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

Primary Purpose

Resectable, Early-stage, NSCLC

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Durvalumab
Oleclumab
Monalizumab
Danvatirsen
Sponsored by
MedImmune LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Resectable focused on measuring Neoadjuvant, Non-small Cell Lung Cancer, Cancer, Lung, Resectable, Early-stage, Stage I, Stage II, Stage IIIA, Durvalumab

Eligibility Criteria

18 Years - 102 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
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  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Durvalumab 1500 mg

Durvalumab 1500 mg + Oleclumab 3000 mg

Durvalumab 1500 mg + Monalizumab 750 mg

Durvalumab 1500 mg + Danvatirsen 200 mg

Arm Description

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).

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).

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).

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).

Outcomes

Primary Outcome Measures

Major Pathological Response Rate
Major pathological response rate is defined as percentage of participants with <=10% residual viable tumor cells in the resected specimen.

Secondary Outcome Measures

Pathological Complete Response (pCR) Rate
The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen.
Feasibility to Surgery
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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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.
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities
Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis.
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Participants with abnormal vital sign reported as TEAEs are reported.

Full Information

First Posted
December 10, 2018
Last Updated
February 23, 2022
Sponsor
MedImmune LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03794544
Brief Title
Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Resectable Non-Small Cell Lung Cancer
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
March 8, 2019 (Actual)
Primary Completion Date
January 13, 2021 (Actual)
Study Completion Date
January 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC

4. Oversight

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

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Resectable, Early-stage, NSCLC
Keywords
Neoadjuvant, Non-small Cell Lung Cancer, Cancer, Lung, Resectable, Early-stage, Stage I, Stage II, Stage IIIA, Durvalumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Durvalumab 1500 mg
Arm Type
Experimental
Arm Description
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).
Arm Title
Durvalumab 1500 mg + Oleclumab 3000 mg
Arm Type
Experimental
Arm Description
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).
Arm Title
Durvalumab 1500 mg + Monalizumab 750 mg
Arm Type
Experimental
Arm Description
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).
Arm Title
Durvalumab 1500 mg + Danvatirsen 200 mg
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
MEDI4736
Intervention Description
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
Combination Product
Intervention Name(s)
Oleclumab
Other Intervention Name(s)
MEDI9447
Intervention Description
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
Intervention Name(s)
Monalizumab
Other Intervention Name(s)
IPH2201
Intervention Description
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
Intervention Name(s)
Danvatirsen
Other Intervention Name(s)
AZD9150
Intervention Description
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.
Primary Outcome Measure Information:
Title
Major Pathological Response Rate
Description
Major pathological response rate is defined as percentage of participants with <=10% residual viable tumor cells in the resected specimen.
Time Frame
Day 1 through Day 42
Secondary Outcome Measure Information:
Title
Pathological Complete Response (pCR) Rate
Description
The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen.
Time Frame
Day 1 through Day 42
Title
Feasibility to Surgery
Description
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.
Time Frame
Day 29 to Day 42 after Week 1 Day 1
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Description
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.
Time Frame
From Day 1 through Day 105
Title
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities
Description
Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis.
Time Frame
From Day 1 through Day 105
Title
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Description
Participants with abnormal vital sign reported as TEAEs are reported.
Time Frame
From Day 1 through Day 105

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
102 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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 Receipt of live attenuated vaccination within 30 days prior to study entry History of another primary malignancy except for: Curative-treated malignancy with no known active disease > 2 years before enrollment on the study Curative-treated non-melanoma skin cancer and/or carcinoma in-situ
Facility Information:
Facility Name
Research Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Research Site
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
Research Site
City
Leesburg
State/Province
Florida
ZIP/Postal Code
34748
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Research Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Research Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Research Site
City
Marseille Cedex 9
ZIP/Postal Code
13009
Country
France
Facility Name
Research Site
City
Toulouse CEDEX 09
ZIP/Postal Code
31059
Country
France
Facility Name
Research Site
City
Orbassano
ZIP/Postal Code
10043
Country
Italy
Facility Name
Research Site
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Research Site
City
A Coruña
ZIP/Postal Code
15001
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Research Site
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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
IPD Sharing 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
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D9108C00002&amp;attachmentIdentifier=e88d14fa-1bd3-4d48-b0e5-6834aadf8fef&amp;fileName=NeoCOAST_Protocol_Amd_2_redacted.pdf&amp;versionIdentifier=
Description
Related Info
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D9108C00002&amp;attachmentIdentifier=4040b9c0-98e9-4de7-ac0d-a934f8c86908&amp;fileName=d9108c00002-sap-ed4_redacted.pdf&amp;versionIdentifier=
Description
Related Info
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D9108C00002&amp;attachmentIdentifier=0eea76d6-523a-4327-a88e-863b0e6531e4&amp;fileName=Synopsis-NeoCOAST_Final_version_01Dec21-Redacted.pdf&amp;versionIdentifier=
Description
Related Info

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

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