Desmoplastic Melanoma
Conditions
Brief summary
This pilot phase II trial studies how well pembrolizumab works in treating patients with desmoplastic melanoma (DM) that can be removed by surgery (resectable) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the pathologic complete response rate (pCR) in patients with resectable desmoplastic melanoma treated with neoadjuvant pembrolizumab (MK-3475). (Cohort A) II. To evaluate the complete response rate (confirmed and unconfirmed) in patients with unresectable desmoplastic melanoma treated with pembrolizumab (MK-3475). (Cohort B) SECONDARY OBJECTIVES: I. To estimate the 9 week response rate (RR) (unconfirmed complete and partial responses) among patients with measurable disease. (Cohort A) II. To estimate the median overall survival (OS). (Cohort A) III. To evaluate safety and tolerability of pembrolizumab (MK-3475) in the neoadjuvant setting. (Cohort A) IV. To estimate the median progression-free survival (PFS). (Cohort B) V. To estimate the median overall survival (OS). (Cohort B) VI. To evaluate safety and tolerability of pembrolizumab (MK-3475) in this setting. (Cohort B) OTHER OBJECTIVES: I. To evaluate the hypothesis that higher mutational load in the patient derived baseline tumor biopsy samples is associated with higher pathologic complete response (pCR). II. To evaluate T cell infiltration into the tumors and circulating tumor deoxyribonucleic acid (DNA) profile from blood samples in DM patients and correlate with response to programmed cell death protein 1 (PD-1) blockade. III. To evaluate the clonality of tumor infiltrating T cells in DM patients and correlate with response to PD-1 blockade. IV. To evaluate adaptive immune resistant mechanism in DM tumors. OUTLINE: Patients are enrolled to 1 of 2 cohorts. COHORT A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab. COHORT B: Patients with unresectable disease receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity. Patients undergo computed tomography (CT) scan and may undergo position emission tomography (PET) and magnetic resonance imaging (MRI) throughout the study. Patients also undergo blood sample collection at screening and tumor biopsy throughout the study. After completion of study treatment, patients are followed up at 6 weeks after the last dose, then every 12 weeks to the end of the first year, then every 6 months to the end of the fifth year after registration. After progression, patients are followed every 6 months for up to 2 years from the date of registration, then annually thereafter until 5 years from registration.
Interventions
PROCEDUREBiopsy Procedure
Undergo tumor biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREComputed Tomography
Undergo CT scan
PROCEDUREMagnetic Resonance Elastography
Undergo MRI
BIOLOGICALPembrolizumab
Given IV
PROCEDUREPositron Emission Tomography
Undergo PET scan
PROCEDURETherapeutic Conventional Surgery
Undergo surgical resection
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* COHORT A: Patients must have histologically or cytologically confirmed primary desmoplastic melanoma that is deemed resectable; the decision to perform surgery on patients must be based on good clinical judgment; eligible patients for surgical resection must have disease that, in the judgment of the surgeon, is deemed completely resectable resulting in free surgical margins; patients must have residual disease after initial biopsy which can be measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; residual disease can either be confirmed with fine-needle aspiration (FNA) or if measurable disease is present, no FNA needs to be obtained OR * COHORT B: Patients must have histologically or cytologically confirmed primary desmoplastic melanoma that is unresectable; patients in Cohort B must have measurable disease per RECIST 1.1 * Contrast-enhanced computed tomography (CT) scans of the chest, abdomen and pelvis are required; a whole body positron emission tomography (PET)/CT scan with diagnostic quality images and intravenous iodinated contrast may be used in lieu of a contrast enhanced CT of the chest, abdomen and pelvis; imaging of the head and neck is required only if the patient has a head/neck primary; contrast may be omitted if the treating investigator believes that exposure to contrast poses an excessive risk to the patient; if skin lesions are being followed as measurable disease, photograph with a ruler included and physician measurements, must be kept in the patient's chart as source documentation; all measurable lesions must be assessed within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the baseline tumor assessment form (RECIST 1.1) * Patients must not have known brain metastases unless brain metastases have been treated and patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 14 days prior to registration * Patients must not have received prior systemic treatment for this melanoma * Patients must not be planning to receive concomitant other biologic therapy, hormonal therapy, other chemotherapy, anti-cancer surgery or other anti-cancer therapy while on this protocol * Patients must not have received radiation therapy, non-cytotoxic agents or investigational agents or systemic corticosteroids within 14 days prior to registration * Patients may have received prior surgery; all adverse events associated with prior surgery must have resolved to =\< grade 1 (per Common Terminology Criteria for Adverse Events \[CTCAE\] 4.0) prior to registration * Patients must be \>= 18 years of age * Absolute neutrophil count (ANC) \>= 1,500/mcl (obtained within 28 days prior to registration) * Platelets \>= 50,000/mcl (obtained within 28 days prior to registration) * Hemoglobin \>= 8 g/dL (obtained within 28 days prior to registration) * Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (or =\< 3.0 x IULN with Gilbert's syndrome) (obtained within 28 days prior to registration) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN (or \< 5 x IULN for patients with known liver metastases) (obtained within 28 days prior to registration) * Patients must have lactate dehydrogenase (LDH) performed within 28 days prior to registration * Patients must have Zubrod performance status =\< 2 * Patients must not have history of (non-infectious) pneumonitis that required steroids or current pneumonitis * Patients must not have an active infection requiring systemic therapy * Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment * Patients must not have received live vaccines within 42 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed * Patients known to be human immunodeficiency virus (HIV) positive prior to registration are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate CD4 counts (\>= 350 mm\^3), and serum HIV viral load of \< 25,000 IU/ml; patients must be on a stable anti-viral therapy * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated in situ cancer, adequately treated stage I or II cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years * Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing due to unknown teratogenic side effects * Patients must have specimens available and institutions must be planning to submit for centralized pathology review and for integrated translational medicine objectives * Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * As a part of the Oncology Patient Enrollment Network (OPEN) registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate (Cohort A) | Up to 5 years | Pathologic complete response is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standard of care. |
| Complete Response (CR) Rate (Cohort B) | Up to 5 years | Complete response (per RECIST 1.1) defined as: disappearance of all target and non-target lesions no new lesions, no disease related symptoms, and any lymph nodes must have reduction in short axis to \< 1.0 cm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 9 Week Response Rate (Cohort A) | Up to 3 months | Unconfirmed complete (CR) and partial responses (PR) at end of neoadjuvant treatment assessment among patients with measurable disease. CR and PR per response evaluation criteria in solid tumors (RECIST v1.1): CR is complete disappearance of all target and non-target lesions, no new lesions, no disease related symptoms, and lymph nodes must have reduction in short axis to \<1.0cm. PR is greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Overall response = CR + PR. |
| Overall Survival (Cohort A and B) | Up to 5 years | From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. |
| Progression Free Survival (Cohort B) | Up to 5 years | From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm, unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided), appearance of any new lesion/site, or death due to disease without prior documentation of progression and without symptomatic deterioration |
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duration of treatment and follow-up until death or 5 years post registration. | Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 4.0 was used for all AE reporting. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKari L Kendra
SWOG Cancer Research Network
Participant flow
Pre-assignment details
57 participants were enrolled, but one participant from Cohort A withdrew consent prior to receiving protocol treatment and is not analyzable.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Resectable - Pembrolizumab, Surgery Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab. | 29 |
| Cohort B: Unresectable - Pembrolizumab Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity. | 27 |
| Total | 56 |
Baseline characteristics
| Characteristic | Cohort B: Unresectable - Pembrolizumab | Total | Cohort A: Resectable - Pembrolizumab, Surgery |
|---|---|---|---|
| Age, Customized Age | 75.2 years | 74.9 years | 74.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 52 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| M Stage M0 | 8 Participants | 37 Participants | 29 Participants |
| M Stage M1a | 1 Participants | 1 Participants | 0 Participants |
| M Stage M1b | 11 Participants | 11 Participants | 0 Participants |
| M Stage M1c | 7 Participants | 7 Participants | 0 Participants |
| N Stage N0 | 12 Participants | 36 Participants | 24 Participants |
| N Stage N1b | 2 Participants | 4 Participants | 2 Participants |
| N Stage N2a | 1 Participants | 1 Participants | 0 Participants |
| N Stage N2b | 2 Participants | 2 Participants | 0 Participants |
| N Stage N2c | 1 Participants | 4 Participants | 3 Participants |
| N Stage N3 | 2 Participants | 2 Participants | 0 Participants |
| N Stage NX | 4 Participants | 4 Participants | 0 Participants |
| N Stage Unknown | 3 Participants | 3 Participants | 0 Participants |
| Performance Status 0 | 19 Participants | 41 Participants | 22 Participants |
| Performance Status 1 | 8 Participants | 15 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 27 Participants | 55 Participants | 28 Participants |
| Sex: Female, Male Female | 2 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 25 Participants | 47 Participants | 22 Participants |
| T Stage T0 | 2 Participants | 2 Participants | 0 Participants |
| T Stage T1a | 1 Participants | 2 Participants | 1 Participants |
| T Stage T1b | 0 Participants | 2 Participants | 2 Participants |
| T Stage T2a | 1 Participants | 7 Participants | 6 Participants |
| T Stage T2b | 1 Participants | 2 Participants | 1 Participants |
| T Stage T3a | 4 Participants | 11 Participants | 7 Participants |
| T Stage T3b | 2 Participants | 3 Participants | 1 Participants |
| T Stage T4a | 8 Participants | 16 Participants | 8 Participants |
| T Stage T4b | 5 Participants | 7 Participants | 2 Participants |
| T Stage Tis | 1 Participants | 1 Participants | 0 Participants |
| T Stage Tx | 0 Participants | 1 Participants | 1 Participants |
| T Stage Unknown | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 29 | 10 / 27 |
| other Total, other adverse events | 23 / 29 | 25 / 27 |
| serious Total, serious adverse events | 1 / 29 | 14 / 27 |
Outcome results
Primary
Complete Response (CR) Rate (Cohort B)
Complete response (per RECIST 1.1) defined as: disappearance of all target and non-target lesions no new lesions, no disease related symptoms, and any lymph nodes must have reduction in short axis to \< 1.0 cm.
