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

• ClinicalTrials.gov Identifier: NCT03794544
• Recruitment Status: Completed
• First Posted: January 7, 2019
• Results First Posted: February 24, 2022
• Last Update Posted: February 24, 2022
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Resectable; Early-stage; NSCLC	Drug: Durvalumab; Combination Product: Oleclumab; Combination Product: Monalizumab; Combination Product: Danvatirsen	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: March 8, 2019
• Actual Primary Completion Date: January 13, 2021
• Actual Study Completion Date: January 13, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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).	Drug: 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.; Other Name: MEDI4736
Experimental: 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).	Drug: 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.; Other Name: MEDI4736; Combination Product: 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.; Other Name: MEDI9447
Experimental: 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).	Drug: 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.; Other Name: MEDI4736; 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.; Other Name: IPH2201
Experimental: 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).	Drug: 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.; Other Name: MEDI4736; 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.; Other Name: AZD9150

Outcome Measures

Primary Outcome Measures :

1. Major Pathological Response Rate [ Time Frame: Day 1 through Day 42 ]
   Major pathological response rate is defined as percentage of participants with <=10% residual viable tumor cells in the resected specimen.

Secondary Outcome Measures :

1. Pathological Complete Response (pCR) Rate [ Time Frame: Day 1 through Day 42 ]
   The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen.
2. Feasibility to Surgery [ Time Frame: Day 29 to Day 42 after Week 1 Day 1 ]
   Feasibility to surgery is defined as the percentage of participants who underwent the planned surgery within Days 29 to 42 after Week 1 Day 1.
3. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [ Time Frame: From Day 1 through Day 105 ]
   An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
4. Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities [ Time Frame: From Day 1 through Day 105 ]
   Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis.
5. Number of Participants With Abnormal Vital Signs Reported as TEAEs [ Time Frame: From Day 1 through Day 105 ]
   Participants with abnormal vital sign reported as TEAEs are reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 102 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Research Site

La Jolla, California, United States, 92093

United States, Florida

Research Site

Fort Myers, Florida, United States, 33901

Research Site

Leesburg, Florida, United States, 34748

United States, Maryland

Research Site

Baltimore, Maryland, United States, 21231

United States, New York

Research Site

Buffalo, New York, United States, 14263

Research Site

New York, New York, United States, 10016

United States, Tennessee

Research Site

Chattanooga, Tennessee, United States, 37404

Research Site

Nashville, Tennessee, United States, 37203

United States, Texas

Research Site

Houston, Texas, United States, 77030

United States, Virginia

Research Site

Fairfax, Virginia, United States, 22031

Canada, Quebec

Research Site

Montreal, Quebec, Canada, H4A 3J1

France

Research Site

Marseille Cedex 9, France, 13009

Research Site

Toulouse CEDEX 09, France, 31059

Italy

Research Site

Orbassano, Italy, 10043

Portugal

Research Site

Porto, Portugal, 4200-072

Spain

Research Site

A Coruña, Spain, 15001

Research Site

Barcelona, Spain, 08916

Switzerland

Research Site

Zurich, Switzerland, 8091

Sponsors and Collaborators

MedImmune LLC

  Study Documents (Full-Text)

Documents provided by MedImmune LLC:

Study Protocol  [PDF] January 18, 2019

Statistical Analysis Plan  [PDF] August 10, 2021

More Information

Additional Information:

Related Info 

Related Info 

Related Info 

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT03794544
• Other Study ID Numbers: D9108C00002
• First Posted: January 7, 2019
• Results First Posted: February 24, 2022
• Last Update Posted: February 24, 2022
• Last Verified: February 2022

Individual Participant Data (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. 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.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (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
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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

Keywords provided by MedImmune LLC:

Neoadjuvant; Non-small Cell Lung Cancer; Cancer; Lung; Resectable; Early-stage; Stage I; Stage II; Stage IIIA; Durvalumab

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Durvalumab; Antineoplastic Agents, Immunological; Antineoplastic Agents