Advanced Malignant Solid Neoplasm, Carcinoma of Unknown Primary, Metastatic Adrenal Gland Pheochromocytoma, Metastatic Kidney Medullary Carcinoma, Metastatic Malignant Germ Cell Tumor, Metastatic Malignant Solid Neoplasm, Metastatic Paraganglioma, Metastatic Penile Carcinoma, Metastatic Skin Squamous Cell Carcinoma, Small Cell Carcinoma, Stage III Adrenal Cortex Carcinoma AJCC v7, Stage IV Adrenal Cortex Carcinoma AJCC v7, Stage IV Penile Cancer AJCC v7, Stage IV Renal Cell Cancer AJCC v7, Unresectable Adrenal Gland Pheochromocytoma, Unresectable Paraganglioma, Unresectable Skin Squamous Cell Carcinoma, Unresectable Solid Neoplasm, Vascular Neoplasm
Conditions
Brief summary
This phase II trial studies how well pembrolizumab works in treating patients with rare tumors that cannot be removed by surgery or have spread to other parts of the body. Monoclonal antibodies, such as pembrolizumab, may block specific proteins found on white blood cells which may strengthen the immune system and control tumor growth.
Detailed description
PRIMARY OBJECTIVES: I. To obtain early indication of efficacy by evaluation of non-progression rate (NPR) at 27 weeks as defined as the percentage of patients who are alive and progression-free at 27 weeks as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 or immune-related(ir)RECIST or method of tumor evaluation criteria best suitable and accepted for the tumor type evaluated in patients with advanced tumor types receiving pembrolizumab. SECONDARY OBJECTIVES: I. To correlate efficacy by evaluation of tumor size to programmed cell death 1 ligand 1 (PD-L1) status among patients with advanced tumor types receiving pembrolizumab. II. To evaluate safety and tolerability of pembrolizumab in patients with advanced tumors. III. To evaluate the percentage of patients with objective response (complete response \[CR\] or partial response \[PR\]), clinical benefit (CR, PR, or stable disease \[SD\] \>= 4 months), progression free survival (PFS), overall survival (OS), and duration of response (DOR) as assessed by RECIST v1.1 in patients with advanced tumor types receiving pembrolizumab. IV. To evaluate the percentage of patients with objective response (CR or PR), clinical benefit (CR, PR, or SD \>= 4 months), PFS, and DOR as assessed by irRECIST in patients with advanced tumor types receiving pembrolizumab. V. To correlate the NPR at 27 weeks (9 cycles), objective response (CR or PR), clinical benefit CR, PR, or SD \>= 4 months), PFS, OS, and DOR to PD-L1 status among patients with advanced tumor types receiving pembrolizumab. EXPLORATORY OBJECTIVES: I. To evaluate the potential role of tumor-associated immune biomarkers for prediction of therapy effectiveness in patients with advanced tumor types receiving pembrolizumab. II. To correlate the potential role of tumor-associated immune biomarkers for prediction of therapy effectiveness to PD-L1 status among patients with advanced tumor types receiving pembrolizumab. III. To identify imaging characteristics associated with immunological changes in tumor following treatment with pembrolizumab. IV. To compare tumor mutation burden and serial assessment of mutation status in biopsies obtained at baseline and progression in patients with advanced tumor types receiving pembrolizumab. V. To evaluate patient-reported outcomes (PRO) utilizing the National Cancer Institute (NCI) Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaires. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression or toxicity. Patients with clinical response or disease stabilization may continue treatment for up to an additional 12 months. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALPembrolizumab
Given IV
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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
* Be willing and able to provide written informed consent/assent for the trial * Have measurable disease based on RECIST 1.1 or irRECIST; only cohort 9 and 10 can have evaluable disease (non-measurable lesions); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions; patients may have bone metastatic disease evaluable according to tumor evaluation criteria best suitable and accepted for the tumor type evaluated * Have one of the following advanced (unresectable and/or metastatic) solid tumor indications that has progressed following standard therapies, where standard therapies are available: * Squamous cell carcinoma of the skin * Small cell malignancies of non-pulmonary origin * Adrenocortical carcinoma * Medullary renal cell carcinoma * Carcinoma of unknown primary * Penile carcinoma * Vascular sarcoma * Germ cell tumor * Paraganglioma-pheochromocytoma * Other rare tumors (except those tumor types listed in exclusion) * Have failed prior treatment within 6 months of consent date * Have biopsiable disease; subjects must have at least one lesion amenable to biopsy; tumor lesions used for biopsy should not be lesions used as target lesions; in cohort 9: paraganglioma-pheochromocytoma or cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease * Be willing to provide archival tissue; if archival tissue is not available, or a newly obtained core or excisional biopsy of a tumor lesion will be obtained; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; in cohort 9: paraganglioma-pheochromocytoma or cohort 10, where there is prominent bony disease, biopsies may not be possible due to the nature of the disease * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale * Absolute neutrophil count (ANC) \>= 1,000/mcL (performed within 28 days of treatment initiation) * Platelets \>= 75,000/mcL (performed within 28 days of treatment initiation) * Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 28 days of treatment initiation) * Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 X upper limit of normal (ULN) OR \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (performed within 28 days of treatment initiation) * Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (performed within 28 days of treatment initiation) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases (performed within 28 days of treatment initiation) * Albumin \> 2.5 mg/dL (performed within 28 days of treatment initiation) * International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation) * Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation) * 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; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy * For subjects in cohort 2 (small cell malignancies of non-pulmonary origin), confirmation of no brain metastases via imaging
Exclusion criteria
* Is currently participating and receiving study therapy or concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment at the time of administration of first dose of trial treatment; continuation of hormone replacement therapy is permitted; stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a gonadotrophin releasing hormone \[GnRH\] agonist), ovarian, or breast cancer are not exclusionary * 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 history of active TB (bacillus tuberculosis) * Hypersensitivity to pembrolizumab or any of its excipients * Has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy * 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, and diseases for which the treatment could reasonably include pembrolizumab and are not part of the excluded tumor type list or not eligible for the phase I trial * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; 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); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; immunosuppressive corticosteroid doses (\> 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of pembrolizumab; Note: corticosteroids given within 24 hours of an imaging study for purposes of pre-medication in patients with hypersensitivity to radiologic contrast agents are allowed * Has known history of, or any evidence of active, non-infectious pneumonitis * Has an active infection requiring systemic therapy * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator * 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., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] 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 * Is participating in cohort 10 and has melanoma; non-small cell lung cancer; hepatocellular carcinoma; Merkel cell carcinoma; colon or rectal adenocarcinoma; anal canal squamous cell carcinoma; pancreas adenocarcinoma; esophageal squamous cell carcinoma or adenocarcinoma (including gastroesophageal \[GE\] junction); biliary tract adenocarcinoma (gallbladder and biliary tree but excluding ampulla of vater cancers); carcinoid tumors; neuroendocrine carcinomas (well or moderately differentiated pancreatic neuroendocrine tumor); estrogen receptor (ER)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer; triple negative breast cancer; ovarian epithelial, fallopian tube or primary peritoneal carcinoma; endometrial carcinoma; cervical squamous cell cancer; vulvar squamous cell carcinoma; small cell lung cancer; mesothelioma (malignant pleural mesothelioma); thyroid cancer (papillary or follicular subtype); salivary gland carcinoma; nasopharyngeal carcinoma; glioblastoma multiforme; leiomyosarcoma; prostate adenocarcinoma; gastric adenocarcinoma; or small bowel malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-progression Rate (NPR) at 27 Weeks by irRECIST | At 27 weeks | Non-progression rate (NPR) at 27 weeks was defined as the percentage of efficacy evaluable patients who were alive and progression-free at 27 weeks as assessed by irRECIST Progression is defined using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), as an increase ≥ 20% (minimum 5 mm) in total measured tumor burden compared with nadir or progression of non-target lesions or new lesion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years. | Immune-related ORR is defined as the percentage of patients achieving a irCR or irPR based on irRECIST criteria. PD-L1 positivity was defined as Combined Positive Score ≥1. Evaluated objective response in PD-L1 positive patients Per irRECIST: Immune-related (ir) Complete Response (irCR), disappearance of all target and non-target lesions, nodal short axis diameter \<10 mm, no new lesions; irPartial Response (irPR), decrease of ≥30% in tumor burden relative to baseline, non-unequivocal progression of non-target lesions, no new lesions. |
