DS3201 and Ipilimumab for the Treatment of Metastatic Prostate, Urothelial and Renal Cell Cancers

NCT04388852 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2019-0967NCI-2020-02916
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the side effects and best dose of DS3201 when given together with and ipilimumab for the treatment of patients with prostate, urothelial, or renal cell cancer that has spread to other places in the body (metastatic). DS3201 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving DS3201 and ipilimumab may help to control the disease.

Conditions

Metastatic Urothelial Carcinoma; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Aggressive Variant Prostate Carcinoma; Castration-Resistant Prostate Carcinoma; Metastatic Clear Cell Renal Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Prostate Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Adverse events will be graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 and tabulated by grade and ETOX status. All adverse events will be presented descriptively by event, grade, and attribution separately by dose level.

  Up to 60 days after last valemetostat dose and 100 days after last ipilimumab dose

• Maximum tolerated dose

  Up to 21 days

Secondary Outcomes (3)

• Immunologic and molecular effects

  Up to 2 years

• Time to treatment failure (TTF)

  Up to 2 years

• Overall response rate (ORR)

  Up to 2 years

Study Arms (1)

Treatment (valemetostat, ipilimumab)

EXPERIMENTAL

Patients receive valemetostat PO QD on days 1-21 and ipilimumab IV over 90 minutes on day 1 of cycles 1 and 3. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Drug: Valemetostat

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Treatment (valemetostat, ipilimumab)

Valemetostat DRUG

Given PO

Also known as: DS 3201, DS-3201, DS3201

Treatment (valemetostat, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Histologically or cytologically confirmed prostate carcinomas, urothelial carcinomas and clear cell renal carcinomas. For patients with prostate carcinomas, variant histologies, such as small cell or neuroendocrine carcinomas are permitted
• Evidence of metastatic disease by conventional imaging studies (computed tomography \[CT\], magnetic resonance imaging \[MRI\] and/or bone scan). Patients with locally advanced disease that is not amenable to locoregional therapies such as surgery or radiation, are considered metastatic and eligible to participate
• Patients with prostate carcinomas must have castration resistant disease, i.e. evidence of disease progression while having castrate levels of testosterone (=\< 50 ng/dL or =\< 2.0 nM) or an unsatisfactory response to \>= 1 month of castration, as defined by lack of symptom control and/or serum tumor marker response of \< 20% (confirmed by a second value drawn on a different day). Exception: patients with small cell carcinoma histology are not required to have progressed during prior androgen deprivation therapy. However, all patients with prostate cancer (including those with small cell carcinomas) are required to maintain castrate levels of testosterone throughout the duration of the study
• Patients with prostate carcinomas must also display the AVPC molecular signature (i.e. known loss or mutation \[by Clinical Laboratory Improvement Act (CLIA) certified molecular testing by immunohistochemistry (IHC) and/or deoxyribonucleic acid (DNA) sequencing in solid tumor samples, and/or in circulating tumor DNA\]) in at least 2 of the following: Tp53, RB1 and PTEN
• Patients with renal cell carcinomas (RCC) must have had progressive disease during or after treatment with at least one anti-angiogenic agent and one PD-1 or PD-L1 inhibitor
• Patients with urothelial carcinomas (UC) must have had progressive disease during or after treatment with at least one anti-PD1 or PD-L1 inhibitor and must have previously been treated with platinum-based chemotherapy or not be eligible for platinum based chemotherapy
• Patients with AVPC are allowed to have received prior treatment with a PD-1 or PD-L1 inhibitor, but are not required to have had it
• Evidence of disease progression as defined by new or increasing measurable and/or non-measurable disease as per RECIST
• For patients with AVPC, rising PSA values (a minimum of 2 rising values over 3 measurements obtained a minimum of 7 days apart with the last result being \>= 1.0 ng/mL, as per Prostate Cancer Working Group 3 \[PCWG3\]) can also be considered evidence of progressive disease for eligibility as long as the molecular AVPC criteria are also met
• If patient has known brain metastases, must have stable neurologic status following local therapy for at least 4 weeks without the use of steroids or on stable or decreasing dose of =\< 10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)
• Recovery from recent surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or =\< grade 1 (other than alopecia). Other low grade toxicities (e.g. =\< grade 2 lymphopenia or hypomagnesemia) may be allowed at the discretion of the investigator if considered clinically insignificant
• Absolute neutrophil count (ANC) \>= 1,500/uL (obtained within 28 days prior to day 1 of treatment)
• Platelet count \>= 100,000/uL (obtained within 28 days prior to day 1 of treatment)
• Hemoglobin (Hgb) \>= 9 g/dL (obtained within 28 days prior to day 1 of treatment)

You may not qualify if:

• Pregnant or lactating
• Carcinomatous meningitis
• Prior treatment with an EZH2 inhibitor
• PD-1, PD-L1, PD-L2 or CTLA-4 inhibitor (whether commercially available or investigational) within 4 weeks prior to day 1 of treatment
• Monoclonal antibody (whether commercially available or investigational) within 4 weeks prior to day 1 of treatment
• Investigational drug within 2 weeks prior to day 1 of study treatment
• Chemotherapy within 2 weeks prior to day 1 of study treatment
• Radiation therapy or radionuclide therapy within 2 weeks prior to day 1 of study treatment
• Receipt of live virus vaccination within 30 days prior to day 1 of study treatment
• Untreated symptomatic spinal cord compressions or brain metastases
• Experienced an immune-related adverse event (irAE) that led to permanent discontinuation of prior immunotherapy
• Experienced a \>= grade 3 irAE within the past 16 weeks, any grade 4 life- threatening irAE (regardless of duration) or neurologic or ocular AE of any grade while receiving prior immunotherapy (NOTE: Patients with endocrine AEs of any grade are permitted to enroll if they are stably maintained on appropriate replacement therapy, but must have no history of adrenal crisis and be asymptomatic)
• Active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis or eczema not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Requires chronic systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications. Inhaled, intranasal, intra-articular and topical (including ocular) steroids are allowed. Adrenal replacement (i.e., physiologic replacement) doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• History of interstitial lung disease, idiopathic pulmonary fibrosis or evidence of active pneumonitis on screening chest computed tomography (CT) scan

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; Neoplasm Metastasis; Prostatic Neoplasms; Carcinoma, Transitional Cell; Carcinoma, Renal Cell

Interventions

Ipilimumab; CTLA-4 Antigen

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases; Urologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Ana Aparicio

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 14, 2020
• Study Start: August 20, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)