Study of Vudalimab or Pembrolizumab in Combination With Chemotherapy as First-line Treatment in Patients With Advanced NSCLC

Study Overview
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Brief Summary
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The purpose of this study is to identify the recommended dose of vudalimab to be used in combination with chemotherapy (Part 1) and to evaluate the efficacy and safety of vudalimab plus standard of care chemotherapy relative to pembrolizumab plus chemotherapy (Part 2) as first-line treatment in patients with nonsquamous non-small cell lung cancer (NSCLC).

Detailed Description
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This is a Phase 1b/2 study, multicenter, open-label, randomized study in patients with nonsquamous non-small cell lung cancer without prior treatment for metastatic disease. Part 1 is designed to identify the recommended Phase 2 dose (RP2D) of vudalimab, an anti-PD-1/CTLA-4 bispecific antibody, in combination with standard of care (SOC) chemotherapy. Part 2 will evaluate the efficacy and safety vudalimab, at the RP2D, plus SOC relative to pembrolizumab (anti-PD-1) plus SOC chemotherapy.

Official Title
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A Phase 1b/2, Open-label, Randomized Study of Vudalimab in Combination With Chemotherapy or Pembrolizumab in Combination With Chemotherapy as First-line Treatment in Patients With Advanced Non-small Cell Lung Cancer

Conditions
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Nonsquamous Non-small Cell Lung Cancer

Intervention / Treatment
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* Combination Product: Vudalimab + Carboplatin + Pemetrexed
* Combination Product: Pembrolizumab + Carboplatin + Pemetrexed


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed, locally advanced (unresectable) or metastatic nonsquamous NSCLC Documented absence of tumor activating EGFR mutation, ALK gene and ROS1 rearrangements, and alterations in any actionable driver oncogenes for which there are locally approved targeted first-line therapies PD-L1 IHC testing documenting TPS < 49% No prior systemic treatment for advanced/metastatic NSCLC. Measurable disease by RECIST 1.1 ECOG performance status score of 0 or 1 Life expectancy ≥ 3 months Adequate liver, kidney, thyroid and bone marrow function Key Exclusion Criteria: Have known active central nervous system metastases and/or carcinomatous meningitis. Patients with treated brain metastases may participate, provided they are radiologically stable Active known or suspected autoimmune disease Has any condition requiring systemic treatment with corticosteroids, prednisone equivalents, or other immunosuppressive medications within 14 days prior to first dose of study drug Interstitial lung disease that is symptomatic Known human immunodeficiency virus (HIV) positive with CD4+ T-cell (CD4+) count < 350 cells/μL, or an HIV viral load greater than 400 copies/mL, or a history of an acquired immunodeficiency syndrome-defining opportunistic infection within the past 12 months, or not on established antiretroviral therapy (ART) for at least 4 weeks prior to initiation of study drug dosing. (HIV positive subjects who do not meet these exclusion criteria are eligible) Positive test for hepatitis C RNA (a patient who is hepatitis C virus [HCV] antibody positive but HCV RNA negative due to documented, curative prior antiviral treatment or natural resolution is eligible) Positive test for hepatitis B surface antigen or hepatitis B core antibody (hBcAb) (a patient whose hBsAg is negative and hBcAb is positive may be enrolled if a hepatitis B virus (HBV) DNA test is negative and the subject is retested for HbsAg and HBV DNA every 2 months) History or evidence of any clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) other than NSCLC, that, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study evaluations, procedures, or completion Other protocol defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vudalimab + Carboplatin + Pemetrexed<br> | Combination Product: Vudalimab + Carboplatin + Pemetrexed<br>* Vudalimab intravenous + carboplatin intravenous + pemetrexed intravenous<br>|
| Active Comparator: Pembrolizumab + Carboplatin + Pemetrexed<br> | Combination Product: Pembrolizumab + Carboplatin + Pemetrexed<br>* Pembrolizumab intravenous + carboplatin intravenous + pemetrexed intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Recommended Phase 2 dose of vudalimab in combination with chemotherapy | Incidence of treatment-emergent adverse events and treatment-related adverse events leading to discontinuation of treatment | Day 1 to Day 21 | 
| Part 2: Progression free survival | Progressive disease per RECIST 1.1 or death, whichever comes first | Day 1 to 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor activity | Objective response rate as determined by investigator, duration of response (Part 1 and Part 2) | Day 1 to 1.4 years | 
| Changes in circulating tumor DNA (ctDNA) | Examine ctDNA changes as a surrogate marker for disease burden (Part 1 and Part 2) | Day 1 to 1.4 years | 
| Maximum Serum Drug Concentration (Cmax) | (Part 1 and Part 2) | Day 1 to 1.4 years | 
| Trough Serum Drug Concentration (Ctrough) | (Part 1 and Part 2) | Day 1 to 1.4 years | 
| Area Under the Concentration-time Curve (AUC) | (Part 1 and Part 2) | Day 1 to 1.4 years | 
| Overall survival | Time to death from any cause (Part 2) | Day 1 to 2.5 years | 
| Incidence of treatment-emergent adverse events |  | Time Frame: Day 1 to 1.4 years] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer, Nonsquamous, XmAb20717, vudalimab, anti-PD-1 x anti-CTLA-4, checkpoint inhibitor, chemotherapy