Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tyrosine Kinase Inhibitors

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

Monotherapy: OTX-2002 (Cycle length = 4 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks

OTX-2002 + Tyrosine Kinase Inhibitor One: (Cycle length = 4 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks.

Tyrosine Kinase Inhibitor One will be standard per the respective fixed local approved dose

OTX-2002 + Tyrosine Kinase Inhibitor Two : (Cycle length = 4 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks.

Tyrosine Kinase Inhibitor Two will be standard per the respective fixed local approved dose

OTX-2002 + Immune Checkpoint Blockade: (Cycle length = 6 weeks) OTX-2002 will be administered as an IV infusion over 80-120 minutes every 2 weeks.

Checkpoint Inhibitor will be standard per the respective fixed local approved dose

OTX-2002 is a lipid nanoparticle (LNP) that contains a biscistronic mRNA that codes for 2 independent epigenomic controllers.

OTX-2002

Tyrosine kinase inhibitor One

Tyrosine kinase inhibitor Two

monoclonal antibody that binds to PD-1 or PD-L1

Checkpoint Inhibitor, Immune

Head of Clinical Development Operations

Chief Medical Officer

Daneng Li

Taryn King

Aurelie Desgardin

Hang Chang

Sharon Jerdonek

Susanna V Ulahannan

Cynthia DeLeon

GI Nurse Navigator

Stephen Lam Cham

Thomas Chung Cheung Yau

Min-hee Ryu

Tae-Yong Kim

Choong-Kun Lee

David Tai Wai-Meng

Yong Wei Peng

Chia-Jui Yen

Chia-Chi Lin

Yan Moore, MD

This is a Phase 1/2 open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as a single agent and in combination with standard of care in patients with hepatocellular carcinoma (HCC) and other solid tumor types known for association with the MYC oncogene.

The study consists of Part 1 (OTX-2002 monotherapy) and Part 2 (OTX-2002 combined with standard of care in hepatocellular carcinoma). Part 1 consists of escalation and expansion, and Part 2 consists of safety run-in and expansion. The objective of Part 1 escalation and Part 2 safety run-in will be safety and tolerability, while anti-tumor activity will be evaluated as the primary endpoint in Part 1 and Part 2 expansion.

This is a Phase 1/2 open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as a single agent and in combination with standard of care in patients with hepatocellular carcinoma (HCC) and other solid tumor types known for association with the MYC oncogene. The study consists of Part 1 (OTX-2002 monotherapy) and Part 2 (OTX-2002 combined with standard of care in hepatocellular carcinoma).

In Part 1, during dose escalation, participants with HCC and other solid tumors that progressed on, relapsed after, are refractory to, or are intolerant of standard of care for which no treatment options are available will be administered an intravenous infusion of OTX-2002 as a single agent. The escalation will be conducted using a 3+3 design, with the primary endpoint of dose limiting toxicity (DLT), maximum tolerated dose (MTD), and incidence of treatment emergent adverse events (TEAEs). In Part 1 expansion, 15-25 participants with BCLC stage B or C, Child-Pugh Class A HCC who have received at least 1 prior line of systemic anticancer treatment, and without available subsequent standard of care, will receive OTX-2002 at the recommended dose for expansion (RDE) for monotherapy. The primary endpoint of Part 1 expansion will be overall response rate (ORR) and duration of response (DoR).

In Part 2, during safety run-in, participants with BCLC stage B or C, Child-Pugh Class A HCC who have received at least 1 prior line of systemic anticancer treatment, and without available subsequent standard of care, will receive OTX-2002 at the selected dose in combination with standard of care therapies at the local approved dose. The primary endpoint of Part 2 safety run-in will be DLT, MTD, and incidence of TEAE. Once the combination therapies have been determined to be tolerable in the safety run-in, 15-25 HCC participants will be enrolled in Part 2 expansion for each of the combination therapies. The primary endpoint of Part 2 expansion will be ORR and DoR.

