Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Behaviors and Mental Disorders

Nervous System Diseases

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Prostatic Neoplasms

Carcinoma, Renal Cell

Aggression

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Transitional Cell Carcinoma

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Valemetostat

Ana Aparicio

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.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and confirm the safety and tolerability of valemetostat (DS3201) given in combination with ipilimumab in patients with metastatic aggressive variant prostate cancers (AVPC), urothelial carcinomas (UC) and renal clear cell carcinomas (RCC).

II. To screen for associations between changes in the tumor microenvironment and clinical outcomes.

SECONDARY OBJECTIVES:

I. To assess the immunologic and molecular effects on tissue samples of participants treated with DS3201 in combination with ipilimumab in patients with metastatic AVPC, UC and RCC.

II. To estimate the time to treatment failure (TTF) of patients with metastatic AVPC, UC and RCC treated with DS3201 in combination with ipilimumab.

III. To estimate the overall response rate (ORR) of patients with metastatic AVPC, UC and RCC treated with DS3201 in combination with ipilimumab (in patients with AVPC ORR will be reported separately for prostate specific antigen \[PSA\], circulating tumor cells \[CTC\] and measurable and non-measurable disease by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1).

OUTLINE: This is a dose-escalation study of valemetostat.

Patients receive valemetostat orally (PO) once daily (QD) on days 1-21 and ipilimumab intravenously (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.

After completion of study treatment, patients are followed up 30 and 60 days after the last valemetostat dose and/or 100 days after the last ipilimumab dose and then every 6 months thereafter.

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

DS3201 With Ipilimumab in Patients With Metastatic Aggressive Variant Prostate (AVPC), Urothelial (UC), and Renal Cell (RCC) Carcinomas

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.

Descriptive statistics including plots, mean, median and standard deviations will be used to summarize data by dose level and patient disease cohort. Tumor immune cell infiltration and peripheral blood immune populations will be described and graphed over time. Differences in either time point compared to baseline will be compared with a t-test or non-parametric alternative. Cox models will be implemented to explore the relationship of treatment combination, tumor immune infiltration/peripheral blood immune subpopulations, and time to treatment failure.

Defined as the time interval between the first day of treatment with DS3201 and treatment failure. Median TTF will be reported with a 95% confidence interval using Kaplan-Meier methods. If the median is not reached, then the TTF estimate will be reported with the standard error at a time close to the median follow-up time. The full TTF experience will be presented with a Kaplan-Meier plot overall and by disease cohort.

In patients with renal cell carcinoma and urothelial carcinoma, ORR is defined as the rate of confirmed complete responses + partial responses as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and as assessed by the investigator. In patients with aggressive variant prostate cancer, ORR will be reported separately for prostate specific antigen (\>= 50% decline from baseline value), CTC (conversion from unfavorable to favorable counts) and measurable and non-measurable disease (per RECIST 1.1) and as assessed by the investigator. ORR will be reported with a 95% Blythe-Still-Casella exact confidence interval.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Digestive System Diseases

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Bevacizumab

Atezolizumab

Angiogenesis Inhibitors

Growth Inhibitors

In Phase 1b patients will receive valemetostat (DS-3201) orally daily at their assigned dose level, plus atezolizumab 1200 mg intravenously (IV) on day 1, and bevacizumab 15 mg/kg IV on day 1 of each cycle.

During Phase 1b, a 3+3 dose escalation design will be utilized to define the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) with starting dose of valemetostat 150mg by mouth daily.

During Phase II, study participants will receive valemetostat (DS-3201) orally daily at MTD/RP2D, plus atezolizumab 1200 mg intravenously (IV) on day 1, and bevacizumab 15 mg/kg IV on day 1 of each cycle.

Valemetostat is an inhibitor of the enzymes enhancer of zeste homolog 1 (EZH1) and enhancer of zeste homolog 2 (EZH2).

Atezolizumab is commercially available. Atezolizumab combined with bevacizumab is approved for frontline treatment of advanced HCC based on IMbrave150 clinical trial. It will be administered as per the package insert and institutional standards.

Bevacizumab is commercially available. Bevacizumab combined with atezolizumab is approved for frontline treatment of advanced HCC based on IMbrave150 clinical trial. It will be administered as per the package insert and institutional standards.

