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

Nonsquamous Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06173505
• Other study ID #: XmAb717-06
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 27, 2023
• Est. completion date: October 2027

Study information

• Verified date: June 2024
• Source: Xencor, Inc.
• Contact: Michael Chiarella
• Phone: 1-858-945-2415
• Email: mchiarella[@]xencor.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: October 2027
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Nonsquamous Non-small Cell Lung Cancer

Intervention

Combination Product:
• Vudalimab + Carboplatin + Pemetrexed
Vudalimab intravenous + carboplatin intravenous + pemetrexed intravenous
• Pembrolizumab + Carboplatin + Pemetrexed
Pembrolizumab intravenous + carboplatin intravenous + pemetrexed intravenous

Locations

Country	Name	City	State
United States	New Jersey Center for Cancer Research	Brick	New Jersey
United States	Hematology Associates of Fredericksburg	Fredericksburg	Virginia
United States	Palo Verde Cancer Specialists	Glendale	Arizona
United States	Cancer and Blood Specialty Clinic	Los Alamitos	California
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Mid Florida Hematology and Oncology Center	Orange City	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Xencor, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Part 2: Progression free survival	Progressive disease per RECIST 1.1 or death, whichever comes first	Day 1 to 2.5 years
Secondary	Antitumor activity	Objective response rate as determined by investigator, duration of response (Part 1 and Part 2)	Day 1 to 1.4 years
Secondary	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
Secondary	Maximum Serum Drug Concentration (Cmax)	(Part 1 and Part 2)	Day 1 to 1.4 years
Secondary	Trough Serum Drug Concentration (Ctrough)	(Part 1 and Part 2)	Day 1 to 1.4 years
Secondary	Area Under the Concentration-time Curve (AUC)	(Part 1 and Part 2)	Day 1 to 1.4 years
Secondary	Overall survival	Time to death from any cause (Part 2)	Day 1 to 2.5 years
Secondary	Incidence of treatment-emergent adverse events		Time Frame: Day 1 to 1.4 years]