Part 1 OTX-2002 monotherapy dose escalation and expansion in participants with hepatocellular carcinoma (HCC) and other solid tumors

During the monotherapy dose escalation phase, participants will be enrolled in sequential cohorts of increasing doses of OTX-2002.

Part 2 of the study is a safety run-in and expansion study of OTX-2002 participants with HCC will be administered OTX-2002 in combination with tyrosine kinase inhibitor One (Part 2A), Tyrosine Kinase Inhibitor Two (Part 2B), or Checkpoint Inhibitor (Part 2C).

A Phase 1/2 Study to Evaluate OTX-2002 in Patients With Hepatocellular Carcinoma and Other Solid Tumor Types Known for Association With the MYC Oncogene

Phase 1/2 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of OTX-2002 as a Single Agent and in Combination With Standard of Care in Patients With Hepatocellular Carcinoma and Other Solid Tumor Types Known for Association With the MYC Oncogene

The frequency of DLTs will be tabulated by dose for participants in the dose escalation phase, and information about all DLTs will be listed by dose.

The incidence of TEAEs, SAEs, and TEAEs leading to study drug discontinuation will be summarized for all patients.

ORR (proportion of participants who achieve CR or PR), DCR (proportion of participants who achieve CR, PR, or SD)per mRECIST (for HCC) and RECIST 1.1(for solid tumors), during Parts 1, 2A, 2B,and 2C

•ORR (proportion of participants who achieve CR or PR), DCR (proportion of participants who achieve CR, PR, or SD)per irRECIST during Part 2C

Duration of Complete Response and Partial Response

Omega Therapeutics

Blood and Lymph Conditions

Immune System Diseases

Nervous System Diseases

Rare Diseases

Lymphoma

Sarcoma

Brain Neoplasms

Medulloblastoma

Neuroblastoma

Lymphosarcoma

Soft Tissue Sarcoma

* Patients will receive BMS-986158 monotherapy orally for 5 days on / 2 days off per week in 28-day cycles.
* Patients with unselected relapsed or refractory solid tumors or lymphoma

* Patients will receive BMS-986158 monotherapy orally for 5 days on / 2 days off per week in 28-day cycles.
* Patients with relapsed or refractory solid tumors or lymphoma that have defined molecular features predicted to increase sensitivity to BET inhibition

* Patients will receive BMS-986378 (also known as CC-90010) monotherapy orally for 4 days every 28 days.
* Patients with relapsed or refractory CNS tumors or CNS metastatic tumors

* Patients will receive BMS-986378 (also known as CC-90010) monotherapy orally for 4 days every 28 days.
* Patients with relapsed or refractory CNS tumors or CNS metastatic tumors that have defined molecular features predicted to increase sensitivity to BET inhibition

BMS-986158 belongs to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.

BMS-986158

BMS-986378 (also known as CC-90010) belongs to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.

BMS-986378

Steven G. DuBois, MD, MS

Arm 1 of this research study is studying an investigational drug called BMS-986158 as a possible treatment for pediatric solid tumors or lymphoma. Arm 2 of this research study is studying an investigational drug called BMS-986378 (also known as CC-90010) as a possible treatment for pediatric brain tumors or pediatric tumors that have spread to the brain.

This is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved BMS-986158 or BMS-986378 as a treatment for any disease.

BMS-986158 and BMS-986378 are currently still being studied in adults. This is the first time that BMS-986158 or BMS-986378 will be evaluated in younger children, though children 12-17 years of age may also be included in parts of adult studies of BMS-986158.

Research in the laboratory has shown that BMS-986158 and BMS-986378 may have activity against cancer cells. These drugs belong to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.

Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer

Phase 1 Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 (CC-90010) in Pediatric Cancer

Dose limiting toxicity as defined in protocol

Adverse events coded using CTCAE version 5

Plasma concentrations of BMS-986158 or BMS-986378

Gene expression levels in peripheral blood

Stand Up To Cancer

Dana-Farber Cancer Institute

Principal Investigator

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Carcinoma, Squamous Cell

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Anemia

Anus Neoplasms

Fanconi Syndrome

Fanconi Anemia

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Anal Cancer

Congenital Aplastic Anemia

SRA737 will be administered orally on each day of a 28-day cycle. Subjects will receive a single dose of SRA737 between 4 to 7 days prior to starting the first cycle for PK profiling. Subjects can continue taking SRA737 if they are receiving clinical benefit and able to safely take the drug and follow the requirements of the study.

SRA737

The purpose of this clinical study is to establish the safety profile, determine the maximum tolerated dose (MTD) and recommend a Phase 2 dose and schedule of SRA737; and to evaluate the efficacy of SRA737 in prospectively-selected subjects with genetically-defined tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to checkpoint kinase 1 (Chk1) inhibition via synthetic lethality. Specific cancer indications that frequently harbor these genetic mutations will be studied.

SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Chk1, a key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress response. In cancer cells, intrinsic replication stress (RS) is induced by factors such as oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g. BRCA1 or FANCA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other genomic alterations. This replication stress results in persistent DNA damage and genomic instability, leading to an increased dependency on Chk1 for survival. Targeted inhibition of Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic RS.

This study has been designed to: establish the safety profile; determine the pharmacokinetic profile; identify the optimal dose, schedule, and MTD; obtain preliminary evidence of activity; and evaluate SRA737's efficacy in prospectively-selected subjects with tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition via synthetic lethality.

This clinical study consists of two phases, a Dose Escalation Phase 1 portion and a Cohort Expansion Phase 2 portion.

In the Dose Escalation Phase 1 portion, cohorts consisting initially of a single subject will receive escalating doses of SRA737, administered orally on a continuous daily dosing schedule in 28-day cycles. Once an SRA737-related Grade 2 toxicity is observed in a dose escalation cohort during Cycle 1, that cohort will be expanded to 3 to 6 subjects, and subsequent dose level cohorts will follow a rolling 6 design until the MTD has been identified.

In the Cohort Expansion Phase 2 portion, subjects with genetically-defined tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition will be prospectively enrolled into six indication-specific cohorts to explore the preliminary efficacy of SRA737. Subjects must have advanced or metastatic disease of one of the following types:

* castration-resistant prostate cancer (mCRPC);
* high grade serous ovarian cancer (HGSOC) without CCNE1 gene amplification;
* HGSOC with CCNE1 gene amplification (or alternative genetic alteration with similar functional effect);
* non-small cell lung cancer (NSCLC);
* head and neck squamous cell carcinoma (HNSCC) or squamous cell carcinoma of the anus (SCCA); and
* colorectal cancer (mCRC).

To qualify for enrolment in the Cohort Expansion Phase 2 portion, the subject's tumor must have a confirmed combination of mutations which are expected to confer sensitivity to Chk1 inhibition, determined by the Sponsor's review of genetic abnormalities detected in the following categories:

* Oncogenic drivers such as CCNE1 or MYC, etc.
* Genes involved in the DNA repair process including BRCA1, BRCA2, FANC genes, mismatch repair (MMR) genetic alterations and/or high microsatellite instability.
* Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as TP53, RAD50, etc. For patients with HNSCC or SCCA, positive human papilloma virus (HPV) status is also considered for eligibility.
* Genetic indicators of replicative stress such as gain of function/amplification of CHEK1, ATR or other related genes.

Tumor genetics will be prospectively determined using Next-Generation Sequencing.

A Phase 1/2 Trial of SRA737 in Subjects With Advanced Cancer

A Phase 1/2 Trial of SRA737 (a Chk1 Inhibitor) Administered Orally in Subjects With Advanced Cancer

Treatment-emergent adverse events (TEAEs) were reported until the safety Follow up (SFU) visit, 30 days after the last dose of SRA737 or prior to the initiation of a new anticancer treatment, whichever came first.

The highest dose at which ≤ 33% of subjects have a dose limiting toxicity (DLT) in a cohort of up to 6 subjects.

The RP2D and schedule were defined by the Cohort Review Committee at the end of the study and took all clinically relevant toxicity, PK and PDn data into account. The RP2D was to be a dose equal to or less than the MTD for the selected schedule.

The disease control rate (DCR) was defined as the number of subjects achieving complete response (CR) + partial response (PR) + stable disease (SD) per RECIST 1.1 criteria. Since no subjects achieved CR or PR in this study, the DCR represents the proportion of subjects in each group who achieved SD.

Time to progression (TTP) was defined as the time from Cycle 1 Day 1 to the earliest date of radiographic disease progression per RECIST 1.1, or if the subject did not experience disease progression, to the last imaging assessment. TTP was analyzed using the K-M method.

Progression free survival (PFS) was defined as time from Cycle 1 Day 1 to the earliest date of radiographic disease progression per RECIST 1.1 or death, whichever happened first. Censoring rules are defined in the SAP. PFS was analyzed using the K-M method.

Overall survival (OS) was defined as time from Cycle 1 Day 1 to the date of death (or date last known to be alive). OS was analyzed using the K-M method.

Sierra Oncology LLC - a GSK company

An AE was defined as any untoward, undesired, or unplanned medical occurrence in a subject administered SRA737. All AEs and SAEs were assessed for seriousness, causality, and expectedness.

As specified in the Statistical Analysis Plan, the frequency of each AE was evaluated in the overall Safety Evaluable Population (all enrolled subjects who receive at least 1 dose of SRA737) of patients with advanced solid tumors, irrespective of tumor type. All AEs collected are included in the summary.

Due to the small numbers of patients in some tumor type subgroups and with the intention of displaying the overall safety profile of SRA737 in advanced solid tumors, the frequency of each AE was evaluated in the overall Safety Evaluable Population rather than by tumor type subgroups. The Safety Evaluable Population includes all enrolled subjects who receive at least 1 dose of SRA737.

Safety Evaluable Population

Metastatic colorectal cancer (CRC) defined as histologically and/or cytologically confirmed CRC, and must have received at least 1 prior regimen for advanced/metastatic disease.

Colorectal Cancer

High grade serous ovarian cancer (HGSOC) defined as histologically confirmed high grade serous ovarian, fallopian tube or primary peritoneal cancer who were recurrent platinum intolerant, or with platinum resistant disease defined as radiological evidence of disease progression within 6 months of the last receipt of platinum based chemotherapy.

High Grade Serous Ovarian Cancer

Advanced non small cell lung cancer (NSCLC) defined as locally advanced and recurrent or metastatic, histologically confirmed NSCLC, and must have received at least 1 prior regimen for advanced/metastatic disease.

Non Small Cell Lung Cancer

Metastatic castration resistant prostate cancer (mCRPC) defined as histologically or cytologically confirmed adenocarcinoma of the prostate that has progressed after androgen deprivation therapy.

Metastatic Other Tumor Type Castration Resistant Prostate Cancer

Histologically confirmed HNSCC from any primary site; locally advanced disease (ie, persistent or progressive disease following curative intent radiation, and not a candidate for surgical salvage due to incurability or morbidity), or metastatic disease.

Head and Neck Squamous Cell Carcinoma

Any locally advanced or metastatic, histologically or cytologically proven solid tumor or NHL, that had relapsed after or progressing despite conventional treatment for which no conventional therapy was considered appropriate by the investigator or had been declined by the subject.

Other Tumor Type

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Not Reported

Race/Ethnicity, Customized

United Kingdom

Region of Enrollment

The Safety Evaluable Population includes all enrolled subjects who receive at least 1 dose of SRA737.

GSK Response Center

As specified in the Statistical Analysis Plan, the frequency of each AE was evaluated in the overall Safety Evaluable Population rather than by tumor type subgroups with the intention of displaying the overall safety profile of SRA737 in advanced solid tumors. The Safety Evaluable Population includes all enrolled subjects who receive at least 1 dose of SRA737.

Number of Subjects With Adverse Events as Assessed by CTCAE 4.03

The Dose Escalation Phase included a total of 18 subjects in 9 different dosage cohorts: 20 mg QD, 40 mg QD, 80 mg QD, 160 mg QD, 300 mg QD, 600 mg QD, 1000 mg QD, 500 mg BID, and 1300 mg QD.

Dose Escalation Phase

In order to determine the MTD, a total of 18 subjects were enrolled in the dose escalation phase of the study in 9 dosage cohorts. All subjects receiving at least 75% of planned doses of SRA737 within Cycle 1 and those subjects receiving less than these planned doses of SRA737 due to DLT were considered evaluable for dose review decisions.

Maximum Tolerated Dose of SRA737

All 107 subjects treated in the study were included in the review of toxicity, PK and PDn, data in order to determine the RP2D. All clinically relevant toxicity, PK and PDn data up to 30 days after last dose of SRA737 were taken into account.

Recommended Phase 2 Dose of SRA737

The Response Evaluable Population (REP) included all enrolled subjects who satisfy all of the following conditions:

1. Measurable disease and assessment at baseline
2. Received at least 75% of 1 cycle of study medication, based on dosing information
3. At least one post baseline disease assessment OR discontinued treatment due to AE or disease progression or death

Disease Control Rate (DCR) of SRA737

Time to Progression (TTP)

Progression Free Survival (PFS)

Metastatic Castration Resistant Prostate Cancer

All subjects included in the Response Evaluable Population

Overall

The Response Evaluable Population (REP) included all subjects who satisfy the following conditions:

1. Measurable disease and assessment at baseline
2. Received at least 75% of 1 cycle of study medication, based on dosing information
3. At least 1 post baseline disease assessment OR discontinued treatment due to AE or disease progression or death Note: The median OS was not estimated in the mCRPC, HNSCC, or "Other" tumor type subgroups due to insufficient number of participants with events.

Overall Survival (OS)

Overall Study

Pancreatic Neoplasms

Carcinoma, Adenosquamous

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Reproductive Control Agents

Pancrelipase

Pancreatin

Triptolide

14-O-phosphonooxymethyltriptolide disodium salt

Antineoplastic Agents, Alkylating

Alkylating Agents

Minnelide 2mg Days 1-21 of 28 day cycle (x12)

Administered orally (2 mg) once daily for 21 days of 28-day cycles for 12 cycles.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1/2 Study to Evaluate OTX-2002 in Patients With Hepatocellular Carcinoma and Other Solid Tumor Types Known for Association With the MYC Oncogene	NCT05497453	Hepatocellular ... Solid Tumor Hepatocellular ... Hepatocellular ... Hepatocellular ... Liver Cancer Liver, Cancer o...	OTX-2002 Tyrosine kinase... Tyrosine kinase... Checkpoint Inhi...	18 Years -	Omega Therapeutics
Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer	NCT03936465	Solid Tumor, Ch... Lymphoma Brain Tumor, Pe...	BMS-986158 BMS-986378	1 Year - 21 Years	Dana-Farber Cancer Institute
A Phase 1/2 Trial of SRA737 in Subjects With Advanced Cancer	NCT02797964	Advanced Solid ...	SRA737	18 Years -	Sierra Oncology LLC - a GSK company
A Phase 1/2 Trial of SRA737 in Subjects With Advanced Cancer	NCT02797964	Advanced Solid ...	SRA737	18 Years -	Sierra Oncology LLC - a GSK company
Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP)	NCT04896073	Adenosquamous C...	Minnelide	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for myc

Every month we try and update this database with for myc 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.

Spots Global Cancer Trial Database for myc

Every month we try and update this database with for myc 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.

Every month we try and update this database with for myc 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.