A Study of XmAb®662 as Monotherapy or in Combination With Pembrolizumab in Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Biological: XmAb662
* Biological: Keytruda® (pembrolizumab)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential Assignments
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation and Expansion XmAb662 administered as monotherapy<br> | Biological: XmAb662<br>* Intravenous (IV) administration<br>|
| Experimental: Dose Escalation and Expansion XmAb662 administered in combination with pembrolizumbab<br> | Biological: XmAb662<br>* Intravenous (IV) administration<br>Biological: Keytruda® (pembrolizumab)<br>* Intravenous (IV) administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities (DLTs) | Safety and tolerability as assessed by incidence of DLTs and all available data which will be used to determine the recommend dose(s) | First 3 weeks on treatment for each subject] | 
| Incidence and severity of treatment emergent adverse events (TEAEs) | Safety and tolerability as assessed by incidence of TEAEs, including clinically significant changes in safety laboratory tests and clinical findings | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of pharmacokinetics | Measurement of Cmax | 56 Days | 
| Characterization of pharmacokinetics | Measurement of AUC | 56 Days | 
| Objective response rate | Objective response rate by RECIST 1.1, as modified by PCWG3 for participants with prostate cancer | Up to 2 years | 
| Progression-free survival | Progression-free survival by RECIST 1.1, as modified by PCWG3 for participants with prostate cancer | Up to 2 years | 
| Duration of response | Duration of response by RECIST 1.1, as modified by PCWG3 for participants with prostate cancer | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IL-12,, interleukin-12, pembrolizumab, Advanced Solid Tumors, Metastatic Solid Tumors