Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations

NCT03570619 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: UMCC 2018.050HUM00145104
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 8

Brief Summary

This study will attempt to determine the efficacy of checkpoint inhibitor immunotherapy with nivolumab and ipilimumab combination therapy followed by nivolumab monotherapy in patients with metastatic prostate cancer and other tumor solid tumor histologies harboring loss of CDK12 function as well as monotherapy nivolumab treatment in patient with metastatic prostate cancer harboring loss of CDK12 function.

Conditions

Metastatic Castration Resistant Prostate Cancer; Metastatic Cancer; Solid Tumor

Keywords

Metastatic Cancer; Metastatic Castration Resistant Prostate Cancer; mCRPC; Immunotherapy; CDK12; Solid Tumor

Outcome Measures

Primary Outcomes (1)

• The Proportion of Patients With CDK12 Loss of Function Metastatic CRPC That Respond to Treatment.

  The primary objective is overall response rate (ORR) of patients with metastatic CRPC. Response will be defined as a 50% decline in PSA (prostate specific antigen) from baseline as determined by PCWG3 criteria.

  Up to 24 months post treatment

Secondary Outcomes (8)

• The Proportion of Patients That Respond to Treatment in Cohort B.

  Up to 104 weeks after start of therapy

• Radiographic Progression Free Survival Time (rPFS)

  Up to 104 weeks after start of therapy

• Progression Free Survival Time (PFS)

  Up to 24 months post treatment

• Duration of Therapy (DOT)

  Up to 104 weeks after start of therapy

• Progression Rate at 6 Months

  6 months

Study Arms (3)

Metastatic CRPC

EXPERIMENTAL

Patients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort A.

Drug: Nivolumab; Drug: Ipilimumab

Solid Tumors (non-prostate)

EXPERIMENTAL

Patients with all other metastatic subtypes will be enrolled in cohort B

Drug: Nivolumab; Drug: Ipilimumab

Metastatic CRPC with Monotherapy

EXPERIMENTAL

Patients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort C once enrollment to cohort A has been completed.

Drug: Nivolumab

Interventions

Nivolumab DRUG

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy. Patients in arm Metastatic CRPC will receive therapy with monotherapy nivolumab therapy at flat dose 480 mg IV every 4 weeks for up to 104 weeks of total therapy.

Metastatic CRPC; Metastatic CRPC with Monotherapy; Solid Tumors (non-prostate)

Ipilimumab DRUG

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.

Metastatic CRPC; Solid Tumors (non-prostate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥18 years of age as of date of signing informed consent.
• Be willing and able to provide written informed consent for the study.
• ECOG Performance Status of 0, 1 or 2 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.
• Subjects must have a histologic or cytologic diagnosis of metastatic adenocarcinoma of the prostate without small cell histology OR another type of metastatic carcinoma.
• All subjects, regardless of cancer type, must have a documented CDK12 aberration in tumor tissue.
• Subjects with prostate cancer must have documented prostate cancer progression within six months prior to screening with PSA progression defined as a minimum of three rising PSA levels ≥ 1; 1 week between each assessment with a baseline PSA value at screening of ≥ 2 ng/mL.
• Subjects with prostate cancer must have ongoing androgen deprivation with total serum testosterone \< 50 ng/dL (or ≤ 0.50 ng/mL or 1.73 nmol/L)). If the subject is currently being treated with LHRH agonists (subjects who have not undergone an orchiectomy), this therapy must have been initiated at least 4 weeks prior to registration. This treatment must be continued throughout the study.
• Subjects with non-prostate histologies must have RECIST 1.1-measurable cancer on computed tomography (CT) or magnetic resonance imaging (MRI) scans.
• Subjects must have recovered to baseline or ≤ grade 1 toxicities related to any prior treatments unless AE(s) are clinically non-significant and/or stable.
• Patients must be ≥ 2 weeks from most recent systemic therapy or most recent radiation therapy.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 28 days prior to registration.
• Female and male subjects of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 5 months (for women) and 7 months (for men) after the last dose of study therapy.
• Adequate organ and marrow function

You may not qualify if:

• Prior treatment with anti-PD-1/PD-L1 and anti-CTLA-4 is NOT allowed. Prior intravesical BCG therapy is allowed.
• Treatment with any investigational agent or on an interventional clinical trial within 28 days prior to registration.
• Prior or concurrent malignancy except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced prostate cancer definitively treated without recurrence or with biochemical recurrence only, or any other cancer fully treated or from which the subject has been disease-free for at least 2 years.
• Autoimmune diseases such as rheumatoid arthritis. Vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed.
• Need for systemic corticosteroids \>10mg prednisone daily or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (such as cyclosporine or methotrexate) Topical and inhaled corticosteroids are allowed if medically needed.
• Any history of organ allografts
• Any history of HIV, hepatitis B or hepatitis C infection

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Memorial Sloan Kettering Cancer Center: collaborator
• University of California, San Francisco: collaborator

Study Sites (8)

University of California San Diego, Moores Cancer Center

San Diego, California, 92093, United States

Location

University of California San Francisco/Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

H. Lee. Moffitt Cancer Center & Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: University of Michigan Cancer Center Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

7349369499

Study Officials

• Ajjai Alva, MD

  Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: June 27, 2018
• Study Start: December 14, 2018
• Primary Completion: December 22, 2022
• Study Completion: March 26, 2024
• Last Updated: May 8, 2025
• Results First Posted: January 30, 2024

Record last verified: 2025-04

Locations

US (8)