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

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration-Resistant Prostate Adenocarcinoma
• Intervention / Treatment: Drug: CCW702

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92093
      • University of California at San Diego
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University - Sydney Kimmel Comprehensive Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1a: Dose Escalation QOD; CCW702 administered subcutaneously QOD, dose escalating cohorts.	Drug: CCW702; Investigational immunotherapy for prostate cancer
Experimental: Part 1b: Dose Escalation Q7D; CCW702 administered subcutaneously Q7D, dose escalating cohorts.	Drug: CCW702; Investigational immunotherapy for prostate cancer
Experimental: Part 2: Dose Expansion; CCW702 administered subcutaneously Q7D at RP2D.	Drug: CCW702; Investigational immunotherapy for prostate cancer

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Calibr, a division of Scripps Research

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2020
• Primary Completion (Actual): October 21, 2022
• Study Completion (Actual): October 21, 2022

Study Registration Dates

• First Submitted: August 20, 2019
• First Submitted That Met QC Criteria: September 3, 2019
• First Posted (Actual): September 4, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Adenocarcinoma
• Other Study ID Numbers: CBR-CCW702-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No