Clinical trial NCT06173505: Study of Vudalimab or Pembrolizumab in Combination With Chemotherapy as First-line Treatment in Patients With Advanced NSCLC
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Nonsquamous Non-small Cell Lung Cancer
Keywords: Non-small cell lung cancer
Nonsquamous
XmAb20717
vudalimab
anti-PD-1 x anti-CTLA-4
checkpoint inhibitor
chemotherapy
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-15
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Recommended Phase 2 dose of vudalimab in combination with chemotherapy
timeFrame: Day 1 to Day 21
measure: Part 2: Progression free survival
timeFrame: Day 1 to 2.5 years
Secondary outcomes:
measure: Antitumor activity
timeFrame: Day 1 to 1.4 years
measure: Changes in circulating tumor DNA (ctDNA)
timeFrame: Day 1 to 1.4 years
measure: Maximum Serum Drug Concentration (Cmax)
timeFrame: Day 1 to 1.4 years
measure: Trough Serum Drug Concentration (Ctrough)
timeFrame: Day 1 to 1.4 years
measure: Area Under the Concentration-time Curve (AUC)
timeFrame: Day 1 to 1.4 years
measure: Overall survival
timeFrame: Day 1 to 2.5 years
measure: Incidence of treatment-emergent adverse events
timeFrame: Time Frame: Day 1 to 1.4 years]
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Palo Verde Cancer Specialists
state: Arizona
city: Goodyear
country: United States
facility: Western Regional Medical Center
state: Arizona
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute at Memorial Hospital West
state: Florida
city: Zion
country: United States
facility: Midwestern Regional Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Maple Grove
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Brick
country: United States
facility: New Jersey Center for Cancer Research
state: New Jersey
city: Sleepy Hollow
country: United States
facility: Cancer Institute at Phelps
state: New York
city: Broomall
country: United States
facility: Consultants in Medical Oncology and Hematology, P.C.
state: Pennsylvania
city: Horsham
country: United States
facility: Alliance Cancer Specialists
state: Pennsylvania
city: Fredericksburg
country: United States
facility: Hematology Associates of Fredericksburg
state: Virginia
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
city: Athens
country: Greece
facility: Athens Medical Center
city: Thessaloníki
country: Greece
facility: St. Lukes (Agios Loucas) Hospital
city: Cheras
country: Malaysia
facility: Hospital Canselor Tuanku Muhriz
city: Ipoh
country: Malaysia
facility: Pantai Hospital Ipoh
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Putrajaya
country: Malaysia
facility: Institut Kanser Negara
city: Shah Alam
country: Malaysia
facility: Columbia Asia Hospital Bukit Rimau
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute - Antoni van Leeuwenhoek
state: North Holland
city: Poznań
country: Poland
facility: Med-Polonia Sp. Z o.o.
city: Guimarães
country: Portugal
facility: ULS do Alto Ave, EPE - Hospital da Senhora da Oliveira Guimarães
city: Lisboa
country: Portugal
facility: Hospital Santo António dos Capuchos - Unidade Local de Saúde de São José
city: Porto
country: Portugal
facility: Instituto Português de Oncologia de Porto Francisco Gentil, E.P.E.
city: Barcelona
country: Spain
facility: NEXT Oncology-Hospital Quirónsalud Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Girona
country: Spain
facility: Institut Català d'Oncolgia de Girona
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: START MADRID-Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: NEXT Oncology-Hospital Quirónsalud Madrid
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario Y Politécnico La Fe
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
affiliation: Executive Director, Clinical Development
name: Jolene Shorr
role: STUDY_DIRECTOR
References: