Safety and Efficacy of XmAb18087 ± Pembrolizumab in Advanced Merkel Cell Carcinoma or Extensive-stage Small Cell Lung Cancer

NCT04590781 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: XmAb18087-02DUET 1-02
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 7

Brief Summary

This is a Phase 1b/2, multiple-dose study designed to describe safety and efficacy, and to assess PK and immunogenicity of XmAb18087 monotherapy and in combination with pembrolizumab in participants with metastatic Merkel cell (MCC) or locoregional MCC that has recurred after locoregional therapy with surgery and/or radiation therapy, and mAb18087 monotherapy in participants with extensive-stage small cell lung cancer (SCLC) that has progressed after standard therapies. This study was terminated by the sponsor. No participants enrolled in Part B.

Conditions

Merkel Cell Carcinoma; Small Cell Lung Cancer

Keywords

MCC; SCLC

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment-emergent Adverse Events

  A treatment-emergent adverse event (TEAE) was any untoward medical occurrence in a participant treated with study drug. The TEAE does not necessarily have a causal relationship with this treatment. A TEAE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. TEAEs may include the onset of new illness and the exacerbation of preexisting conditions. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section."

  Day 1 (after dosing) up to end of study (up to 163 days)

• Overall Response Rate as Assessed by RECIST 1.1 Criteria

  Up to end of study (up to 163 days)

• Complete and Partial Response Rate as Assessed by RECIST 1.1 Criteria

  Up to end of study (up to 163 days)

Secondary Outcomes (5)

• Duration of Response

  Up to end of study (up to 163 days)

• Progression-free Survival as Assessed by Per RECIST 1.1 Criteria

  Up to end of study (up to 163 days)

• Overall Survival as Assessed by Per RECIST 1.1 Criteria

  Up to end of study (up to 163 days)

• Pharmacokinetics: Maximum Observed Serum Concentration

  Predose up to end of study (up to 163 days)

• Immunogenicity: Number of Participants With Anti-XmAb18087 Antibodies

  Up to end of study (up to 163 days)

Study Arms (3)

Part A: XmAb18087 Monotherapy

EXPERIMENTAL

Part A, will enroll participants with previously treated advanced MCC, consists of safety-run in cohorts followed by an expansion cohort.

Biological: XmAb18087

Part B: XmAb18087 + pembrolizumab

EXPERIMENTAL

Part B, will enroll participants with advanced MCC not previously treated with anti-programmed cell death 1 (PD1) or anti-programmed cell death ligand 1 (PDL1) agents, consists of safety run-in cohorts followed by an expansion cohort.

Drug: XmAb18087 ± Pembrolizumab

Part C: XmAb18087 monotherapy

EXPERIMENTAL

Part C will enroll participants with previously treated extensive-stage SCLC and consists of safety-run in cohorts followed by an expansion cohort.

Biological: XmAb18087

Interventions

XmAb18087 BIOLOGICAL

Monoclonal bispecific antibody

Part A: XmAb18087 Monotherapy; Part C: XmAb18087 monotherapy

XmAb18087 ± Pembrolizumab DRUG

XmAb18087 ± Pembrolizumab

Part B: XmAb18087 + pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent
• Adult participants ≥ 18 years
• Disease measurable by RECIST 1.1 criteria using either computed tomography (CT) or magnetic resonance imaging (MRI) scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• All participants must have adequate archival tumor sample (slides or archival formalin-fixed paraffin-embedded \[FFPE\] block\[s\] containing tumor that has not been previously irradiated
• Female participants of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after completion of study. success), or sexual abstinence
• Fertile male participants must be willing to practice a highly effective method of birth control for the duration of the study and continuing for 4 weeks after the last dose of XmAb18087 or pembrolizumab (when applicable
• Able and willing to complete the entire study according to the study schedule
• Histologically or cytologically confirmed metastatic MCC or locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy.
• Participants must have progressed on or been ineligible for treatment with anti-PD1 or anti-PDL1 therapy.
• Participants must be eligible to receive pembrolizumab as standard of care.
• Histologically or cytologically confirmed extensive-stage SCLC that has progressed following standard therapies

You may not qualify if:

• Prior treatment with therapeutics directed at anti-programmed cell death 1 (anti-PD1) or anti-programmed cell death ligand 1 (anti-PDL1)
• Have severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients

Sponsors & Collaborators

• Xencor, Inc.: lead
• ICON plc: collaborator

Study Sites (7)

City of Hope

Duarte, California, 91010, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

OU Health, Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98109, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Study was terminated by the sponsor and only 2 participants each were enrolled in Parts A and C. No participants were enrolled for Part B. Data were not collected for the prespecified analyses of efficacy, pharmacokinetics, and immunogenicity outcome measures.

Results Point of Contact

• Title: Benjamin Thompson, MD, PhD
• Organization: Xencor, Inc

bthompson@xencor.com

858-480-3133

Study Officials

• Benjamin Thompson, MD, PhD

  Medical Director, Clinical Development, Xencor

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: October 19, 2020
• Study Start: May 10, 2021
• Primary Completion: March 24, 2022
• Study Completion: March 24, 2022
• Last Updated: April 20, 2023
• Results First Posted: April 20, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)