Clinical Trial 19186

Cancer Type: Gynecological Tumor
Interventions:Not Applicable; TSR-042

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Hye Sook Chon

Overview

Study Title

A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid Tumors

Summary

The purpose of this study is to evaluate the ability of a new drug, TSR-042, to reduce the size of tumors in study participants who have advanced tumors.

Objective

Primary Objectives: Part 1 - Dose Escalation Cohorts: - To evaluate the safety and tolerability of TSR-042 in patients with advanced solid tumors and determine the recommended Phase 2 dose (RP2D) and schedule. Part 2A - Fixed-Dose Safety Evaluation Cohorts: - To evaluate the safety and tolerability of TSR-042 at fixed-dose in patients with advanced solid tumors and determine the RP2D and schedule. Part 2B - Expansion Cohorts: - Cohorts A1 and A2: To evaluate the antitumor activity of TSR-042 in patients with recurrent and advanced endometrial cancer, in terms of objective response rate (ORR) and duration of response (DOR) by independent blinded central review using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - Cohorts B, C, D, and E: To evaluate the antitumor activity of TSR-042 in patients with advanced solid tumors, in terms of immune-related objective response rate (irORR) by Investigators' assessment using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Secondary Objectives: Part 1 - Dose Escalation Cohorts: - To evaluate irORR as assessed by the Investigators using irRECIST. Part 1 and Part 2: - To characterize the pharmacokinetic (PK) profile of TSR-042. - To characterize the pharmacodynamic (PDy) profile of TSR-042. - To evaluate the immunogenicity of TSR-042. - To evaluate additional measures of clinical benefit, including: - Immune-related disease control rate (irDCR) based on Investigators' assessment using.irRECIST. - Immune-related duration of response (irDOR) based on Investigators' assessment using irRECIST. - Immune-related progression-free survival (irPFS) based on Investigators' assessment using irRECIST. - Progression-free survival (PFS) based on independent blinded central review using RECIST v1.1 in endometrial cancer cohorts (Cohorts A1 and A2). - Immune-related overall response rate (irORR) based on Investigators' assessment using irRECIST (Cohorts A1 and A2). - Disease control rate (DCR) based on Investigators' assessment using RECIST v1.1 (Cohorts A1 and A2). - Overall survival (OS). Exploratory Objectives: - To explore changes in intratumoral cells and circulating biomarkers in the blood following treatment with TSR-042. - To explore the profile of tumor-infiltrating lymphocytes (TILs), tumor cell characteristics, and/or circulating biomarkers prior to treatment with TSR-042 and correlate with clinical benefit.

Inclusion Criteria

  • Age 18 years or older
  • Have MSI-High or MSS endometrial cancer (except endometrial sarcoma) that has progressed on or after 1 or 2 previous lines of chemotherapy for advanced or metastatic disease. Past treatment with hormone therapies does not count towards the number of lines of therapy noted. Must have at least one measurable lesion on my baseline MRI/CT scan.
  • Female participants must either have a negative pregnancy test within 72 hours before the first dose of study medication OR be of non-childbearing potential. > Females of childbearing potential 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.
  • Adequate organ function.
  • Additional criteria may apply.

  • Exclusion Criteria

  • 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.
  • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  • Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid (HCV RNA) (qualitative) is detected).
  • 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 (e.g., 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.
  • Pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of study treatment.
  • Additional criteria may apply.