Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
MedImmune LLC

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

Layout table for study information
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Durvalumab

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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03794544


Locations
Layout table for location information
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

Additional Information:
Layout table for additonal information
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03794544    
Other Study ID Numbers: D9108C00002
First Posted: January 7, 2019    Key Record Dates
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

Layout table for additional information
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:
Layout table for 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