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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Drug: Oleclumab; Drug: Carboplatin/Paclitaxel; Drug: Pemetrexed/Cisplatin; Drug: Pemetrexed/Carboplatin; Drug: Monalizumab; Drug: Dato-DXd; Drug: Carboplatin; Drug: Cisplatin; Drug: AZD0171; Drug: Volrustomig

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
• Enrollment (Estimated): 490
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Belgium
  • Charleroi, Belgium, 6000
    • Recruiting
    • Research Site
  • Gent, Belgium, 9000
    • Recruiting
    • Research Site
  • Gent, Belgium, 9000
    • Completed
    • Research Site
  • Leuven, Belgium, 3000
    • Completed
    • Research Site
  • Roeselare, Belgium, 8800
    • Recruiting
    • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Completed
      • Research Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Not yet recruiting
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Completed
      • Research Site
    • Montréal, Quebec, Canada, H2W 1S6
      • Recruiting
      • Research Site
• France
  • Avignon Cedex, France, 84902
    • Recruiting
    • Research Site
  • Bobigny, France, 93009
    • Withdrawn
    • Research Site
  • Bordeaux Cedex, France, 33076
    • Completed
    • Research Site
  • Limoges, France, 83000
    • Completed
    • Research Site
  • Rennes Cedex, France, 35000
    • Recruiting
    • Research Site
  • Rouen, France, 76031
    • Completed
    • Research Site
  • Suresnes, France, 92150
    • Recruiting
    • Research Site
  • Toulon, France, 83000
    • Recruiting
    • Research Site
• Hungary
  • Kecskemét, Hungary, 6000
    • Recruiting
    • Research Site
  • Székesfehérvár, Hungary, 8000
    • Recruiting
    • Research Site
  • Tatabánya, Hungary, 2800
    • Recruiting
    • Research Site
  • Törökbálint, Hungary, 2045
    • Recruiting
    • Research Site
• Ireland
  • Dublin, Ireland, D09 V2N0
    • Recruiting
    • Research Site
  • Dublin 7, Ireland, D07 R2WY
    • Completed
    • Research Site
  • Dublin 8, Ireland, D08 NHY1
    • Recruiting
    • Research Site
  • Galway, Ireland, H91 YR71
    • Recruiting
    • Research Site
• Italy
  • Aviano, Italy, 33081
    • Recruiting
    • Research Site
  • Brescia, Italy, 25123
    • Recruiting
    • Research Site
  • Catanzaro, Italy, 88100
    • Withdrawn
    • Research Site
  • Firenze, Italy, 50134
    • Completed
    • Research Site
  • Genova, Italy, 16100
    • Recruiting
    • Research Site
  • Meldola, Italy, 47014
    • Recruiting
    • Research Site
  • Milano, Italy, 20162
    • Recruiting
    • Research Site
  • Monza, Italy, 20900
    • Completed
    • Research Site
  • Padova, Italy, 35128
    • Recruiting
    • Research Site
  • Perugia, Italy, 06156
    • Recruiting
    • Research Site
  • Pisa, Italy, 56124
    • Recruiting
    • Research Site
  • Roma, Italy, 00144
    • Completed
    • Research Site
  • Rozzano, Italy, 20089
    • Recruiting
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 48108
    • Recruiting
    • Research Site
  • Chungcheongbuk-do, Korea, Republic of, 28644
    • Withdrawn
    • Research Site
  • Seongnam-si, Korea, Republic of, 13496
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Completed
    • Research Site
  • Suwon, Korea, Republic of, 16247
    • Recruiting
    • Research Site
  • Suwon, Korea, Republic of, 440-746
    • Recruiting
    • Research Site
• Portugal
  • Lisboa, Portugal, 1400-038
    • Recruiting
    • Research Site
  • Lisboa, Portugal, 1500-650
    • Recruiting
    • Research Site
  • Lisboa, Portugal, 1099-023
    • Completed
    • Research Site
  • Lisbon, Portugal, 1169-050
    • Recruiting
    • Research Site
  • Porto, Portugal, 4200-072
    • Recruiting
    • Research Site
  • Porto, Portugal, 4100-180
    • Recruiting
    • Research Site
  • Porto, Portugal, 4099-001
    • Withdrawn
    • Research Site
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Research Site
  • Barcelona, Spain, 08036
    • Recruiting
    • Research Site
  • Barcelona, Spain, 8035
    • Recruiting
    • Research Site
  • Cordoba, Spain, 14004
    • Completed
    • Research Site
  • Coruña, Spain, 15006
    • Recruiting
    • Research Site
  • Madrid, Spain, 28040
    • Recruiting
    • Research Site
  • Majadahonda, Spain, 28250
    • Recruiting
    • Research Site
  • Malaga, Spain, 29010
    • Recruiting
    • Research Site
  • Reus,Tarragona, Spain, 43204
    • Recruiting
    • Research Site
  • Sevilla, Spain, 41009
    • Recruiting
    • Research Site
  • Terrassa, Spain, 08221
    • Recruiting
    • Research Site
  • Valencia, Spain, 46010
    • Recruiting
    • Research Site
• Taiwan
  • Liuying, Taiwan, 736
    • Recruiting
    • Research Site
  • Tainan City, Taiwan, 70403
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 10002
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 235
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 11217
    • Recruiting
    • Research Site
• Turkey
  • Ankara, Turkey, 06010
    • Recruiting
    • Research Site
  • Ankara, Turkey, 06800
    • Recruiting
    • Research Site
  • Ankara, Turkey, 06500
    • Recruiting
    • Research Site
  • Istanbul, Turkey, 34722
    • Recruiting
    • Research Site
  • Izmir, Turkey, 35575
    • Not yet recruiting
