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

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

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).

Study Overview

• Status: Terminated
• Conditions: Nonsquamous Non-small Cell Lung Cancer
• Intervention / Treatment: Combination product: Vudalimab + Carboplatin + Pemetrexed; Combination product: Pembrolizumab + Carboplatin + Pemetrexed

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis - Campus Virga Jesse
• Greece
  • Thessaloniki, Greece, 552 36
    • St. Lukes (Agios Loucas) Hospital
• Malaysia
  • Johor Bahru, Malaysia, 81100
    • Hospital Sultan Ismail
  • Kuching, Malaysia, 93586
    • Hospital Umum Sarawak
  • Putrajaya, Malaysia, 62250
    • Institut Kanser Negara
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1066 CX
      • The Netherlands Cancer Institute - Antoni van Leeuwenhoek
• Portugal
  • Guimarães, Portugal, 4835-044
    • ULS do Alto Ave, EPE - Hospital da Senhora da Oliveira Guimarães
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08023
    • Next Oncology-Hospital Quironsalud Barcelona
  • Girona, Spain, 17007
    • Institut Català d'Oncolgia de Girona
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
• United States
  • Arizona
    • Glendale, Arizona, United States, 85304
      • Palo Verde Cancer Specialists
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology Associates
  • Virginia
    • Fredericksburg, Virginia, United States, 22408
      • Hematology Associates of Fredericksburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vudalimab + Carboplatin + Pemetrexed	Combination product: Vudalimab + Carboplatin + Pemetrexed; Vudalimab intravenous + carboplatin intravenous + pemetrexed intravenous
Active Comparator: Pembrolizumab + Carboplatin + Pemetrexed	Combination product: Pembrolizumab + Carboplatin + Pemetrexed; Pembrolizumab intravenous + carboplatin intravenous + pemetrexed intravenous

What is the study measuring?

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]

Collaborators and Investigators

• Sponsor: Xencor, Inc.
• Investigators: Study Director: Jolene Shorr, Executive Director, Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2023
• Primary Completion (Actual): December 24, 2025
• Study Completion (Actual): December 29, 2025

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: chemotherapy; Non-small cell lung cancer; checkpoint inhibitor; Nonsquamous; vudalimab; XmAb20717; anti-PD-1 x anti-CTLA-4
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Pemetrexed; Carboplatin; pembrolizumab
• Other Study ID Numbers: XmAb717-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No