Advanced Melanoma
Conditions
Keywords
Neoplasms, Ipilimumab, Antineoplastic Agents, Immunological
Brief summary
This clinical trial is a Phase 2, open-label study to determine the anti-tumor activity of FLX475 in combination with ipilimumab in subjects with advanced melanoma previously treated with an anti-programmed cell death 1 (anti-PD-1) or anti-programmed cell death ligand 1 (anti-PD-L1) agent. The study will be conducted starting with a safety run-in portion in which 6 eligible subjects will be enrolled and treated for at least one 3-week cycle to determine if the safety profile of FLX475+ipilimumab is acceptable to complete enrollment of the approximately 20-subject study.
Interventions
DRUGFLX475
Tablet
DRUGIpilimumab
IV infusion
Sponsors
RAPT Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage IV or unresectable Stage III advanced melanoma * Prior treatment with at least 2 months of anti-PD-(L)1 agent * Measurable disease at baseline * Tumor available for biopsy
Exclusion criteria
* History of allergy or severe hypersensitivity to biologic agents * History of Grade 3-4 immune-related adverse events leading to discontinuation of prior immunotherapy * Prior treatment with ipilimumab or other (cytotoxic T-lymphocyte-associated antigen 4) CTLA-4 antagonists
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Approximately 1 year | To evaluate the objective response rate (ORR), defined as confirmed complete or partial response per RECIST 1.1, of FLX475 in combination with ipilimumab in subjects with advanced melanoma previously treated with an anti-PD-1 or anti-PD-L1 agent |
| Safety and Tolerability as Measured by Number of Participants That Experienced Other Adverse Events | Approximately 3 weeks | Number of participants that experienced Other Adverse Events |
| Safety and Tolerability as Measured by Number of Participants That Experienced Serious Adverse Events | Approximately 3 weeks | Number of participants that experienced Serious Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic (PD) Markers | Approximately 1 year | To assess the effects of FLX475 in combination with ipilimumab on pharmacodynamic (PD) markers relating to drug mechanism of action |
| Progression-free Survival | Approximately 1 year | To evaluate the progression-free survival (PFS) of subjects with advanced melanoma treated with FLX475 in combination with ipilimumab who have been previously treated with an anti-PD-1 or anti-PD-L1 agent |
| Tumor Control | Approximately 1 year | To characterize the onset, magnitude, and duration of tumor control in subjects receiving FLX475 in combination with ipilimumab |
| Overall Survival (OS) | Approximately 1 year | To evaluate the overall survival (OS) of subjects with advanced melanoma treated with FLX475 in combination with ipilimumab who have been previously treated with an anti-PD-1 or anti-PD-L1 agent |
| Plasma Concentrations of FLX475 | Approximately 1 year | To evaluate the plasma concentrations of FLX475 when it is given in combination with ipilimumab |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FLX475 and Ipilimumab Combination Therapy Participants received FLX475 tablets orally and ipilimumab by IV infusions
FLX475: Tablet
Ipilimumab: IV infusion | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | FLX475 and Ipilimumab Combination Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 4 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 | 1 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 5 / 6 |
Outcome results
Primary
Objective Response Rate
To evaluate the objective response rate (ORR), defined as confirmed complete or partial response per RECIST 1.1, of FLX475 in combination with ipilimumab in subjects with advanced melanoma previously treated with an anti-PD-1 or anti-PD-L1 agent
Time frame: Approximately 1 year
Population: This outcome was not measured as the study was prematurely terminated for reasons unrelated to safety,
Primary
Safety and Tolerability as Measured by Number of Participants That Experienced Other Adverse Events
Number of participants that experienced Other Adverse Events
Time frame: Approximately 3 weeks
Population: Participants received FLX475 tablets orally and ipilimumab by IV infusions
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FLX475 and Ipilimumab Combination Therapy | Safety and Tolerability as Measured by Number of Participants That Experienced Other Adverse Events | 6 Participants |
Primary
Safety and Tolerability as Measured by Number of Participants That Experienced Serious Adverse Events
Number of participants that experienced Serious Adverse Events
Time frame: Approximately 3 weeks
Population: Participants received FLX475 tablets orally and ipilimumab by IV infusions
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FLX475 and Ipilimumab Combination Therapy | Safety and Tolerability as Measured by Number of Participants That Experienced Serious Adverse Events | 5 Participants |
Secondary
Overall Survival (OS)
To evaluate the overall survival (OS) of subjects with advanced melanoma treated with FLX475 in combination with ipilimumab who have been previously treated with an anti-PD-1 or anti-PD-L1 agent
Time frame: Approximately 1 year
Population: All participants who received the study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FLX475 and Ipilimumab Combination Therapy | Overall Survival (OS) | 3 Participants |
Secondary
Pharmacodynamic (PD) Markers
To assess the effects of FLX475 in combination with ipilimumab on pharmacodynamic (PD) markers relating to drug mechanism of action
Time frame: Approximately 1 year
Population: This outcome was not measured as the study was prematurely terminated for reasons unrelated to safety.
Secondary
Plasma Concentrations of FLX475
To evaluate the plasma concentrations of FLX475 when it is given in combination with ipilimumab
Time frame: Approximately 1 year
Population: This outcome was not measured as the study was prematurely terminated for reasons unrelated to safety,
Secondary
Progression-free Survival
To evaluate the progression-free survival (PFS) of subjects with advanced melanoma treated with FLX475 in combination with ipilimumab who have been previously treated with an anti-PD-1 or anti-PD-L1 agent
Time frame: Approximately 1 year
Population: This outcome was not measured as the study was prematurely terminated for reasons unrelated to safety.
Secondary
Tumor Control
To characterize the onset, magnitude, and duration of tumor control in subjects receiving FLX475 in combination with ipilimumab
Time frame: Approximately 1 year
Population: This outcome was not measured as the study was prematurely terminated for reasons unrelated to safety.