Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

Infections

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Stomach Neoplasms

Prostatic Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Lung Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Esophageal Neoplasms

Lymphoma

Triple Negative Breast Neoplasms

Uterine Cervical Neoplasms

Melanoma

Carcinoma, Renal Cell

Microsatellite Instability

Carcinoma, Transitional Cell

Lymphoma, Follicular

Lymphoma, B-Cell

Aggression

Carcinoma, Merkel Cell

Stomach Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Esophageal Cancer

Lymphosarcoma

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

Follicular Lymphoma

B-cell Lymphoma

Merkel Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Investigating VIP152 (BAY 1251152) in a dose escalation cohort in patients with solid tumors and aggressive NHL

Investigating VIP152 (BAY 1251152) in a dose expansion cohort in patients with solid tumors and aggressive NHL

Investigating combination VIP152 (BAY 1251152) and Keytruda® (pembrolizumab) in a dose escalation cohort in patients with advanced cancer. All subjects must be eligible to use pembrolizumab per USPI.

Investigating combination VIP152 (BAY 1251152) and Keytruda® (pembrolizumab) in a dose expansion cohort in patients with advanced cancer. All subjects must be eligible to use pembrolizumab per USPI.

The starting dose of Cohort 1 will be 5 mg IV (30 minute infusion) fixed dose once weekly (5 mg/week) for 21 day cycles.

VIP152 (BAY 1251152)

30 mg IV (30 minute infusion) fixed dose once weekly of a 21 day cycle.

VIP152 (BAY 1251152) 30 mg

200 mg IV fixed dose once every 3 weeks of a 21 day cycle

Keytruda

The starting dose of Cohort 3 will be 15 mg IV (30 minute infusion) fixed dose once weekly (15 mg/week) for 21 day cycles.

VIP152 (BAY 1251152) 15 mg

Vincerx Study Director

Determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of VIP152 (BAY 1251152) as monotherapy or in combination in patients with solid tumors and aggressive non-hodgkin's lymphoma (NHL).

Part 2 VIP152 Monotherapy (Global). Part 3 dose escalation with VIP152 in combination with pembrolizumab (US only). Part 4 dose expansion with VIP152 in combination with pembrolizumab (US only).

Phase I Dose Escalation Study for VIP152 in Patients With Advanced Cancer

An Open-label, Multicenter Phase I Dose Escalation Study to Characterize Safety, Tolerability, Preliminary Anti-tumor Activity, Pharmacokinetics and Maximum Tolerated Dose of VIP152 (BAY 1251152) as Monotherapy or Combination Therapy in Subjects With Advanced Cancer.

Vincerx Pharma, Inc.

Recurrence

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Amino Acids

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

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

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Anemia

Fanconi Syndrome

Fanconi Anemia

Congenital Aplastic Anemia

Prexasertib

Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Geoffrey Shapiro, MD, PhD

This research study is studying a checkpoint kinase 1 (CHK1) inhibitor as a possible treatment for advanced solid tumors that harbor genetic alterations in the homologous repair (HR) pathway, genetic alterations that indicate replication stress, or with CCNE1 amplification.

This is an open label, phase II, two-arm study exploring the anti-tumor activity of the CHK1 inhibitor prexasertib (LY2606368) in patients with advanced solid tumors exhibiting one of the following:

1. Replicative stress, including MYC amplification, CCNE1 amplification, Rb loss, or an FBXW7 mutation
2. An HR deficiency, including tumors with genomic or somatic mutations of BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, or the Fanconi anemia pathway genes
3. A CCNE1 amplification

A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency

A Phase II Study of the CHK1 Inhibitor LY2606368 in Patients With Advanced Solid Tumors Exhibiting Replicative Stress or Homologous Recombination Repair Deficiency

Progression-Free Rate defines as the percentage of participants progression-free at 4 months in all arms, by RECIST 1.1 criteria. Progression-free rate will be estimated as binomial proportion and overall survival and progression-free survival estimates and curves will be generated using the Kaplan-Meier method.

All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEvE as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Dana-Farber Cancer Institute

Geoffrey Shapiro M.D., PhD

Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Homologous Repair (HR) Deficiency Cohort

Replicative Stress Cohort

CCNE1 Amplification Cohort

Total

Age, Continuous

Sex: Female, Male

Non-Hispanic

Hispanic

Race/Ethnicity, Customized

United States

Region of Enrollment

Geoffrey Shapiro M.D., PhDDana-Farber Cancer Institute

>= 4 months

< 4 months

Progression-Free Rate at 4 Month

Incidence of Grade 4 Treatment-Related Toxicity

Objective Response Rate

Median Overall Survival (OS)

Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Overall Study

Syndrome

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Richter Syndrome

Investigating VIP152 in a monotherapy cohort in patients with high-risk CLL and Richter Syndrome

Investigating VIP152 in combination with a BTKi in patients with CLL

VIP152

BTKi

Determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of VIP152 as monotherapy or in combination with a BTKi in patients with Chronic Lymphocytic Leukemia (CLL) or Richter Syndrome

A Study to Evaluate VIP152 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Richter Syndrome

An Open-label, Multicenter Phase 1/1b Study to Characterize Safety, Tolerability, Preliminary Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of VIP152 Monotherapy or Combination Therapy in Subjects With High-risk Chronic Lymphocytic Leukemia or Richter Syndrome

Number of participants with adverse events as a measure safety and tolerability of high risk CLL and RS in monotherapy

Tumor response evaluation based on the response criteria as applicable for CLL and Richter Syndrome

Time at Which Response Criteria are Met for Complete Response or Partial Response (Whichever Occurs First) Until the First Date of Recurrence, Progression or Death per applicable response criteria

Number of Participants Without Disease Progression per iwCLL guidelines for CLL \& Lugano Classification for NHL

Maximum observed drug concentration in measured administration (Cmax) of VIP152

time from first dose to the initiation of next dose or death

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Dose Escalation Study for VIP152 in Patients With Advanced Cancer	NCT02635672	Neoplasms	VIP152 (BAY 125... VIP152 (BAY 125... Keytruda VIP152 (BAY 125...	18 Years -	Vincerx Pharma, Inc.
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
Phase I Dose Escalation Study for VIP152 in Patients With Advanced Cancer	NCT02635672	Neoplasms	VIP152 (BAY 125... VIP152 (BAY 125... Keytruda VIP152 (BAY 125...	18 Years -	Vincerx Pharma, Inc.
A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency	NCT02873975	Advanced Cancer...	LY2606368	18 Years -	Dana-Farber Cancer Institute
Phase I Dose Escalation Study for VIP152 in Patients With Advanced Cancer	NCT02635672	Neoplasms	VIP152 (BAY 125... VIP152 (BAY 125... Keytruda VIP152 (BAY 125...	18 Years -	Vincerx Pharma, Inc.
Phase I Dose Escalation Study for VIP152 in Patients With Advanced Cancer	NCT02635672	Neoplasms	VIP152 (BAY 125... VIP152 (BAY 125... Keytruda VIP152 (BAY 125...	18 Years -	Vincerx Pharma, Inc.
A Study to Evaluate VIP152 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Richter Syndrome	NCT04978779	Relapsed Non Ho... Chronic Lymphoc... Refractory Chro... Richter Syndrom... MYC Amplificati... MYC Overexpress... MYC Translocati...	VIP152 BTKi	18 Years -	Vincerx Pharma, Inc.

Spots Global Cancer Trial Database for myc amplification