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Clinical Trials/NCT03888612
NCT03888612CompletedPhase 1

A Phase 1/2, Open-label, Dose Escalation, and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARV-110 in Patients With Metastatic Castration Resistant Prostate Cancer

Arvinas Androgen Receptor, Inc.1 site in 1 country248 target enrollmentStarted: March 1, 2019Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 1
Status
Completed
Enrollment
248
Locations
1
Primary Endpoint
Part A: Incidence of Dose Limiting Toxicities of ARV-110

Study Overview

Brief Summary

Phase 1/2 dose escalation study to assess the safety and tolerability of ARV-110 in men with mCRPC who have progressed on prior approved systemic therapies for their castrate resistant disease (one of which must be enzalutamide or abiraterone).

Study Design

Study Type
Interventional
Allocation
Na
Intervention Model
Single Group
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
18 Years to — (Adult, Older Adult)
Sex
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Patients must be male and at least 18 years of age at the time of signing the informed consent.
  • Patients must present with histological, pathological, or cytological confirmed diagnosis of advanced or metastatic castration resistant adenocarcinoma of the prostate.
  • Patients must have progressed on at least 2 prior approved systemic therapies for CRPC (at least one must be abiraterone or enzalutamide).
  • Patients with progressive mCRPC
  • Patients must have ongoing ADT with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration).
  • Patients must be male and at least 18 years of age at the time of signing the informed consent.
  • Patients must present with histological, pathological, or cytological confirmed diagnosis of advanced or metastatic castration resistant adenocarcinoma of the prostate.
  • Patients must have received at least one but no more than two prior second generation anti-androgen agents (e.g., enzalutamide or abiraterone) for CRPC.
  • Patients must have received no more than one prior chemotherapy regimen in each of the following settings: castrate sensitive and castrate resistant prostate cancer.
  • Patients must have ongoing ADT with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration).
  • Part B - Phase 2 Expansion Cohort Subgroup 4
  • Patient has received only one prior AR second generation therapy (e.g., abiraterone or enzalutamide) either as treatment for CSPC or CRPC and no more than 1 regimen in CRPC setting.
  • No prior chemotherapy

Exclusion Criteria

  • Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses)
  • Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug.
  • Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study
  • Systemic anti cancer therapy within 2 weeks of first dose of study drug (6 weeks for bicalutamide, mitomycin C, or nitrosoureas and 4 weeks for abiraterone). Patients are ineligible if they received any other type of anti cancer agent (except agents to maintain castrate status) within 2 weeks before first dose of study drug.
  • Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses)
  • Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug.
  • Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study
  • Systemic anti cancer therapy within 2 weeks of first dose of study drug (6 weeks for bicalutamide, mitomycin C, or nitrosoureas and 4 weeks for abiraterone). Patients are ineligible if they received any other type of anti cancer agent (except agents to maintain castrate status) within 2 weeks before first dose of study drug.

Arms & Interventions

ARV-110

Experimental

Part A: Oral tablet(s), once or twice daily in 28 day cycles

Part B: Oral tablet(s), once or twice daily in 28 day cycles

Intervention: ARV-110 (Drug)

Outcomes

Primary Outcomes

Part A: Incidence of Dose Limiting Toxicities of ARV-110

Time Frame: 28 Days

First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug

Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-110

Time Frame: 28 Days

Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.

Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-110

Time Frame: 28 Days

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Part B: Measurement of PSA response rate per PCWG3 accessing anti-tumor activity of ARV-110

Time Frame: 12 Weeks

PSA response rate per PCWG3.

Part B: Measurement of overall RECIST response rate accessing the anti-tumor activity of ARV-110

Time Frame: 12 Weeks

Overall RECIST response rate in patients with measurable disease at baseline.

Part B: To evaluate the clinical anti-tumor activity of ARV-110 in patients with mCRPC

Time Frame: 12 Weeks

To evaluate the clinical anti-tumor activity (PSA response rate per PCWG3, Overall RECIST RR, rPFS, and PFS) of ARV-110 in patients with mCRPC in different subgroups of patients with mCRPC with predefined tumor genomic and molecular profiles or based on prior therapy.

Secondary Outcomes

  • Part A: Anti-tumor activity based on the overall PSA response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
  • Part A: Anti-tumor activity based on the overall RECIST response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
  • Part A: Anti-tumor activity based on the progression free survival in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
  • Part A: Anti-tumor activity based on the overall survival in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
  • Part A: Anti-tumor activity based on the duration of response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
  • Part A: Concentration-time curve (AUC) for single and multiple dose of ARV-110(28 Days)
  • Part A: Anti-tumor activity based on the time to progression in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.(12 Weeks)
  • Part A: Maximum concentration (Cmax) for single and multiple dose of ARV-110(28 Days)
  • Part A: Minimum concentration (Cmin) for single and multiple dose of ARV-110(28 Days)
  • Part A: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110(28 Days)
  • Part B: Concentration-time curve (AUC) for single and multiple dose of ARV-110(28 Days)
  • Part B: Maximum concentration (Cmax) for single and multiple dose of ARV-110(28 Days)
  • Part B: Minimum concentration (Cmin) for single and multiple dose of ARV-110(28 Days)
  • Part B: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110(28 Days)
  • Part B: Duration of response(12 Weeks)
  • Part B: Overall survival(12 Weeks)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (1)

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