A Phase 1, Multiple-Dose, Dose-Escalation Trial of PT2385 Tablets, a HIF-2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma

PART 1: The primary objective of this study is to identify the maximum tolerated dose (MTD) of PT2385 Tablets and/or the recommended Phase 2 dose (RP2D) of PT2385 Tablets in patients with advanced clear cell renal cell carcinoma (ccRCC).

PART 2: The primary objective of this study is to identify the MTD of PT2385 Tablets up to the RP2D, in combination with nivolumab, in patients with advanced ccRCC.

PART 3: The primary objective of this study is to identify the MTD of PT2385 Tablets up to the RP2D, in combination with cabozantinib tablets, in patients with advanced ccRCC.

Cancer (Oncology), Cancer (Oncology) - Kidney
Song Zhao, MD, PhD
Swedish Cancer Institute
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

PART 1

  • Has locally advanced or metastatic ccRCC and has progressed during treatment with at least one prior therapeutic regimen
  • Is of age ≥ 18 years
  • Has a life expectancy of ≥ 3 months
  • Has adequate organ function
  • If a female patient, must be surgically sterile, post-menopausal, or must agree to use physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration, or if a male patient with a female partner, must agree to use physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration
  • Able to swallow oral medications

PART 2 - In addition to PART 1

  • Received no more than three prior systemic treatment regimens in the advanced or metastatic setting
  • Must have received at least one but not more than two prior anti-angiogenic therapy regimens

PART 3 - In addition to PART 1

• Must have received at least one vascular endothelial growth factor receptor (VEGFR) targeting tyrosine kinase inhibitor

Exclusion Criteria

PART 1

  • Has a history of untreated brain metastasis or history of leptomeningeal disease or spinal cord compression
  • Has failed to recover from the reversible effects of prior anticancer therapy
  • Has uncontrolled or poorly controlled hypertension
  • Is receiving warfarin anticoagulant therapy or expected to require warfarin
  • Has had any major cardiovascular event within 6 months prior to study drug administration
  • Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results
  • Has had major surgery within 4 weeks before first study drug administration
  • Has known HIV
  • Has an active infection requiring systemic treatment
  • Is participating in another therapeutic clinical trial

PART 2 - In addition to PART 1

  • Has a history of or current CNS metastases
  • Has received prior immunotherapy
  • Has any active or recent history of a known or suspected autoimmune disease

PART 3 - In addition to PART 1

  • Gastrointestinal (GI) disorders
  • Any history of congenital long QT syndrome
(206) 215-3086