via intravenous route.
  Other Name: MEDI4736, IMFINZI
• Drug: Oleclumab
  Participants will receive Oleclumab via intravenous route.
  Other Name: MEDI9447
• Drug: Monalizumab
  Participants will receive Monalizumab via intravenous route.
  Other Name: IPH2201
• 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
• Drug: Volrustomig
  Participants will receive Volrustomig via intravenous route.
  Other Name: MEDI5752

Study Arms

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

  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

  Interventions:

  • Drug: Durvalumab
  • Drug: Oleclumab
  • Drug: Pemetrexed/Cisplatin
  • Drug: Pemetrexed/Carboplatin
  • Drug: Carboplatin/Paclitaxel
• Experimental: Arm 2: Monalizumab + Durvalumab + CTX

  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

  Interventions:

  • Drug: Durvalumab
  • Drug: Monalizumab
  • Drug: Pemetrexed/Cisplatin
  • Drug: Pemetrexed/Carboplatin
  • Drug: Carboplatin/Paclitaxel
• Experimental: Arm 3: Volrustomig (Dose Exploration) + CTX

  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

  Interventions:

  • Drug: Pemetrexed/Cisplatin
  • Drug: Pemetrexed/Carboplatin
  • Drug: Carboplatin/Paclitaxel
  • Drug: Volrustomig
• Experimental: Arm 4: Dato-DXd + durvalumab + single agent platinum

  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

  Interventions:

  • Drug: Durvalumab
  • Drug: Dato-DXd
  • Drug: Carboplatin
  • Drug: Cisplatin
• Experimental: Arm 5: AZD0171 + durvalumab + CTX

  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

  Interventions:

  • Drug: Durvalumab
  • Drug: AZD0171
  • Drug: Pemetrexed/Cisplatin
  • Drug: Pemetrexed/Carboplatin
  • Drug: Carboplatin/Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 14, 2024): 490
• Original Estimated Enrollment (submitted: September 20, 2021): 140
• Estimated Study Completion Date: December 22, 2028
• Estimated Primary Completion Date: December 22, 2028 (Final data collection date for primary outcome measure)

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.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 95 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: Belgium, Canada, France, Hungary, Ireland, Italy, Korea, Republic of, Portugal, Spain, Taiwan, Turkey, United States

Administrative Information

• NCT Number: NCT05061550
• Other Study ID Numbers: D9077C00001; 2023-508852-21-00 ( Other Identifier: EU CT Number ); 2021-003369-37 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

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 Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• URL: https://vivli.org/

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Parexel

Investigators

• Principal Investigator: Tina Cascone, MD; MD Anderson Cancer Center Houston, TX 77030

• PRS Account: AstraZeneca
• Verification Date: May 2024