First-in-human Study of CCW702 in Patients With Metastatic Castration Resistant Prostate Cancer

• ClinicalTrials.gov Identifier: NCT04077021
• Recruitment Status: Active, not recruiting
• First Posted: September 4, 2019
• Last Update Posted: October 3, 2022
• Sponsor: Calibr, a division of Scripps Research
• Information provided by (Responsible Party): Calibr, a division of Scripps Research

Tracking Information

• First Submitted Date: August 20, 2019
• First Posted Date: September 4, 2019
• Last Update Posted Date: October 3, 2022
• Actual Study Start Date: July 17, 2020
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 26, 2022)

• Part 1a and 1b: Assess the safety and tolerability of CCW702, including incidence of dose limiting toxicities [ Time Frame: up to day 28 ]
  Frequency, severity, duration of treatment-emergent and treatment-related adverse events per CTCAE v5.0
• Part 1a and 1b: Select recommended phase/part 2 dose [ Time Frame: up to 2 years ]
  Review of safety and tolerability data (adverse events, dosing) based on CTCAE v5 of all Part 1 subjects/cohorts
• Part 2: to assess clinical efficacy at the RP2D [ Time Frame: up to 2 years ]
  Responses will be measured using prostate cancer working group 3 (PCWG3) criteria

Original Primary Outcome Measures (submitted: September 3, 2019)

• Part 1, Dose escalation: to assess the safety and tolerability of increasing doses of CCW702: number of first cycle dose limiting toxicities [ Time Frame: up to 4 weeks ]
  Measure the number of first cycle dose limiting toxicities
• Part 2, Dose expansion: to assess clinical efficacy at the recommended phase 2 dose. [ Time Frame: up to 2 years ]
  Responses will be measured using prostate cancer working group 3 (PCWG3) criteria

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First-in-human Study of CCW702 in Patients With Metastatic Castration Resistant Prostate Cancer
• Official Title: A Phase 1, Open-label Study in Two Parts, Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of CCW702 in Patients With Metastatic, Castration Resistant Prostate Adenocarcinoma
• Brief Summary: CCW702 is an investigational immunotherapy for prostate cancer. This is a two-part, first-in-human study to assess the safety and tolerability of CCW702 administered subcutaneously to patients with metastatic, castration resistant prostate cancer. Part I is divided in to two subparts, in both subparts patients will receive ascending dosages of CCW702 with the goal to determine the maximum tolerated dose (MTD) of CCW702 and efficacious regimen. Part Ia will explore every other other day dosing (QOD); Part Ib will explore weekly dosing (Q7D). In part II of the study, patients will be given the recommended part/phase 2 dose (RP2D) Q7D. The study will also assess the pharmacokinetics and pharmacodynamics of CCW702.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Castration-Resistant Prostate Adenocarcinoma

Intervention

Drug: CCW702

Investigational immunotherapy for prostate cancer

Study Arms

• Experimental: Part 1a: Dose Escalation QOD
  CCW702 administered subcutaneously QOD, dose escalating cohorts.
  Intervention: Drug: CCW702
• Experimental: Part 1b: Dose Escalation Q7D
  CCW702 administered subcutaneously Q7D, dose escalating cohorts.
  Intervention: Drug: CCW702
• Experimental: Part 2: Dose Expansion
  CCW702 administered subcutaneously Q7D at RP2D.
  Intervention: Drug: CCW702

Publications *

• Kim CH, Axup JY, Lawson BR, Yun H, Tardif V, Choi SH, Zhou Q, Dubrovska A, Biroc SL, Marsden R, Pinstaff J, Smider VV, Schultz PG. Bispecific small molecule-antibody conjugate targeting prostate cancer. Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17796-801. doi: 10.1073/pnas.1316026110. Epub 2013 Oct 14.
• Lee SC, Ma JSY, Kim MS, Laborda E, Choi SH, Hampton EN, Yun H, Nunez V, Muldong MT, Wu CN, Ma W, Kulidjian AA, Kane CJ, Klyushnichenko V, Woods AK, Joseph SB, Petrassi M, Wisler J, Li J, Jamieson CAM, Schultz PG, Kim CH, Young TS. A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand. Sci Adv. 2021 Aug 11;7(33):eabi8193. doi: 10.1126/sciadv.abi8193. Print 2021 Aug.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 29, 2022): 22
• Original Estimated Enrollment (submitted: September 3, 2019): 70
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men ≥ 18 years of age at time of informed consent
• For Part 1 and Part 2: men with metastatic castration resistant prostate cancer (mCRPC) with histologically or cytologically confirmed adenocarcinoma of the prostate as defined by one or more of the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria
• Patients with treated brain metastasis or LMD are eligible if brain imaging shows no evidence of progression
• Must have prostate-specific antigen (PSA) and/or radiographic progression on AT LEAST One novel androgen receptor (AR)-targeted therapy (abiraterone acetate, enzalutamide).
• Eastern Cooperative Oncology Group performance status of 0-1
• Adequate liver function
• Adequate hematopoietic function
• Testosterone level ≤ 50 ng/mL (or 1.73 nmol/L)
• Patient has a life expectancy of greater than 12 weeks

Exclusion Criteria:

• Patients whose tumors solely exhibit neuroendocrine differentiation or small cell features by histopathology
• Patients with new or progressive brain metastasis or Leptomeningeal Disease (LMD)
• Patients with a history of clinically significant cardiovascular disease such as symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, history of stroke or myocardial infarction within 6 months of enrollment
• Patients with peripheral neuropathy CTCAE Grade >/= 2
• Patients with a known history of hypersensitivity, allergy or intolerance to CCW702 or its excipients
• Patients with untreated or imminent spinal cord compression

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04077021
• Other Study ID Numbers: CBR-CCW702-3001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Calibr, a division of Scripps Research
• Original Responsible Party: Same as current
• Current Study Sponsor: Calibr, a division of Scripps Research
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Calibr, a division of Scripps Research
• Verification Date: September 2022