Clinical trial NCT04077021: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Castration-Resistant Prostate Adenocarcinoma
Lead sponsor: Calibr, a division of Scripps Research
Sponsor class: OTHER
First posted: 2019-09-04
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Part 1a and 1b: Assess the safety and tolerability of CCW702, including incidence of dose limiting toxicities
timeFrame: up to day 28
measure: Part 1a and 1b: Select recommended phase/part 2 dose
timeFrame: up to 2 years
measure: Part 2: to assess clinical efficacy at the RP2D
timeFrame: up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University - Sydney Kimmel Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References:
citation: 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.
citation: 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.