Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Resectable Non-Small Cell Lung Cancer

NCT ID: NCT03794544

Last Updated: 2022-02-24

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-08

Study Completion Date

2021-01-13

Brief Summary

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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).

Detailed Description

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Conditions

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Resectable Early-stage NSCLC

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be enrolled and randomized into a durvalumab monotherapy arm or into a durvalumab plus other novel therapy arms. Up to approximately 25 sites globally will participate in this study. New treatment arms may be added in the future. Participants will be treated with a single durvalumab dose alone or in combination with other agents. After the single cycle treatment period participants will have the standard surgical resection planned. All participants will have a post-resection monitoring visit. Study treatment will be discontinued upon disease progression, unacceptable toxicity, or other investigators' reasons.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Durvalumab 1500 mg

Participants 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).

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

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.

Durvalumab 1500 mg + Oleclumab 3000 mg

Participants 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).

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

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

Intervention Type COMBINATION_PRODUCT

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.

Durvalumab 1500 mg + Monalizumab 750 mg

Participants 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).

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

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.

Monalizumab

Intervention Type COMBINATION_PRODUCT

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.

Durvalumab 1500 mg + Danvatirsen 200 mg

Participants 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).

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

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.

Danvatirsen

Intervention Type COMBINATION_PRODUCT

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.

Interventions

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Durvalumab

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.

Intervention Type DRUG

Oleclumab

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.

Intervention Type COMBINATION_PRODUCT

Monalizumab

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.

Intervention Type COMBINATION_PRODUCT

Danvatirsen

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.

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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MEDI4736 MEDI9447 IPH2201 AZD9150

Eligibility Criteria

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Inclusion Criteria

1. Cytologically and/or histologically-documented NSCLC

1. 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
2. Amenable to complete surgical resection
3. Have not received any other therapy for this condition
2. Predicted forced expiratory volume in one second (FEV1) ≥ 50%
3. Predicted diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50%
4. ECOG 0 or 1
5. Adequate organ function

Exclusion Criteria

1. Participants with small-cell lung cancer or mixed small-cell lung cancer
2. Participants who require or may require pneumonectomy
3. Prior treatment with programmed cell death ligand-1 (PD-L1), PD-L1, or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors
4. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug.
5. Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion:

1. Participants with vitiligo or alopecia
2. Participants with hypothyroidism on hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Participants without active disease in the last 5 years may be included but only after consultation with the study physician
5. Participants with celiac disease controlled by diet alone
6. Pregnant or breast-feeding female
7. Major surgical procedure within prior 30 days
8. History of active primary immunodeficiency
9. Active infection including tuberculosis, hepatitis B, hepatitis C, or HIV
10. QTc interval (QTc) ≥ 470 ms
11. Uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent
12. Receipt of live attenuated vaccination within 30 days prior to study entry
13. History of another primary malignancy except for:

1. Curative-treated malignancy with no known active disease \> 2 years before enrollment on the study
2. Curative-treated non-melanoma skin cancer and/or carcinoma in-situ
Minimum Eligible Age

18 Years

Maximum Eligible Age

102 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

La Jolla, California, United States

Site Status

Research Site

Fort Myers, Florida, United States

Site Status

Research Site

Leesburg, Florida, United States

Site Status

Research Site

Baltimore, Maryland, United States

Site Status

Research Site

Buffalo, New York, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

Chattanooga, Tennessee, United States

Site Status

Research Site

Nashville, Tennessee, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Fairfax, Virginia, United States

Site Status

Research Site

Montreal, Quebec, Canada

Site Status

Research Site

Marseille, , France

Site Status

Research Site

Toulouse, , France

Site Status

Research Site

Orbassano, , Italy

Site Status

Research Site

Porto, , Portugal

Site Status

Research Site

A Coruña, , Spain

Site Status

Research Site

Barcelona, , Spain

Site Status

Research Site

Zurich, , Switzerland

Site Status

Countries

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United States Canada France Italy Portugal Spain Switzerland

References

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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.

Reference Type DERIVED
PMID: 37707791 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D9108C00002

Identifier Type: -

Identifier Source: org_study_id

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