Clinical trial NCT05996445: A Study of XmAb®662 as Monotherapy or in Combination With Pembrolizumab in Advanced Solid Tumors
Official title: A Phase 1, First-in-Human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of XmAb®662 in Monotherapy or in Combination With Pembrolizumab in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: IL-12,
interleukin-12
pembrolizumab
Advanced Solid Tumors
Metastatic Solid Tumors
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-18
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Sequential Assignments
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous administration of XmAb662 monotherapy or in combination with pembrolizumab in subjects with advanced solid tumors and to identify the recommended dose regimen that is safe and biologically effective for XmAb662.

Detailed description: This is a first-in-human (FIH), Phase 1, open-label, multicenter dose escalation study with cohort expansion at one or more recommended dose(s) (RDs), designed to evaluate the safety and tolerability of XmAb662 monotherapy or in combination with pembrolizumab in subjects with selected solid tumors that have progressed after standard/approved therapies, or for which there are no effective available therapies. This study will be conducted in 2 parts: dose escalation (Part 1) and dose expansion (Part 2), and subdivided into arms for XmAb662 monotherapy and XmAb662+pembrolizumab combination.

Eligibility criteria: Inclusion Criteria:

Advanced, recurrent or metastatic solid malignancy that is not amenable to curative-intent treatment and which has progressed after standard therapy appropriate for the following tumor type: Head and neck squamous cell carcinoma, melanoma, non-small cell lung cancer, small cell lung cancer (SCLC), urothelial carcinoma, colorectal cancer, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, endometrial cancer, cutaneous squamous cell carcinoma, breast cancer, ovarian cancer (epithelial), castration-resistant prostate cancer (adenocarcinoma)

Measurable disease by RECIST 1.1; subjects with prostate cancer who have evaluable disease according to PCWG3 criteria may enroll

Life expectancy of at least 3 months

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

For dose escalation cohorts, subjects must have adequate archival tumor sample or willing to provide a fresh tumor

Adequate organ function

Exclusion Criteria:

Receiving treatment with the following therapies: Interleukin (IL)-12 either alone or as part of a treatment regimen; checkpoint inhibitors given within 4 weeks of study drug; other anticancer therapies, including chemotherapy or radiation therapy, given within 4 weeks of the start of study drug (palliative radiation given within a 1-week washout is allowed)

History of allergic or anaphylactic/hypersensitivity reaction to immunotherapy

History of a life-threatening (Grade 4) immune-related adverse event (irAE) related to prior immunotherapy or any prior irAE, regardless of grade

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 their primary malignancy

Known active central nervous system involvement by malignant disease; subjects with previously treated brain metastases may participate provided they are radiologically and clinically stable

For subjects receiving pembrolizumab, prior Grade 3 or Grade 4 infusion-related reactions to pembrolizumab, or known hypersensitivity to pembrolizumab

Other protocol defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: First 3 weeks on treatment for each subject]
measure: Incidence and severity of treatment emergent adverse events (TEAEs)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Characterization of pharmacokinetics
timeFrame: 56 Days
measure: Characterization of pharmacokinetics
timeFrame: 56 Days
measure: Objective response rate
timeFrame: Up to 2 years
measure: Progression-free survival
timeFrame: Up to 2 years
measure: Duration of response
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Charlottesville
country: United States
facility: University Of Virginia Comprehensive Cancer Center
state: Virginia
Study officials:
affiliation: Executive Medical Director, Clinical Development
name: Chet Bohac, MD
role: STUDY_DIRECTOR
References: