| Eligibility |
Study Participant Inclusion Criteria
Inclusion Criteria:
1. Is able to complete signed informed consent. Patients for whom English is not their
primary language are eligible for participation with translator assistance during the
informed consent process.
2. Is of age = 18
3. Is able, in the investigator's judgment, to comply with the study protocol
4. Has measurable disease according to RECIST v1.1 The pleural mesothelioma cohort will
require measurable disease according to either modified RECIST or RECIST; the Hodgkin
lymphoma patients will be assessed by the 2014 Lugano criteria (see Appendix F)
5. Has an ECOG performance status of 0 - 1
6. Has adequate hematologic and end-organ function, defined by the following laboratory
test results, obtained within 14 days prior to initiation of study treatment:
- ANC = 1.0×109/L without granulocyte colony-stimulating factor support (for the
lymphoma cohort only, Absolute neutrophil count of = 1.0×109/L without growth
factor support for 3 days prior to screening assessment.)
- Lymphocyte count = 0.5×109/L
- Platelet count = 100× 109/L without transfusion (for the lymphoma cohort only:
platelet count of = 50×109/L without transfusion for 3 days prior to screening
assessment)
- Hemoglobin = 90 g/L (for the lymphoma cohort only: Hemoglobin >80 g/L without
transfusion for 3 days prior to screening assessment) (For platelet count and
hemoglobin, patients may be transfused to meet either criterion but not within 14
days prior to initiation of study treatment)
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
phosphatase (ALP) = 2.5× upper limit of normal (ULN), with the following
exceptions:
- Patients with documented liver metastases: AST and ALT = 5×ULN
- Patients with documented liver or bone metastases: ALP = 5×ULN
- Serum bilirubin = 1.5 ×ULN with the following exception:
- Serum creatinine = 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault
formula) =50 mL/min OR 24-hour urine creatinine clearance =50 mL/min
- Serum albumin = 2.5 g/dL
- For patients not receiving therapeutic anticoagulation: INR or aPTT = 1.5×ULN
- For patients receiving therapeutic anticoagulation: is on a stable anticoagulant
regimen without changes in agent and / or dose in the past 30 days
7. Must agree to use a highly effective method of birth control (as defined in Section
7.4.1) (female patients and male patients with female partners of childbearing
potential) during and for 6 months after last dose of study treatment. Also see
related information in Section 6.6.10.8.
.
Basket-specific Inclusion Criteria:
1. Peritoneal Mesothelioma: Has advanced MPeM that was previously treated with and
refractory/intolerant to platinum-pemetrexed systemic chemotherapy or has not received
treatment and is ineligible for platinum-pemetrexed treatment
2. Pleural Mesothelioma: Has unresectable MPM and is treatment naïve or has received any
line of prior therapy, including anti-PD1/anti-PDL1/anti-CTLA4.
3. High-grade Neuroendocrine Carcinoma: Has extra-pulmonary site carcinoma (small-cell-
and large-cell lung cancer excluded) and has received therapy with a platinum-based
chemotherapy regimen
4. MSI-H Cancers: Has not had anti-PD1 / anti-PDL1 / anti-CLTA4 therapyMSI-H/dMMR,
locally advanced or metastatic solid tumors. Locally advanced solid tumors are defined
by having =20% chance of recurrence with surgery alone. Patients with localized solid
tumors are also eligible if they have a high risk for surgical mortality defined as
>5% by ACS National Surgery Quality Improvement Program. Patients being treated with
neoadjuvant intent may be treated for up to 6 months prior to surgical resection,
though in patients with clear clinical benefit as deemed by treating physicians, a
non-operative approach-treatment duration = 6 months (and up to 2 years)-may be
considered.
Note: ASC = American College of Surgeons, MSI-H = microsatellite instability-high,
dMMR = deficient mismatch repair.
5. Lymphoma: Has relapsed, refractory classical Hodgkin lymphoma and has received
first-line chemotherapy. Prior treatment with anti-PD1 / PDL1 antibody is not
exclusionary.
6. Cervical Cancer: Has recurrent, metastatic, or persistent cervical cancer (squamous
cell carcinoma, adenosquamous, or adenocarcinoma of the cervix) and has received at
least one prior line of systemic therapy and not amenable to curative treatment. Prior
treatment with anti-PD1 / PDL1 antibody is not exclusionary.
7. Small-cell lung cancer: Extensive-stage small-cell lung cancer following treatment
with prior platinum-based therapy, which can include prior anti-PD1, anti-PDL1, but
not anti-CTLA4.
Study Participant Exclusion Criteria:
Participants who meet any of the following criteria will be excluded from the study:
1. Received treatment for the studied cancer within 21 days prior to initiation of study
treatment
2. Received treatment with targeted therapies or investigational therapies within 21 days
or for the duration of 5 half-lives prior to initiation of study treatment
3. Has a history of severe allergic, anaphylactic, or other hypersensitivity reactions to
study drug
4. Has active known- or suspected autoimmune disease (allowed are patients with vitiligo;
type 1 diabetes mellitus, or residual hypothyroidism due to an autoimmune condition
that is treatable with hormone-replacement therapy only; psoriasis, atopic dermatitis,
or another autoimmune skin condition that is managed without systemic therapy; or
arthritis that is managed without systemic therapy beyond oral acetaminophen and
non-steroidal anti-inflammatory drugs).
5. Has any condition that requires systemic treatment with corticosteroids, prednisone
equivalents, or other immunosuppressive medications within 14 days prior to first dose
of study drug (except that inhaled or topical corticosteroids or brief courses of
corticosteroids given for prophylaxis of contrast dye allergic response are
permitted).
6. Has a history or evidence of any other clinically unstable/uncontrolled disorder,
condition, or disease (including, but not limited to, cardiopulmonary-, renal-,
metabolic-, hematologic-, or psychiatric-) other than their primary malignancy, that
in the opinion of the Investigator would pose a risk to patient safety or interfere
with study evaluations, procedures, or completion.
7. Has had any serious bacterial, viral, parasitic, or systemic fungal infections within
14 days prior to the first dose of study drug.
8. Received prior treatment with any checkpoint-inhibitor therapy regimen that targets
PD1/PDL1 or CTLA-4 (this does not apply to candidates for the lymphoma, pleural
mesothelioma, cervical cancer or SCLC cohorts-see basket-specific inclusion criteria).
9. Received a live-virus vaccine within 30 days prior to first dose of study drug
(vaccines that do not contain live virus are permitted).
10. Has another malignancy, except for non-melanoma skin cancer, in situ cervical cancer,
or bladder cancer (Tis and T1) that has been adequately treated during the 3 years
prior to screening (Note: For MSI-H cohort, prior history of malignancies are allowed
unless this may be a competing risk for mortality while on study per the
investigator).
11. Has untreated or unstable brain metastases. Allowed are those with known brain
metastases who have been previously treated and are asymptomatic. If prior local
therapy was received, it must have been completed at least 14 days prior to receiving
study drug.
12. Has evidence of current ILD or pneumonitis or a prior history of ILD or non-infectious
pneumonitis requiring high-dose glucocorticoids
13. Is breastfeeding or plans to initiate breastfeeding during the study treatment or
within 6 months of taking study treatment.
|