Margaret Thomas, MPH

Pamela M Hardwick

Mehmet S Akce, MD

This is a phase Ib/II, dose escalation and dose expansion study of valemetostat (DS-3201) with atezolizumab and bevacizumab in patients advanced Hepatocellular carcinoma (HCC) who did not receive prior systemic therapy for advanced HCC.

Patients will be started on valemetostat (DS-3201) with atezolizumab and bevacizumab, restaging scans will be performed every 9 weeks. The treatment will be continued until progressive disease (PD), unacceptable toxicity or consent withdrawal. Paired research biopsies will be performed.

This study will enroll up to approximately 45-patients at UAB. It is estimated 2 patients will be enrolled per month over up to 36 months period.

Patients will receive valemetostat (DS-3201) orally daily at their assigned dose level, plus atezolizumab 1200 mg intravenously (IV) on day 1, and bevacizumab 15 mg/kg IV on day 1 of each cycle. Each cycle is 21 days. Atezolizumab and bevacizumab will be administered based on institutional guidelines and practice at the FDA approved dosages and intervals for advanced HCC. Valemetostat should be taken immediately prior to the start of atezolizumab and bevacizumab infusion on day 1 of each cycle.

A Study of Valemetostat Tosylate (DS-3201b) With Atezolizumab and Bevacizumab in HCC

A Phase Ib/II, Dose Escalation and Dose Expansion Study of Valemetostat Tosylate (DS-3201b) With Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma (HCC)

Evaluate the safety, tolerability, and MTD/RP2D of valemetostat when administered with atezolizumab and bevacizumab in advanced HCC (phase 1b).

Estimate the objective response rate (ORR) by RECIST version 1.1. per investigator assessment for valemetostat when administered with atezolizumab and bevacizumab at RP2D in advanced HCC (phase II).

Evaluate the safety and pharmacokinetic (PK) profile of valemetostat in combination with atezolizumab and bevacizumab.

Estimate progression free survival (PFS) for valemetostat when administered with atezolizumab and bevacizumab in advanced HCC.

Estimate overall survival (OS) for valemetostat when administered with atezolizumab and bevacizumab in advanced HCC.

Estimate duration of response (DoR) for valemetostat when administered with atezolizumab and bevacizumab in advanced HCC.

Estimate the disease control rate (DCR) for valemetostat when administered with atezolizumab and bevacizumab in advanced HCC.

University of Alabama at Birmingham

Associate Professor

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, Follicular

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

Antirheumatic Agents

Rituximab

Lenalidomide

Immunologic Factors

The dose escalation phase will assess the safety/tolerability of escalating doses of valemetostat and lenalidomide when combined with rituximab

Loretta Nastoupil, MD

To find a recommended dose of valemetostat that can be given in combination with rituximab and lenalidomide to patients with follicular lymphoma. The safety and effects of this drug combination will also be studied

Primary Objectives: Phase 1

--Evaluate the safety and tolerability of valemetostat in combination with R2 in subjects with R/R FL and determine the recommended phase 2 dose (RP2D) for evaluation in phase 2.

Secondary Objectives: Phase 1

* Evaluate the efficacy of valemetostat in combination with R2 in R/R FL
* Evaluate the pharmacokinetics (PK) of valemetostat in combination with R2

Exploratory Objective: Phase 1

* Evaluate pharmacodynamic profile of valemetostat
* Evaluate the efficacy of valemetostat in combination with R2 in R/R FL

Primary Objective: Phase 2

--Evaluate the efficacy of valemetostat in combination with R2 in R/R FL

Secondary Objective: Phase 2

* Evaluate the ORR
* Evaluate the DOR
* Evaluate the time to next anti-lymphoma treatment (TTNT)
* Evaluate the safety and tolerability
* Evaluate the PK of valemetostat in combination with R2

Exploratory Objective: Phase 2

* Evaluate the PFS of valemetostat in combination with R2 in R/R FL
* Evaluate OS
* Evaluate the effect of valemetostat in combination with R2 in R/R FL on epigenetic remodeling and gene expression
* Evaluate changes in tumor/immune microenvironment
* Evaluate pharmacodynamic profile of valemetostat

A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma

Daiichi Sankyo

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Trastuzumab

Trastuzumab deruxtecan

Immunoconjugates

Participants will receive the same drugs at the same schedule, and the same dose of trastuzumab deruxtecan

Participants will only receive 1 dose level of valemetostat.

Senthil Damodaran, MD, PHD

Senthil, MD, PHD

To find a recommended dose of valemetostat that can be given in combination with trastuzumab deruxtecan to patients with low/ultra-low HER2-expressing metastatic breast cancer.

Primary Objectives:

Dose escalation part:

1. To evaluate the safety and determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) of valemetostat in combination with trastuzumab deruxtecan (T-DXd).

   Dose expansion part:
2. To evaluate the objective response rate (ORR) of valemetostat at the RDE in combination with T-DXd.

Secondary Objectives:

Dose escalation:

1. To determine ORR; defined as a percentage of subjects who achieve complete response (CR) or partial response (PR) by RECIST 1.1 criteria.
2. To determine survival outcomes, including duration of response (DoR), progression free survival (PFS), and overall survival (OS).
3. To determine the Clinical Benefit Rate (CBR) defined as stable disease (SD) ≥ 16 weeks + PR + CR.

Dose expansion:

1. To determine survival outcomes, including DoR, PFS, and OS.

   * DOR of the proposed treatment: the time from observing response to the valemetostat treatment until objective tumor progression (PD)
   * PFS: the time from starting valemetostat treatment until objective tumor progression (PD) or death due to any cause.
   * Overall survival (OS): the time from starting valemetostat treatment until death due to any cause.
2. To determine the CBR defined as SD ≥16 weeks + PR + CR.
3. To evaluate safety of valemetostat in combination with T-DXd.
4. To evaluate the pharmacokinetics (PK) of both the drugs in combination.
5. To evaluate the immunogenicity of T-DXd

Exploratory Objectives:

1. To investigate pharmacodynamic biomarkers.
2. To investigate biomarkers that may aid in identifying subjects who may derive clinical benefit.

Phase 1b Study of EZH1/2 Inhibitor Valemetostat in Combination With Trastuzumab Deruxtecan in Subjects With HER2 Low/Ultra-low/Null Metastatic Breast Cancer

Obinutuzumab

CC-99282

Tafasitamab

BMS Study Connect Contact Center http://www.bmsstudyconnect.com

First line of the email MUST contain the NCT# and Site #.

Javier Munoz, Site 109

Site 114

Muhamad Alhaj Moustafa, Site 111

Julio Chavez, Site 102

Marc Hoffmann, Site 108

Grzegorz Nowakowski, Site 107

Loretta Nastoupil, Site 101

Maria Clavijo, Site 255

Site 254

Site 253

Mariza Schaan, Site 453

Guilherme Fleury Perini, Site 450

Eduardo Magalhaes Rego, Site 451

Site 452

John Kuruvilla, Site 201

Alejandro Berkovits, Site 354

Sergio Portiño, Site 355

Raimundo Gazitua, Site 353

Site 352

Marcelo Garrido, Site 350

Hongmei Jing, Site 653

Wenyu Li, Site 657

Keshu Zhou, Site 655

Huijing Wu, Site 660

Xiaojing Yan, Site 662

Wei Yang, Site 663

Site 650

Lihua Qiu, Site 651

Huiqiang Huang, Site 659

Judit Meszaros Joergensen, Site 602

Site 601

Site 603

Fontanet Bijou, Site 407

Corinne Haioun, Site 403

Franck Morschhauser, Site 406

Guillaume Cartron, Site 409

Catherine Thieblemont, Site 405

Emmanuel Bachy, Site 402

Fabrice JARDIN, Site 404

Pierre Bories, Site 408

Vincent Ribrag, Site 401

Site 150

Site 151

Abraham Avigdor, Site 152

Alessandro Rambaldi, Site 501

Vittorio Stefoni, Site 504

Site 503

Site 502

Site 506

Won-Sik Lee, Site 553

Sung-Soo Yoon, Site 551

Won-Seog Kim, Site 550

Seok-Goo Cho, Site 552

Site 306

Cecilia Carpio Segura, Site 301

Raul Cordoba, Site 302

Site 304

Antonio Rueda-Domínguez, Site 303

Site 305

Victoria Campbell, Site 802

Andrew Davies, Site 803

Bristol-Myers Squibb

The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of CC-99282 alone and in combination with anti-lymphoma agents in participants with relapsed or refractory non-Hodgkin's lymphomas.

