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

Study Overview
=================
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.

Official Title
-----------------
A Phase 1b/2 Multiple-Dose Study to Evaluate the Safety and Efficacy of XmAb18087 ± Pembrolizumab in Subjects With Advanced Merkel Cell Carcinoma or Extensive-stage Small Cell Lung Cancer (DUET-1-02) Protocol

Conditions
-----------------
Merkel Cell Carcinoma, Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Biological: XmAb18087
* Drug: XmAb18087 ± Pembrolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Additional Inclusion Criteria for Part A and Part B Cohorts: • Histologically or cytologically confirmed metastatic MCC or locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy. Additional Inclusion Criteria for Part A Cohorts: • Participants must have progressed on or been ineligible for treatment with anti-PD1 or anti-PDL1 therapy. Additional Inclusion Criteria for Part B Cohorts: • Participants must be eligible to receive pembrolizumab as standard of care. Additional Inclusion Criteria for Part C Cohorts: • Histologically or cytologically confirmed extensive-stage SCLC that has progressed following standard therapies Exclusion Criteria: Additional Exclusion Criteria for Part B Cohorts: XmAb18087 in Combination with Pembrolizumab 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: XmAb18087 Monotherapy<br>Part A, will enroll participants with previously treated advanced MCC, consists of safety-run in cohorts followed by an expansion cohort. | Biological: XmAb18087<br>* Monoclonal bispecific antibody<br>|
| Experimental: Part B: XmAb18087 + pembrolizumab<br>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<br>* XmAb18087 ± Pembrolizumab<br>|
| Experimental: Part C: XmAb18087 monotherapy<br>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<br>* Monoclonal bispecific antibody<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MCC, SCLC