MC# 17-01 - A Phase I Dose Escalation and Cohort Expansion Study of TSR-042, an anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid Tumors
Disease Type(s): Endometrial
Drug Classification(s): Targeted Therapy, Immunotherapy, Monoclonal Antibody
Molecular Target(s): PD-1, PD-L1 (CD274), PD-L2 (PDCD1LG2)
Mechanism of Action
TSR-042 is an IgG4-k humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2.
In this study, the sponsor and investigators want to learn:
- The effects of TSR-042
- How proteins that indicate the status of disease are affected with use of TSR-042
- How much TSR-042 is absorbed into the blood and how fast it is removed
- If research tests can be used in the future to predict who will benefit from TSR-042
- If the body develops proteins that work against TSR-042
- If TSR-042 prevents or delays tumor growth or shrinks an existing tumor
- Patient with histologically or cytologically proven advanced (unresectable) or metastatic solid tumor and has disease progression after treatment with available therapies that are known to confer clinical benefit or who are intolerant to treatment that meets the following requirements for the part of the study they will participate in:
- Part 1: Any advanced or metastatic solid tumor patient
- Part 2: For selected tumor types archival tumor tissue available that is formalin-fixed and paraffin-embedded or a new biopsy must be performed to obtain a tissue sample prior to study treatment initiation.
- Female patients, if of childbearing potential, must have a negative serum pregnancy test within 72 hours prior to the date of the first dose of study medication.
- Female patients of childbearing potential and male patients must agree to use 2 adequate methods of contraception with their partner starting with the screening visit through 150 days after the last dose of study therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 for Part 1 and ≤ 1 for Part 2.
- Adequate organ function.
- Patient has received prior therapy with an anti-programmed death receptor 1 (anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent.
- Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are clinically stable off steroids for at least 7 days prior to study treatment. Carcinomatous meningitis precludes a patient from study participation regardless of clinical stability.
- Known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell cancer (SqCC) of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
- Poor medical risk.
- Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study.
- Immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- Known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) (qualitative) is detected).
- Active autoimmune disease that has required systemic treatment in the past 2 years (ie, 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.
- History of interstitial lung disease.
- Patient has not recovered (ie, to ≤ Grade 1 or to baseline) from radiation- and chemotherapy-induced adverse events (AEs) or received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF) or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug.
- 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 prior to the first dose of study drug.
- Received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter. Note: palliative radiation therapy to a small field ≥ 1 week prior to Day 1 of study treatment may be allowed.
- Patient has not recovered adequately (≤ Grade 1) from AEs and/or complications from any major surgery prior to starting therapy.
- Patient has received a vaccine within 7 days of planned start of study therapy.
- Known hypersensitivity to TSR-042 components or excipients.
- Dallas, TX - Mary Crowley Cancer Research - Medical City