Time frame: Up to 5 years
Population: All eligible and analyzable participants with measurable disease at baseline (n=27).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Resectable - Pembrolizumab, Surgery | Complete Response (CR) Rate (Cohort B) | 37 percentage of participants |
Comparison: We assumed a null CR rate of 5% and powered the study assuming an alternative hypothesis of 20%. This single stage design had an alpha of 8.5% (i.e. probability of declaring the regimen warrants further study when the true CR is 5%) and a power of 82% (probability of declaring the regimen warrants further study when the true CR is 20%) with 21 eligible participants.p-value: <0.001One-sided Exact Binomial
Primary
Pathologic Complete Response (pCR) Rate (Cohort A)
Pathologic complete response is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standard of care.
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Resectable - Pembrolizumab, Surgery | Pathologic Complete Response (pCR) Rate (Cohort A) | 55 percentage of participants |
Comparison: We assumed a null pCR rate of 5% and powered the study assuming an alternative hypothesis of 25%. This single stage design had an alpha of 3.4% (i.e. probability of declaring the regimen warrants further study when the true CR is 5%) and a power of 90% (probability of declaring the regimen warrants further study when the true pCR is 25%) with 25 eligible participants.p-value: <0.001One-sided Exact Binomial
Secondary
9 Week Response Rate (Cohort A)
Unconfirmed complete (CR) and partial responses (PR) at end of neoadjuvant treatment assessment among patients with measurable disease. CR and PR per response evaluation criteria in solid tumors (RECIST v1.1): CR is complete disappearance of all target and non-target lesions, no new lesions, no disease related symptoms, and lymph nodes must have reduction in short axis to \<1.0cm. PR is greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Overall response = CR + PR.
Time frame: Up to 3 months
Population: All eligible and analyzable participants with measurable disease at baseline (n=26).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Resectable - Pembrolizumab, Surgery | 9 Week Response Rate (Cohort A) | 46 percentage of participants |
Secondary
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 4.0 was used for all AE reporting.
Time frame: Duration of treatment and follow-up until death or 5 years post registration.
Population: Participants who were eligible and received at least one dose of protocol treatment. 29 participants were evaluable or AEs in Cohort A and 27 were evaluable or AEs in Cohort B.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Back pain | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Immune system disorders - Other, specify | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | CPK increased | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 1 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 1 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Musculoskeletal and connective tiss disorder - Other | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myositis | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pancreatitis | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adrenal insufficiency | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Upper gastrointestinal hemorrhage | 0 Participants |
| Cohort A: Resectable - Pembrolizumab, Surgery | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 0 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Upper gastrointestinal hemorrhage | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sepsis | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Skin and subcutaneous tissue disorders - Other | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Adrenal insufficiency | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Back pain | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | CPK increased | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Colitis | 2 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 2 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Immune system disorders - Other, specify | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lipase increased | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Musculoskeletal and connective tiss disorder - Other | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Myositis | 1 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pancreatitis | 2 Participants |
| Cohort B: Unresectable - Pembrolizumab | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 2 Participants |
Secondary
Overall Survival (Cohort A and B)
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Resectable - Pembrolizumab, Surgery | Overall Survival (Cohort A and B) | NA months |
| Cohort B: Unresectable - Pembrolizumab | Overall Survival (Cohort A and B) | 50.6 months |
Secondary
Progression Free Survival (Cohort B)
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm, unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided), appearance of any new lesion/site, or death due to disease without prior documentation of progression and without symptomatic deterioration
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Resectable - Pembrolizumab, Surgery | Progression Free Survival (Cohort B) | 49.2 months |
Other Pre-specified
Adaptive Immune Resistant Mechanism (Cohort A and B)
Will compare change in PD-L1 expression between responders and non-responders.
Time frame: Up to 5 years
Other Pre-specified
Baseline Mutational Load (Cohort A and B)
Will assess the association between per megabase mutation rate and pCR or CR status.
Time frame: Up to 5 years
Other Pre-specified
Change in T-cell Infiltration (Cohort A and B)
Will compare change in CD8 expression following treatment between responders and non-responders.
Time frame: Up to 5 years
Other Pre-specified
Clonality of Tumor Infiltrating T Cells (Cohort A and B)
Will compare change from baseline in TCR clonality metric between responders and non-responders.
Time frame: Up to 5 years
Other Pre-specified
ctDNA Fraction
Will assess the association between response and ctDNA fraction.
Time frame: Up to 5 years