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

Phase 1

Recruiting

• Conditions: Nonsquamous Non-small Cell Lung Cancer

• Registration Number: NCT06173505
• Lead Sponsor: Xencor, Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-11-13
• Study First Submitted QC: 2023-12-07
• Study First Posted: 2023-12-15
• Study Start: 2023-12-27
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-02
• Last Update Posted: 2024-12-04
• Primary Completion: 2026-10
• Study Completion: 2027-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 168

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (43)

Memorial Cancer Institute at Memorial Hospital West; 🇺🇸 Pembroke Pines, Florida, United States

Midwestern Regional Medical Center; 🇺🇸 Zion, Illinois, United States

Athens Medical Center; 🇬🇷 Athens, Greece

St. Lukes (Agios Loucas) Hospital; 🇬🇷 Thessaloníki, Greece

Pantai Hospital Ipoh; 🇲🇾 Ipoh, Malaysia

Med-Polonia Sp. Z o.o.; 🇵🇱 Poznań, Poland

ULS do Alto Ave, EPE - Hospital da Senhora da Oliveira Guimarães; 🇵🇹 Guimarães, Portugal

Hospital Santo António dos Capuchos - Unidade Local de Saúde de São José; 🇵🇹 Lisboa, Portugal

Instituto Português de Oncologia de Porto Francisco Gentil, E.P.E.; 🇵🇹 Porto, Portugal

Hospital Universitario Vall d'Hebrón; 🇪🇸 Barcelona, Spain

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