| Number of Patients Who Experienced Treatment-related Adverse Event (TRAE) | First day of administration of study medication through 30 days following last dose, an average of 4 years. | Per protocol, the number and percentage of patients with any treatment-related AE was summarized for all study patients combined. Patients were monitored for AE from the first day of administration of study medication through 30 days following last dose. Each AE (as defined by NCI CTCAE v4.03) was counted only once for a given subject. In the event a patient experienced repeated episodes of the same AE, then the event with the highest severity and/or strongest causal relationship to study treatment was used for purposes of tabulations. |
| Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years. | ORR is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. |
| Clinical Benefit Rate (CBR) Using RECIST v1.1 | Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years. | CBR is defined as the percentage of patients achieving a CR or PR, or stable disease (SD) ≥4 months based on RECIST 1.1 criteria. |
| Progression-free Survival (PFS) Using RECIST v1.1 | Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years. | PFS was defined as the time from administration of the first dose to the first documented disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first. Patients who were alive and had not experienced disease progression at the time of data cutoff were censored. |
| Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years. | Immune-related ORR is defined as the percentage of patients achieving a irCR or irPR based on irRECIST criteria. |
| Immune-related Clinical Benefit Rate (CBR) Using irRECIST | First day of administration of study medication through 30 days following last dose, an average of 4 years. | Immune-related CBR is defined as the percentage of patients achieving a irCR or irPR, or irSD ≥4 months based on irRECIST criteria |
| Immune-related Progression-free Survival (PFS) Using irRECIST | Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks. | Immune-related PFS was defined as the time from administration of the first dose to the first documented disease progression according to irRECIST or death due to any cause, whichever occurs first. Patients who were alive and had not experienced disease progression at the time of data cutoff were censored. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAung Naing
M.D. Anderson Cancer Center
Participant flow
Recruitment details
This is a single-center, open-label, phase II trial of pembrolizumab (MK-3475) in patients with and without programmed death-ligand 1 (PD-L1) positive advanced tumors conducted at the University of Texas MD Anderson Cancer Center
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 20 |
| Cohort 2: Small Cell Malignancies of Nonpulmonary Origin MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 12 |
| Cohort 3: Adrenocortical Carcinoma MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 24 |
| Cohort 4: Medullary Renal Cell Carcinoma MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 5 |
| Cohort 5: Carcinoma of Unknown Primary MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 29 |
| Cohort 6: Penile Carcinoma MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 3 |
| Cohort 7: Vascular Sarcoma MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 11 |
| Cohort 8: Germ Cell Tumor MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 12 |
| Cohort 9: Paraganglioma-pheochromocytoma MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 13 |
| Cohort 10: Other Rare Tumor Histologies MK-3475: 200 mg of MK-3475 administered intravenously on Day 1 of every 21-day cycle | 28 |
| Total | 157 |
Baseline characteristics
| Characteristic | Total | Cohort 2: Small Cell Malignancies of Nonpulmonary Origin | Cohort 3: Adrenocortical Carcinoma | Cohort 4: Medullary Renal Cell Carcinoma | Cohort 5: Carcinoma of Unknown Primary | Cohort 6: Penile Carcinoma | Cohort 1: Squamous Cell Carcinoma of the Skin | Cohort 7: Vascular Sarcoma | Cohort 8: Germ Cell Tumor | Cohort 9: Paraganglioma-pheochromocytoma | Cohort 10: Other Rare Tumor Histologies |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 51 Participants | 2 Participants | 4 Participants | 0 Participants | 14 Participants | 3 Participants | 14 Participants | 6 Participants | 0 Participants | 1 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants | 10 Participants | 20 Participants | 5 Participants | 15 Participants | 0 Participants | 6 Participants | 5 Participants | 12 Participants | 12 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 138 Participants | 9 Participants | 22 Participants | 5 Participants | 25 Participants | 2 Participants | 20 Participants | 11 Participants | 9 Participants | 11 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 118 Participants | 10 Participants | 19 Participants | 1 Participants | 22 Participants | 2 Participants | 20 Participants | 8 Participants | 8 Participants | 10 Participants | 18 Participants |
| Region of Enrollment United States | 157 participants | 12 participants | 24 participants | 5 participants | 29 participants | 3 participants | 20 participants | 11 participants | 12 participants | 13 participants | 28 participants |
| Sex: Female, Male Female | 76 Participants | 7 Participants | 14 Participants | 1 Participants | 21 Participants | 0 Participants | 3 Participants | 4 Participants | 2 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 81 Participants | 5 Participants | 10 Participants | 4 Participants | 8 Participants | 3 Participants | 17 Participants | 7 Participants | 10 Participants | 8 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 114 / 156 |
| other Total, other adverse events | 84 / 156 |
| serious Total, serious adverse events | 72 / 156 |
Outcome results
Primary
Non-progression Rate (NPR) at 27 Weeks by irRECIST
Non-progression rate (NPR) at 27 weeks was defined as the percentage of efficacy evaluable patients who were alive and progression-free at 27 weeks as assessed by irRECIST Progression is defined using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), as an increase ≥ 20% (minimum 5 mm) in total measured tumor burden compared with nadir or progression of non-target lesions or new lesion
Time frame: At 27 weeks
Population: All patients who have received at least 1 dose of study medication with at least 1on-study tumor assessment were included in the analysis. If a patient discontinued before the first radiological assessment due to progression, they were included in the analysis. If the patient discontinued before 27 weeks due to reasons other than progression or death, they were considered non evaluable for this endpoint. One patient enrolled in the ACC cohort was excluded due to change in diagnosis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 7 Participants |
| Cohort 2: Small Cell Malignancies of Nonpulmonary Origin | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 0 Participants |
| Cohort 3: Adrenocortical Carcinoma | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 6 Participants |
| Cohort 4: Medullary Renal Cell Carcinoma | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 0 Participants |
| Cohort 5: Carcinoma of Unknown Primary | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 8 Participants |
| Cohort 6: Penile Carcinoma | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 0 Participants |
| Cohort 7: Vascular Sarcoma | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 2 Participants |
| Cohort 8: Germ Cell Tumor | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 1 Participants |
| Cohort 9: Paraganglioma-pheochromocytoma | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 4 Participants |
| Cohort 10: Other Rare Tumor Histologies | Non-progression Rate (NPR) at 27 Weeks by irRECIST | 9 Participants |
Secondary
Clinical Benefit Rate (CBR) Using RECIST v1.1
CBR is defined as the percentage of patients achieving a CR or PR, or stable disease (SD) ≥4 months based on RECIST 1.1 criteria.
Time frame: Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.
Population: All patients who have received at least 1 dose of study medication with at least one adequate on-study tumor assessment were included in the efficacy analysis. If a patient discontinued the study before the first radiological assessment due to progression of disease, either radiological or clinical, they were considered evaluable and were included in the efficacy analysis. One patient enrolled in the ACC cohort was excluded from the study due to change in the diagnosis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 7 Participants |
| Cohort 2: Small Cell Malignancies of Nonpulmonary Origin | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 0 Participants |
| Cohort 3: Adrenocortical Carcinoma | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 11 Participants |
| Cohort 4: Medullary Renal Cell Carcinoma | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 0 Participants |
| Cohort 5: Carcinoma of Unknown Primary | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 10 Participants |
| Cohort 6: Penile Carcinoma | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 1 Participants |
| Cohort 7: Vascular Sarcoma | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 3 Participants |
| Cohort 8: Germ Cell Tumor | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 2 Participants |
| Cohort 9: Paraganglioma-pheochromocytoma | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 7 Participants |
| Cohort 10: Other Rare Tumor Histologies | Clinical Benefit Rate (CBR) Using RECIST v1.1 | 13 Participants |
Secondary
Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1)
Immune-related ORR is defined as the percentage of patients achieving a irCR or irPR based on irRECIST criteria. PD-L1 positivity was defined as Combined Positive Score ≥1. Evaluated objective response in PD-L1 positive patients Per irRECIST: Immune-related (ir) Complete Response (irCR), disappearance of all target and non-target lesions, nodal short axis diameter \<10 mm, no new lesions; irPartial Response (irPR), decrease of ≥30% in tumor burden relative to baseline, non-unequivocal progression of non-target lesions, no new lesions.
Time frame: Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.
Population: PD-L1 expression on tumor and mononuclear inflammatory cells in tumor nests were assessed on samples obtained prior to treatment. Patients with PD-L1 positive disease (CPS ≥1) were evaluated for objective response.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 6 Participants |
| Cohort 2: Small Cell Malignancies of Nonpulmonary Origin | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 0 Participants |
| Cohort 3: Adrenocortical Carcinoma | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 1 Participants |
| Cohort 4: Medullary Renal Cell Carcinoma | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 0 Participants |
| Cohort 5: Carcinoma of Unknown Primary | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 5 Participants |
| Cohort 6: Penile Carcinoma | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 0 Participants |
| Cohort 7: Vascular Sarcoma | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 1 Participants |
| Cohort 8: Germ Cell Tumor | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 0 Participants |
| Cohort 9: Paraganglioma-pheochromocytoma | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 0 Participants |
| Cohort 10: Other Rare Tumor Histologies | Evaluation of Tumor Size (Objective Response by irRECIST) to PD-L1 Status (CPS ≥1) | 1 Participants |
Secondary
Immune-related Clinical Benefit Rate (CBR) Using irRECIST
Immune-related CBR is defined as the percentage of patients achieving a irCR or irPR, or irSD ≥4 months based on irRECIST criteria
Time frame: First day of administration of study medication through 30 days following last dose, an average of 4 years.
Population: All patients who have received at least 1 dose of study medication with at least one adequate on-study tumor assessment were included in the efficacy analysis. If a patient discontinued the study before the first radiological assessment due to progression of disease, either radiological or clinical, they were considered evaluable and were included in the efficacy analysis. One patient enrolled in the ACC cohort was excluded from the study due to change in the diagnosis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 8 Participants |
| Cohort 2: Small Cell Malignancies of Nonpulmonary Origin | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 0 Participants |
| Cohort 3: Adrenocortical Carcinoma | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 11 Participants |
| Cohort 4: Medullary Renal Cell Carcinoma | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 0 Participants |
| Cohort 5: Carcinoma of Unknown Primary | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 12 Participants |
| Cohort 6: Penile Carcinoma | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 1 Participants |
| Cohort 7: Vascular Sarcoma | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 3 Participants |
| Cohort 8: Germ Cell Tumor | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 2 Participants |
| Cohort 9: Paraganglioma-pheochromocytoma | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 7 Participants |
| Cohort 10: Other Rare Tumor Histologies | Immune-related Clinical Benefit Rate (CBR) Using irRECIST | 14 Participants |
Secondary
Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Immune-related ORR is defined as the percentage of patients achieving a irCR or irPR based on irRECIST criteria.
Time frame: Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.
Population: All patients who have received at least 1 dose of study medication with at least one adequate on-study tumor assessment were included in the efficacy analysis. If a patient discontinued the study before the first radiological assessment due to progression of disease, either radiological or clinical, they were considered evaluable and were included in the efficacy analysis. One patient enrolled in the ACC cohort was excluded from the study due to change in the diagnosis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 6 Participants |
| Cohort 2: Small Cell Malignancies of Nonpulmonary Origin | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 0 Participants |
| Cohort 3: Adrenocortical Carcinoma | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 4 Participants |
| Cohort 4: Medullary Renal Cell Carcinoma | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 0 Participants |
| Cohort 5: Carcinoma of Unknown Primary | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 5 Participants |
| Cohort 6: Penile Carcinoma | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 1 Participants |
| Cohort 7: Vascular Sarcoma | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 1 Participants |
| Cohort 8: Germ Cell Tumor | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 0 Participants |
| Cohort 9: Paraganglioma-pheochromocytoma | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 1 Participants |
| Cohort 10: Other Rare Tumor Histologies | Immune-related ORR Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 5 Participants |
Secondary
Immune-related Progression-free Survival (PFS) Using irRECIST
Immune-related PFS was defined as the time from administration of the first dose to the first documented disease progression according to irRECIST or death due to any cause, whichever occurs first. Patients who were alive and had not experienced disease progression at the time of data cutoff were censored.
