Study of Vudalimab or Pembrolizumab in Combination With Chemotherapy as First-line Treatment in Patients With Advanced NSCLC
- Conditions
- Nonsquamous Non-small Cell Lung Cancer
- Interventions
- Combination Product: Pembrolizumab + Carboplatin + PemetrexedCombination Product: Vudalimab + Carboplatin + Pemetrexed
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 168
- 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
- 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
- Arm && Interventions
Group Intervention Description Pembrolizumab + Carboplatin + Pemetrexed Pembrolizumab + Carboplatin + Pemetrexed - Vudalimab + Carboplatin + Pemetrexed Vudalimab + Carboplatin + Pemetrexed -
- Primary Outcome Measures
Name Time Method 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
Part 2: Progression free survival Day 1 to 2.5 years Progressive disease per RECIST 1.1 or death, whichever comes first
- 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
START MADRID-Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Y Politécnico La Fe
🇪🇸Valencia, Spain
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan City, Taiwan
Palo Verde Cancer Specialists
🇺🇸Glendale, Arizona, United States
Western Regional Medical Center
🇺🇸Goodyear, Arizona, United States
Cancer and Blood Specialty Clinic
🇺🇸Los Alamitos, California, United States
Eastern Connecticut Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
Mid Florida Hematology and Oncology Center
🇺🇸Orange City, Florida, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Maple Grove, Minnesota, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
New Jersey Center for Cancer Research
🇺🇸Brick, New Jersey, United States
Cancer Institute at Phelps
🇺🇸Sleepy Hollow, New York, United States
Consultants in Medical Oncology and Hematology, P.C.
🇺🇸Broomall, Pennsylvania, United States
Alliance Cancer Specialists
🇺🇸Horsham, Pennsylvania, United States
Hematology Associates of Fredericksburg
🇺🇸Fredericksburg, Virginia, United States
Jessa Ziekenhuis - Campus Virga Jesse
🇧🇪Hasselt, Belgium
Hospital Canselor Tuanku Muhriz
🇲🇾Cheras, Malaysia
Hospital Sultan Ismail
🇲🇾Johor Bahru, Malaysia
Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
Institut Kanser Negara
🇲🇾Putrajaya, Malaysia
Columbia Asia Hospital Bukit Rimau
🇲🇾Shah Alam, Malaysia
The Netherlands Cancer Institute - Antoni van Leeuwenhoek
🇳🇱Amsterdam, North Holland, Netherlands
NEXT Oncology-Hospital Quirónsalud Barcelona
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Institut Català d'Oncolgia de Girona
🇪🇸Girona, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
NEXT Oncology-Hospital Quirónsalud Madrid
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan