Clinical trial NCT03794544: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Resectable
Early-stage
NSCLC
Keywords: Neoadjuvant
Non-small Cell Lung Cancer
Cancer
Lung
Resectable
Early-stage
Stage I
Stage II
Stage IIIA
Durvalumab
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2019-01-07
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 102
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Major Pathological Response Rate
timeFrame: Day 1 through Day 42
Secondary outcomes:
measure: Pathological Complete Response (pCR) Rate
timeFrame: Day 1 through Day 42
measure: Feasibility to Surgery
timeFrame: Day 29 to Day 42 after Week 1 Day 1
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From Day 1 through Day 105
measure: Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities
timeFrame: From Day 1 through Day 105
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: From Day 1 through Day 105
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Leesburg
country: United States
facility: Research Site
state: Florida
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Marseille Cedex 9
country: France
facility: Research Site
city: Toulouse CEDEX 09
country: France
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Zurich
country: Switzerland
facility: Research Site
Study officials:
References: