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

Study Overview
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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).

Official Title
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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)

Conditions
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Resectable, Early-stage, NSCLC

Intervention / Treatment
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* Drug: Durvalumab
* Combination Product: Oleclumab
* Combination Product: Monalizumab
* Combination Product: Danvatirsen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 102 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Durvalumab 1500 mg<br>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<br>* 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.<br>* Other names: MEDI4736;|
| Experimental: Durvalumab 1500 mg + Oleclumab 3000 mg<br>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<br>* 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.<br>* Other names: MEDI4736;Combination Product: Oleclumab<br>* 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.<br>* Other names: MEDI9447;|
| Experimental: Durvalumab 1500 mg + Monalizumab 750 mg<br>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<br>* 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.<br>* Other names: MEDI4736;Combination Product: Monalizumab<br>* 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.<br>* Other names: IPH2201;|
| Experimental: Durvalumab 1500 mg + Danvatirsen 200 mg<br>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<br>* 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.<br>* Other names: MEDI4736;Combination Product: Danvatirsen<br>* 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.<br>* Other names: AZD9150;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR) Rate | The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen. | Day 1 through Day 42 | 
| 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. | Day 29 to Day 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. | From Day 1 through Day 105 | 
| 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. | From Day 1 through Day 105 | 
| Number of Participants With Abnormal Vital Signs Reported as TEAEs | Participants with abnormal vital sign reported as TEAEs are reported. | From Day 1 through Day 105 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant, Non-small Cell Lung Cancer, Cancer, Lung, Resectable, Early-stage, Stage I, Stage II, Stage IIIA, Durvalumab