Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Resectable Non-Small Cell Lung Cancer
A Phase 2 Open-label, Multicenter, Randomized, Multidrug Platform Study of Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Subjects With Resectable, Early-stage (I [> 2 cm] to IIIA) Non-small Cell Lung Cancer (NeoCOAST)
1 other identifier
interventional
84
7 countries
18
Brief Summary
Study D9108C00002 (NeoCOAST) is a platform study assessing the effectiveness and safety of neoadjuvant durvalumab alone or in combination with novel agents in participants with resectable, early-stage (Stage I \[\>2cm\] to IIIA) non-small cell lung cancer (NSCLC).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2019
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 10, 2018
CompletedFirst Posted
Study publicly available on registry
January 7, 2019
CompletedStudy Start
First participant enrolled
March 8, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 13, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
January 13, 2021
CompletedResults Posted
Study results publicly available
February 24, 2022
CompletedFebruary 24, 2022
February 1, 2022
1.9 years
December 10, 2018
January 11, 2022
February 23, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Major Pathological Response Rate
Major pathological response rate is defined as percentage of participants with \<=10% residual viable tumor cells in the resected specimen.
Day 1 through Day 42
Secondary Outcomes (5)
Pathological Complete Response (pCR) Rate
Day 1 through Day 42
Feasibility to Surgery
Day 29 to Day 42 after Week 1 Day 1
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
From Day 1 through Day 105
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities
From Day 1 through Day 105
Number of Participants With Abnormal Vital Signs Reported as TEAEs
From Day 1 through Day 105
Study Arms (4)
Durvalumab 1500 mg
EXPERIMENTALParticipants will receive durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
Durvalumab 1500 mg + Oleclumab 3000 mg
EXPERIMENTALParticipants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
Durvalumab 1500 mg + Monalizumab 750 mg
EXPERIMENTALParticipants will receive durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
Durvalumab 1500 mg + Danvatirsen 200 mg
EXPERIMENTALParticipants will receive danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection will be planned between Day 29 and Day 42. After surgical resection, participants will be followed up to Day 105 (starting from Week 1 Day 1).
Interventions
Durvalumab 1500 mg IV will be administered Q4W (on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
Oleclumab 3000 mg IV will be administered Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
Monalizumab 750 mg IV will be administered Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
Danvatirsen 200 mg IV will be administered on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period) and later every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period.
Eligibility Criteria
You may qualify if:
- Cytologically and/or histologically-documented NSCLC
- Stage I (\> 2 cm) to IIIA (for participants with N2 disease, only those with 1 single nodal station ≤ 3 cm are eligible) NSCLC according to the 8th edition of American Joint Committee on Cancer staging classification
- Amenable to complete surgical resection
- Have not received any other therapy for this condition
- Predicted forced expiratory volume in one second (FEV1) ≥ 50%
- Predicted diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50%
- ECOG 0 or 1
- Adequate organ function
You may not qualify if:
- Participants with small-cell lung cancer or mixed small-cell lung cancer
- Participants who require or may require pneumonectomy
- Prior treatment with programmed cell death ligand-1 (PD-L1), PD-L1, or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors
- Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug.
- Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion:
- Participants with vitiligo or alopecia
- Participants with hypothyroidism on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Participants without active disease in the last 5 years may be included but only after consultation with the study physician
- Participants with celiac disease controlled by diet alone
- Pregnant or breast-feeding female
- Major surgical procedure within prior 30 days
- History of active primary immunodeficiency
- Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV
- QTc interval (QTc) ≥ 470 ms
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MedImmune LLClead
Study Sites (18)
Research Site
La Jolla, California, 92093, United States
Research Site
Fort Myers, Florida, 33901, United States
Research Site
Leesburg, Florida, 34748, United States
Research Site
Baltimore, Maryland, 21231, United States
Research Site
Buffalo, New York, 14263, United States
Research Site
New York, New York, 10016, United States
Research Site
Chattanooga, Tennessee, 37404, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Fairfax, Virginia, 22031, United States
Research Site
Montreal, Quebec, H4A 3J1, Canada
Research Site
Marseille, 13009, France
Research Site
Toulouse, 31059, France
Research Site
Orbassano, 10043, Italy
Research Site
Porto, 4200-072, Portugal
Research Site
A Coruña, 15001, Spain
Research Site
Barcelona, 08916, Spain
Research Site
Zurich, 8091, Switzerland
Related Publications (1)
Cascone T, Kar G, Spicer JD, Garcia-Campelo R, Weder W, Daniel DB, Spigel DR, Hussein M, Mazieres J, Oliveira J, Yau EH, Spira AI, Anagnostou V, Mager R, Hamid O, Cheng LY, Zheng Y, Blando J, Tan TH, Surace M, Rodriguez-Canales J, Gopalakrishnan V, Sellman BR, Grenga I, Soo-Hoo Y, Kumar R, McGrath L, Forde PM. Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial. Cancer Discov. 2023 Nov 1;13(11):2394-2411. doi: 10.1158/2159-8290.CD-23-0436.
PMID: 37707791DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The pharmacokinetic and immunogenicity samples are still being analyzed. Results for these outcome measures will be posted by 30Jun2022.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 10, 2018
First Posted
January 7, 2019
Study Start
March 8, 2019
Primary Completion
January 13, 2021
Study Completion
January 13, 2021
Last Updated
February 24, 2022
Results First Posted
February 24, 2022
Record last verified: 2022-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer 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 de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request 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 shared.