Merkel Cell Carcinoma, Small Cell Lung Cancer
Conditions
Keywords
MCC, SCLC
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.
Interventions
BIOLOGICALXmAb18087
Monoclonal bispecific antibody
DRUGXmAb18087 ± Pembrolizumab
XmAb18087 ± Pembrolizumab
Sponsors
ICON plc
Xencor, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | Day 1 (after dosing) up to end of study (up to 163 days) | 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. |
| 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
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Maximum Observed Serum Concentration | Predose up to end of study (up to 163 days) |
| Duration of Response | 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) |
| 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) |
Countries
United States
Participant flow
Recruitment details
The study has been terminated early by the sponsor. No participants with advanced Merkel Cell Carcinoma (MCC) not previously treated with anti-programmed cell death 1 (PD1) or anti-programmed cell death ligand 1 (PDL1) agents were enrolled for Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: XmAb18087 Monotherapy Participants with previously treated advanced MCC were administered XmAb18087 Monotherapy. | 2 |
| Part C: XmAb18087 Monotherapy Participants with previously treated extensive-stage SCLC were administered XmAb18087 monotherapy. | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Part C: XmAb18087 Monotherapy | Total | Part A: XmAb18087 Monotherapy |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | 0 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | 0 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | 0 Participants | — |
| Race (NIH/OMB) American Indian or Alaska Native | — | 0 Participants | — |
| Race (NIH/OMB) Asian | — | 0 Participants | — |
| Race (NIH/OMB) Black or African American | — | 0 Participants | — |
| Race (NIH/OMB) More than one race | — | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | — | 0 Participants | — |
| Race (NIH/OMB) White | — | 0 Participants | — |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 2 / 2 |
| other Total, other adverse events | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 | 2 / 2 |
Outcome results
Primary
Complete and Partial Response Rate as Assessed by RECIST 1.1 Criteria
Time frame: Up to end of study (up to 163 days)
Population: Data were not collected for the prespecified analysis of this outcome measure. No participants were enrolled for Part B.
Primary
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.
Time frame: Day 1 (after dosing) up to end of study (up to 163 days)
Population: All participants who received at least 1 dose of XmAb18087. No participants were enrolled for Part B, therefore, only Parts A and C results are reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: XmAb18087 Monotherapy | Number of Participants With Treatment-emergent Adverse Events | 2 Participants |
| Part C: XmAb18087 Monotherapy | Number of Participants With Treatment-emergent Adverse Events | 2 Participants |
Primary
Overall Response Rate as Assessed by RECIST 1.1 Criteria
Time frame: Up to end of study (up to 163 days)
Population: Data were not collected for the prespecified analysis of this outcome measure. No participants were enrolled for Part B.
Secondary
Duration of Response
Time frame: Up to end of study (up to 163 days)
Population: Data were not collected for the prespecified analysis of this outcome measure. No participants were enrolled for Part B.
Secondary
Immunogenicity: Number of Participants With Anti-XmAb18087 Antibodies
Time frame: Up to end of study (up to 163 days)
Population: Analysis was not performed as data were not collected for this outcome measure due to early study termination. No participants were enrolled for Part B.
Secondary
Overall Survival as Assessed by Per RECIST 1.1 Criteria
Time frame: Up to end of study (up to 163 days)
Population: Data was not collected for the prespecified analysis of this outcome measure. No participants were enrolled for Part B.
Secondary
Pharmacokinetics: Maximum Observed Serum Concentration
Time frame: Predose up to end of study (up to 163 days)
Population: Analysis was not performed as data were not collected for this outcome measure due to early study termination. No participants were enrolled for Part B.
Secondary
Progression-free Survival as Assessed by Per RECIST 1.1 Criteria
Time frame: Up to end of study (up to 163 days)
Population: Data were not collected for the prespecified analysis of this outcome measure. No participants were enrolled for Part B.