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

• ClinicalTrials.gov Identifier: NCT05996445
• Recruitment Status: Recruiting
• First Posted: August 18, 2023
• Last Update Posted: August 18, 2023
• Sponsor: Xencor, Inc.
• Information provided by (Responsible Party): Xencor, Inc.

Tracking Information

• First Submitted Date: June 23, 2023
• First Posted Date: August 18, 2023
• Last Update Posted Date: August 18, 2023
• Actual Study Start Date: July 28, 2023
• Estimated Primary Completion Date: September 30, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 10, 2023)

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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 10, 2023)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Sequential Assignments

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Solid Tumors

Intervention

• Biological: XmAb662
  Intravenous (IV) administration
• Biological: Keytruda® (pembrolizumab)
  Intravenous (IV) administration

Study Arms

• Experimental: Dose Escalation and Expansion XmAb662 administered as monotherapy
  Intervention: Biological: XmAb662
• Experimental: Dose Escalation and Expansion XmAb662 administered in combination with pembrolizumbab
  Interventions:

  • Biological: XmAb662
  • Biological: Keytruda® (pembrolizumab)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 10, 2023): 210
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2030
• Estimated Primary Completion Date: September 30, 2028 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Benjamin Thompson, MD, PhD; 619-517-7381; bthompson@xencor.com

Contact: Ines Hoffmann; 619- 994-8161; ihoffmann@xencor.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05996445
• Other Study ID Numbers: XmAb662-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Xencor, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Xencor, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Chet Bohac, MD; Executive Medical Director, Clinical Development

• PRS Account: Xencor, Inc.
• Verification Date: August 2023