Nonsquamous Non-small Cell Lung Cancer
Conditions
Keywords
Non-small cell lung cancer, Nonsquamous, XmAb20717, vudalimab, anti-PD-1 x anti-CTLA-4, checkpoint inhibitor, chemotherapy
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.
Interventions
COMBINATION_PRODUCTVudalimab + Carboplatin + Pemetrexed
Vudalimab intravenous + carboplatin intravenous + pemetrexed intravenous
COMBINATION_PRODUCTPembrolizumab + Carboplatin + Pemetrexed
Pembrolizumab intravenous + carboplatin intravenous + pemetrexed intravenous
Sponsors
Xencor, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Antitumor activity | Day 1 to 1.4 years | Objective response rate as determined by investigator, duration of response (Part 1 and Part 2) |
| 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) |
| Maximum Serum Drug Concentration (Cmax) | Day 1 to 1.4 years | (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) |
| 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] | — |
Countries
Belgium, Greece, Malaysia, Netherlands, Portugal, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORJolene Shorr
Executive Director, Clinical Development
Outcome results
None listed