    • Research Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • Research Site
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Research Site
    • Oakland, California, United States, 94611
      • Withdrawn
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Research Site
  • Florida
    • Stuart, Florida, United States, 34994
      • Recruiting
      • Research Site
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Completed
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Research Site
    • Baltimore, Maryland, United States, 21201
      • Withdrawn
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Research Site
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
      • Recruiting
      • Research Site
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • Research Site
    • Memphis, Tennessee, United States, 38120
      • Recruiting
      • Research Site
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Research Site
    • Houston, Texas, United States, 77090
      • Recruiting
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Durvalumab; Participants will receive Durvalumab via intravenous route.; Other Names: MEDI4736, IMFINZI; Drug: Oleclumab; Participants will receive Oleclumab via intravenous route.; Other Names: MEDI9447; Drug: Carboplatin/Paclitaxel; Carboplatin/Paclitaxel, as chemotherapy; Drug: Pemetrexed/Cisplatin; Pemetrexed/Cisplatin as chemotherapy; Drug: Pemetrexed/Carboplatin; Pemetrexed/Carboplatin as chemotherapy
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	Drug: Durvalumab; Participants will receive Durvalumab via intravenous route.; Other Names: MEDI4736, IMFINZI; Drug: Carboplatin/Paclitaxel; Carboplatin/Paclitaxel, as chemotherapy; Drug: Pemetrexed/Cisplatin; Pemetrexed/Cisplatin as chemotherapy; Drug: Pemetrexed/Carboplatin; Pemetrexed/Carboplatin as chemotherapy; Drug: Monalizumab; Participants will receive Monalizumab via intravenous route.; Other Names: IPH2201
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	Drug: Carboplatin/Paclitaxel; Carboplatin/Paclitaxel, as chemotherapy; Drug: Pemetrexed/Cisplatin; Pemetrexed/Cisplatin as chemotherapy; Drug: Pemetrexed/Carboplatin; Pemetrexed/Carboplatin as chemotherapy; Drug: Volrustomig; Participants will receive Volrustomig via intravenous route.; Other Names: MEDI5752
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	Drug: Durvalumab; Participants will receive Durvalumab via intravenous route.; Other Names: MEDI4736, IMFINZI; Drug: Dato-DXd; Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.; Drug: Carboplatin; Carboplatin as chemotherapy; Drug: Cisplatin; Cisplatin as chemotherapy
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	Drug: Durvalumab; Participants will receive Durvalumab via intravenous route.; Other Names: MEDI4736, IMFINZI; Drug: Carboplatin/Paclitaxel; Carboplatin/Paclitaxel, as chemotherapy; Drug: Pemetrexed/Cisplatin; Pemetrexed/Cisplatin as chemotherapy; Drug: Pemetrexed/Carboplatin; Pemetrexed/Carboplatin as chemotherapy; Drug: AZD0171; Participants will receive AZD0171 via intravenous route.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with pathological complete response (pCR)	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)	Until Day 90 after the last dose of study interventions (Up to approximately 3 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants experiencing an event-free survival (EFS) event	Up to approximately 3 years
Number of participants experiencing a disease-free survival (DFS) event	Up to approximately 3 years
Number of participants having surgical resection	From randomization to approximately 15 weeks after the first dose of study interventions
Number of participants with major pathological response (mPR)	From randomization to approximately 15 weeks after the first dose of study interventions
Number of participants with Objective response rate (ORR)	From randomization to approximately 15 weeks after the first dose of study interventions
Overall survival (OS)	Up to approximately 3 years
Number of participants with anti-study drug antibodies (ADA)	From randomization to 3 months after last dose of study interventions (Up to approximately 3 Years)
Baseline PD-L1 expression	At Screening/ baseline
Changes in circulating tumour DNA (ctDNA)	From randomization to up to 24 months after last dose of study interventions (Up to approximately 3 Years)
Serum concentration of study interventions (Durvalumab/Oleclumab/Monalizumab/Volrustomig)	From randomization to last dose of study interventions (Up to approximately 3 Years)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel
• Investigators: Principal Investigator: Tina Cascone, MD, MD Anderson Cancer Center Houston, TX 77030

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Estimated): December 22, 2028
• Study Completion (Estimated): December 22, 2028

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: September 20, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Lung Cancer; Chemotherapy; Neoadjuvant; Adjuvant; Durvalumab; Datopotamab Deruxtecan; Oleclumab; early-stage; Monalizumab; AZD0171; Volrustomig
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Paclitaxel; Cisplatin; Durvalumab; Pemetrexed
• Other Study ID Numbers: D9077C00001; 2021-003369-37 (EudraCT Number); 2023-508852-21-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No