Participants with relapsed or refractory non-Hodgkin's lymphomas (R/R NHL) who have failed at least 2 lines of therapy (or have received at least one prior line of standard therapy and are not eligible for any other therapy).

The dose escalation will evaluate the safety and tolerability of escalating doses of CC-99282 in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) and/or relapsed or refractory follicular lymphoma (R/R FL) participants to determine the maximum tolerated dose (MTD) of CC-99282 as monotherapy.

The dose expansion will further evaluate the safety and preliminary efficacy of single agent CC-99282 or the safety and preliminary efficacy of CC-99282 in combination with anti-lymphoma agents in participants with R/R DLBCL and NHL.

Part B Cohort B will further evaluate the potential effects of food on the PK and safety of CC-99282.

A Safety and Preliminary Efficacy Study of CC-99282, Alone and in Combination With Anti-lymphoma Agents in Participants With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL)

A Phase 1/2, Multi-center, Open-label Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of an Orally Available Small Molecule, CC-99282, Alone and in Combination With Anti-Lymphoma Agents in Subjects With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL).

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Defined as the percent of subjects whose best response is Complete Response (CR) or Partial Response (PR).

Determined by the Lugano Classification for NHL response criteria

Determined by the Lugano Classification for NHL response criteria

Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause

Determined by the Lugano Classification for NHL response criteria

Time from first dose of CC-99282 to death from any cause

Determined by the Lugano Classification for NHL response criteria

Defined as the percent of subjects whose best response is Complete Response (CR) or Partial Response (PR).

Determined using the modified International PCNSL Collaborative Group (IPCG) criteria

Determined using the modified International PCNSL Collaborative Group (IPCG) criteria

Celgene

Respiratory Tract (Lung and Bronchial) Diseases

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
DS3201 and Ipilimumab for the Treatment of Metastatic Prostate, Urothelial and Renal Cell Cancers	NCT04388852	Aggressive Vari... Castration-Resi... Metastatic Clea... Metastatic Mali... Metastatic Pros... Metastatic Urot... Stage IV Prosta... Stage IV Renal ... Stage IVA Prost... Stage IVB Prost...	Ipilimumab Valemetostat	18 Years -	M.D. Anderson Cancer Center
A Study of Valemetostat Tosylate (DS-3201b) With Atezolizumab and Bevacizumab in HCC	NCT06294548	Hepatocellular ...	Valemetostat Atezolizumab Bevacizumab	18 Years -	University of Alabama at Birmingham
A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma	NCT05683171	Lymphoma	Rituximab Lenalidomide Valemetostat	18 Years -	M.D. Anderson Cancer Center
Phase 1b Study of EZH1/2 Inhibitor Valemetostat in Combination With Trastuzumab Deruxtecan in Subjects With HER2 Low/Ultra-low/Null Metastatic Breast Cancer	NCT05633979	Breast Cancer	Trastuzumab der... Valemetostat	18 Years -	M.D. Anderson Cancer Center
A Safety and Preliminary Efficacy Study of CC-99282, Alone and in Combination With Anti-lymphoma Agents in Participants With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL)	NCT03930953	Lymphoma, Non-H...	CC-99282 Rituximab Obinutuzumab Tafasitamab Valemetostat	18 Years -	Celgene
Phase 1b Study of EZH1/2 Inhibitor Valemetostat in Combination With Trastuzumab Deruxtecan in Subjects With HER2 Low/Ultra-low/Null Metastatic Breast Cancer	NCT05633979	Breast Cancer	Trastuzumab der... Valemetostat	18 Years -	M.D. Anderson Cancer Center
A Study of Valemetostat Tosylate (DS-3201b) With Atezolizumab and Bevacizumab in HCC	NCT06294548	Hepatocellular ...	Valemetostat Atezolizumab Bevacizumab	18 Years -	University of Alabama at Birmingham
Study of Front Line Pembrolizumab and Valemetostat in PD-L1 Positive, HPV-Negative Recurrent/Metastatic Squamous Cell Carcinoma (SCC) of the Head and Neck: The PANTHERAS	NCT05879484	Sinonasal Cance... Squamous Non-sm... Lung Cancer Head and Neck S... Head and Neck C... Head and Neck C...	pembrolizumab valemetostat	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for valemetostat

Every month we try and update this database with for valemetostat cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.