Solid Tumor, Adult
Conditions
Keywords
solid tumor, Pembrolizumab,
Brief summary
Phase II trial in which patients with metastatic solid tumors experiencing progression after first line standard chemotherapy or for which there is no standard chemotherapy, and for which pembrolizumab does not have an FDA or compendia listing approved indication, will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.
Detailed description
Patients with metastatic or recurrent solid malignancy who have progressed on first line standard of care treatment or for which defined standard of care does not exist or is not readily available are eligible to participate on this trial. Patients for which pembrolizumab has an FDA approved indication and for whom pembrolizumab is covered by their insurance should receive standard commercial pembrolizumab and will not be eligible for this trial. The primary objective of this trial is to evaluate the Immune-Related Objective Response Rate (IR-ORR) achieved with pembrolizumab in patients with Fanconi Anemia Repair Pathway functionally competent and functionally deficient tumors. Trial treatment should be administered on Day 1 of each cycle after all procedures/assessments have been completed. Trial treatment may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons. All trial treatments will be administered on an outpatient basis. Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Target infusion timing is 30 minutes. Expansion Cohort: Ten (10) additional subjects with the diagnosis of metastatic or recurrent endometrial carcinoma will be enrolled in the trial at the conclusion of regular enrollment.
Interventions
Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle
Sponsors
Merck Sharp & Dohme LLC
Miami Cancer Institute
Baptist Health South Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible participants will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Have measurable disease based on RECIST 1.1. * Be willing to provide consent for retrieval of archival tumor material tissue from a previously obtained core or excisional biopsy of a tumor lesion. * Have a tumor presentation at screening for which pembrolizumab does not have an FDA approved indication for commercial use. * Have a performance status of 0, 1 or 2 on the ECOG Performance Scale. * Demonstrate adequate organ function * Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. Expansion cohort - additional criteria 1. Diagnosis of Endometrial Carcinoma or Sarcoma which is metastatic and has failed standard treatment or is recurrent, or for which standard chemotherapy is contraindicated or refused by patient. 2. Sufficient tissue is available for correlative studies 3. MSI studies have been performed, either by immunohistochemistry or next generation sequencing and results show that patient is MS low or stable.
Exclusion criteria
* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of treatment. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * Has a known history of active Bacillus Tuberculosis * Hypersensitivity to pembrolizumab or any of its excipients. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). * Has immunohistochemically proven mismatch repair deficient cancer * Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis * Evidence of interstitial lung disease. * Has an active infection requiring systemic therapy. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immune-related Objective Response Rate | 20 weeks | Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy, defined as the percent of participants who achieved complete or partial response. Per irRC, for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all lesions in two consecutive observations not less than 4 weeks apart; Partial Response (PR), ≥50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 20 weeks | Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy. PFS will be defined as the time from treatment start to time of disease progression or death, whichever comes first. Per irRC, for target lesions assessed by CT or MRI: Progressive Disease (PD), at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart. |
| Overall Response | 3 years | Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy, defined as the duration of time from start of treatment to end of study or death, whichever comes first. Per irRC, for target lesions assessed by CT or MRI:Complete Response (CR) is the disappearance of all lesions in two consecutive observations not less than 4 weeks apart; Partial Response (PR) is a ≥50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; and Progressive Disease (PD) is at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart. Everything else is considered Stable Disease (SD). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab 200 mg Q3W Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle
Pembrolizumab 200 mg Q3W: Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle | 52 |
| Total | 52 |
Baseline characteristics
| Characteristic | Pembrolizumab 200 mg Q3W |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 28 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 66 years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 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 | 45 Participants |
| Region of Enrollment United States | 52 participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 38 / 52 |
| other Total, other adverse events | 30 / 52 |
| serious Total, serious adverse events | 19 / 52 |
Outcome results
Primary
Immune-related Objective Response Rate
Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy, defined as the percent of participants who achieved complete or partial response. Per irRC, for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all lesions in two consecutive observations not less than 4 weeks apart; Partial Response (PR), ≥50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart.
Time frame: 20 weeks
Population: Two participants were excluded from analysis: one was deemed not response-evaluable after a further review of baseline CT images demonstrated not clearly measurable disease; another deteriorated rapidly due to tumor progression within a week of the first dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab 200 mg Q3W | Immune-related Objective Response Rate | 9 Participants |
Secondary
Overall Response
Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy, defined as the duration of time from start of treatment to end of study or death, whichever comes first. Per irRC, for target lesions assessed by CT or MRI:Complete Response (CR) is the disappearance of all lesions in two consecutive observations not less than 4 weeks apart; Partial Response (PR) is a ≥50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; and Progressive Disease (PD) is at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart. Everything else is considered Stable Disease (SD).
Time frame: 3 years
Population: Two participants were excluded from analysis: one was deemed not response-evaluable after a further review of baseline CT images demonstrated not clearly measurable disease; another deteriorated rapidly due to tumor progression within a week of the first dose of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg Q3W | Overall Response | 10.9 months |
Secondary
Progression-free Survival (PFS)
Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy. PFS will be defined as the time from treatment start to time of disease progression or death, whichever comes first. Per irRC, for target lesions assessed by CT or MRI: Progressive Disease (PD), at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart.
Time frame: 20 weeks
Population: Two participants were excluded from analysis: one was deemed not response-evaluable after a further review of baseline CT images demonstrated not clearly measurable disease; another deteriorated rapidly due to tumor progression within a week of the first dose of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab 200 mg Q3W | Progression-free Survival (PFS) | 2.9 months |