Vudalimab for the Treatment of Advanced Rare Cancers

Inclusion Criteria

• 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
• Is of age >= 18
• Is able, in the investigator’s judgment, to comply with the study protocol
• 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
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L without granulocyte colony-stimulating factor support (within 14 days prior to initiation of study treatment)
• Lymphocyte count >= 0.5 x 10^9/L (within 14 days prior to initiation of study treatment)
• Platelet count >= 100 x 10^9/L without transfusion (within 14 days prior to initiation of study treatment)
• Hemoglobin >= 90 g/L (within 14 days prior to initiation of study treatment) (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 x upper limit of normal (ULN) (within 14 days prior to initiation of study treatment), with the following exceptions: * Patients with documented liver metastases: AST and ALT =< 5 x ULN * Patients with documented liver or bone metastases: ALP =< 5 x ULN
• Serum bilirubin =< 1.5 x ULN (within 14 days prior to initiation of study treatment) with the following exception: * Patients with known Gilbert disease: serum bilirubin level =< 3 x ULN
• 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 (within 14 days prior to initiation of study treatment)
• Serum albumin >= 2.5 g/dL (within 14 days prior to initiation of study treatment)
• For patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or a partial thromboplastin time (PTT) =< 1.5 x ULN (within 14 days prior to initiation of study treatment)
• For patients receiving therapeutic anticoagulation: is on a stable anticoagulant regimen without changes in agent and/or dose in the past 30 days
• Must agree to use a highly effective method of birth control (female patients and male patients with female partners of childbearing potential) during and for 6 months after last dose of study treatment
• Peritoneal mesothelioma: Has advanced malignant peritoneal mesothelioma (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
• Pleural mesothelioma: Has unresectable malignant pleural mesothelioma (MPM) and is treatment naive or has received any line of prior therapy, including anti-PD1/anti-PDL1
• 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
• Microsatellite instability-high (MSI-H) cancers: Has not had anti-PD1 / anti-PDL1 / anti-CLTA4 therapy, non-colorectal- or colorectal- (the latter limited to =< 25% of total accrual) MSI-H/deficient mismatch repair (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 American College of Surgeons (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
• Lymphoma: Has relapsed, refractory classical Hodgkin lymphoma and has received first-line chemotherapy
• 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 that may include pembrolizumab (chemotherapy administered as part of chemoradiation does not count) and not amenable to curative treatment
• 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

Exclusion Criteria

• Received treatment for the studied cancer within 21 days prior to initiation of study treatment
• 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
• Has a history of severe allergic, anaphylactic, or other hypersensitivity reactions to study drug
• 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)
• 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)
• 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
• Has had any serious bacterial, viral, parasitic, or systemic fungal infections within 14 days prior to the first dose of study drug
• Received prior treatment with any checkpoint-inhibitor therapy regimen that targets PD1/PDL1 or CTLA-4 (this does not apply to candidates for the pleural mesothelioma, cervical cancer or SCLC cohorts)
• Received a live-virus vaccine within 30 days prior to first dose of study drug (vaccines that do not contain live virus are permitted)
• 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).
• 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
• Is breastfeeding or plans to initiate breastfeeding during the study treatment or within 6 months of taking study treatment