Time frame: Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks.
Population: All patients who have received at least 1 dose of study medication with at least one adequate on-study tumor assessment were included in the efficacy analysis. If a patient discontinued the study before the first radiological assessment due to progression of disease, either radiological or clinical, they were considered evaluable and were included in the efficacy analysis. One patient enrolled in the ACC cohort was excluded from the study due to change in the diagnosis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Immune-related Progression-free Survival (PFS) Using irRECIST | 2.3 months |
Secondary
Number of Patients Who Experienced Treatment-related Adverse Event (TRAE)
Per protocol, the number and percentage of patients with any treatment-related AE was summarized for all study patients combined. Patients were monitored for AE from the first day of administration of study medication through 30 days following last dose. Each AE (as defined by NCI CTCAE v4.03) was counted only once for a given subject. In the event a patient experienced repeated episodes of the same AE, then the event with the highest severity and/or strongest causal relationship to study treatment was used for purposes of tabulations.
Time frame: First day of administration of study medication through 30 days following last dose, an average of 4 years.
Population: It was a pre-specified objective. All patients who have received at least 1 dose of study medication were included in the safety analysis. A total of 157 patients were treated on this study. One patient enrolled in the ACC cohort was excluded from the study due to change in the diagnosis following histological assessment of the surgical specimen.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Number of Patients Who Experienced Treatment-related Adverse Event (TRAE) | 88 Participants |
Secondary
Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
ORR is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.
Time frame: Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.
Population: All patients who have received at least 1 dose of study medication with at least one adequate on-study tumor assessment were included in the efficacy analysis. If a patient discontinued the study before the first radiological assessment due to progression of disease, either radiological or clinical, they were considered evaluable and were included in the efficacy analysis. One patient enrolled in the ACC cohort was excluded from the study due to change in the diagnosis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 6 Participants |
| Cohort 2: Small Cell Malignancies of Nonpulmonary Origin | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| Cohort 3: Adrenocortical Carcinoma | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 4 Participants |
| Cohort 4: Medullary Renal Cell Carcinoma | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| Cohort 5: Carcinoma of Unknown Primary | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 5 Participants |
| Cohort 6: Penile Carcinoma | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
| Cohort 7: Vascular Sarcoma | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
| Cohort 8: Germ Cell Tumor | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 0 Participants |
| Cohort 9: Paraganglioma-pheochromocytoma | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 1 Participants |
| Cohort 10: Other Rare Tumor Histologies | Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | 5 Participants |
Secondary
Progression-free Survival (PFS) Using RECIST v1.1
PFS was defined as the time from administration of the first dose to the first documented disease progression according to RECIST v1.1 or death due to any cause, whichever occurs first. Patients who were alive and had not experienced disease progression at the time of data cutoff were censored.
Time frame: Baseline and every 9 weeks thereafter. After 6 months, every 12 weeks at the physician's discretion, if patient has had CR, PR, or SD > 27 weeks, an average of 4 years.
Population: All patients who have received at least 1 dose of study medication with at least one adequate on-study tumor assessment were included in the efficacy analysis. If a patient discontinued the study before the first radiological assessment due to progression of disease, either radiological or clinical, they were considered evaluable and were included in the efficacy analysis. One patient enrolled in the ACC cohort was excluded from the study due to change in the diagnosis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Squamous Cell Carcinoma of the Skin | Progression-free Survival (PFS) Using RECIST v1.1 | 2.2 months |