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

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Prostatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Neoplasms

Respiratory Tract Infections

Ovarian Cancer

Ovarian Epithelial Cancer

Pancreatic Cancer

Immunomodulating Agents

MDK-703 will be administered in sequential ascending doses as a monotherapy until unacceptable toxicity, disease progression, or withdrawal of consent.

MDK-703 will be administered in sequential ascending doses in combination with a checkpoint inhibitor until unacceptable toxicity, disease progression, or withdrawal of consent.

MDK-703 will be administered as specified under Arm description.

MDK-703

Checkpoint inhibitor will be administered as specified under Arm description.

Joseph Leveque, MD

This is an open-label, dose escalation and dose expansion study of MDK-703 as a monotherapy and in combination with other cancer therapies in adult study participants with advanced or metastatic solid tumors.

This is a Phase 1/2, open-label, multicenter, dose escalation and dose expansion study evaluating MDK-703 in adult study participants with advanced or metastatic solid tumors. This study will initially commence with dose escalation to evaluate the safety/tolerability of MDK-703 as a monotherapy and in combination with other cancer therapies. Once the monotherapy and/or combination therapy maximum tolerated dose (MTD), optimal biological dose (OBD), and/or recommended dose (RD) has been determined, then dose expansion of MDK-703 may commence in select populations of interest. The study will also evaluate the anti-tumor activity and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of MDK-703 as a monotherapy and in combination with other cancer therapies.

Multiple ascending dose escalation followed by dose expansion.

A Dose Escalation/Expansion Study of MDK-703 in Patients With Advanced or Metastatic Solid Tumors

A Phase 1/2, Open-Label, Multicenter Study of MDK-703 as a Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced or Metastatic Solid Tumors (ORCHID-1)

Based on toxicities observed from time of first dose through first cycle of treatment

Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5.0

Based on assessment of radiographic imaging per RECIST version 1.1

Blood concentration of MDK-703 at various timepoints

Time to achieve maximum blood concentration of MDK-703

Medikine, Inc.

Sarcoma

Virus Diseases

Chondrosarcoma

Adenoviridae Infections

Neoplasms, Connective and Soft Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Subjects will be treated with AdAPT-001 as a single injection, one time.

6 subjects will be enrolled in the Lead In Cohort. A Safety Analysis will be performed after 6 subjects have received at least 24 doses. Upon Safety team review as a continuous reassessment of safety, an additional 19 subjects may be enrolled. All subjects in PART 2 will receive injections of AdAPT-001 on Days 1 and 15 of 28-day cycles.

Up to 45 subjects will be enrolled in the expansion cohort to receive either AdAPT-001 on Days 1 and 15 of 28-day cycles or AdAPT-001 on Days 1 and 15 plus a checkpoint inhibitor of 28-day cycles.

Approximately 55 to 80 subjects with advanced solid tumors including sarcoma to receive either AdAPT-001 on Days 1 and 15 of 28-day cycles or AdAPT-001 on Days 1 and 15 plus a checkpoint inhibitor of 28-day cycles..

Oncolytic virus administered by intratumoral injection

AdAPT-001

Checkpoint Inhibitor per investigator discretion based on diagnosis and subject tolerability

Jeannie Williams

Alberto Bessudo, MD

Brielle Eble

Brian Gastman, MD

Minal Barve, MD

Anthony P Conley, MD

Bryan Oronsky, MD PhD

AdAPT-001 is an oncolytic virus that is injected directly into the tumor or via intraarterial administration. The purpose of this study is to find out if AdAPT-001 is safe and tolerable. The next step is to find out if AdAPT-001 if efficacious with or without a checkpoint inhibitor.

This is a dose escalation protocol to determine, first and foremost, the safety, tolerability and feasibility of intratumoral administration of AdAPT-001.

The study has 3 parts. Different groups of patients will participate in each part.

PHASE 1 PART 1: Dose Escalation Safety Run-In (CLOSED - Enrollment Completed) During PART 1, all participants will be treated with AdAPT-001 as a single injection, one time. Participants will be assigned to different dose levels to find the highest dose of AdAPT-001 that is safe and tolerable.

PHASE 1 PART 2: Dose Expansion Single-Agent (CLOSED - Enrollment Completed) All participants in PART 2 will receive injections of AdAPT-001 on Days 1 and 15 of 28-day cycles.

PHASE 1 PART 3: Expansion (CLOSED - Enrollment Completed) Subjects will be assigned to the following two arms. If a checkpoint inhibitor is indicated for the subject, the subject may be enrolled on Arm 2 per investigator discretion, otherwise subjects may be enrolled on Arm 1.

Arm 1: Intratumoral administration of AdAPT-001 (1.0 x 10¹² viral particles) on Day 1 and 15 of each 28-day cycle for up to 12 injections.

Arm 2: Intratumoral administration of AdAPT-001 (1.0 x 10¹² viral particles) on Day 1 and 15 of each 28-day cycle for up to 12 injections plus a checkpoint inhibitor per investigator discretion

PHASE 2: (OPEN to Enrollment)

Subjects with advanced solid tumors will participate in a basket two-arm parallel group evaluation (Phase 2) where eligible participants will be assigned to the following two arms based on confirmed histology by the treating investigator.

Arm 1: Confirmed Histological Diagnosis of Sarcoma Intratumoral Administration of AdAPT-001 (1.0 x 10¹² viral particles) on Day 1 and 15 of each 28-day cycle for up to 12 injections with or without a checkpoint inhibitor.

Arm 2: Confirmed Histological Diagnosis of Advanced Solid Tumor indicated to receive at least one checkpoint inhibitor.

The study is an exploratory open label single-arm interventional study using a 3 + 3 dose escalation safety run-in (PART 1) followed by a dose expansion single-agent (PART 2), followed by expansion (PART 3) single agent or single agent plus checkpoint inhibitor, followed by an adaptive designed Phase 2..

A Study of AdAPT-001 in Subjects With Sarcoma and Refractory Solid Tumors

An Adapted Phase 2a/2b, Study to Evaluate the Safety, Tolerability, and Efficacy of AdAPT-001 in Subjects With Refractory Solid Tumors

ORR and best overall response rates per Immune Response Evaluation Criteria in Solid Tumors (iRECIST)

This outcome will measure TGFβ trap concentrations in the serum and, in patients who consent to tissue collections, test for TGFβ trap expression in the treated tumors.

All subjects in PART 1 will be assessed for the development of dose-limiting toxicity (DLT) during treatment with AdAPT-001. The DLT assessment period is defined as: Day of Injection through 28 days post injection (Safety Follow Up). A DLT will be defined as any Grade 3 or higher adverse event, as assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.

In PART 1, A MTD is determined if any cohort experiences 2 subjects with DLT's.

The safety data will include adverse events, serious adverse events, performance status, clinical laboratory tests, vital signs and physical examination results.

To evaluate the efficacy of the two-arm dose regimens of AdAPT-001 in subjects with advanced solid tumors that have progressed after treatment with standard therapies or for which there are no appropriate therapies available as measured by durable (≥4 months) stable disease per Response Evaluation Criteria in Solid Tumors (RECIST).

In PART 2 and PART 3, overall response rate (ORR) and best overall response rates per response evaluation criteria outlined in Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1), as well as progression-free survival (PFS), and duration of response will be assessed.

Preliminarily to assess anti-tumor activity of AdAPT-001 by objective response rates (ORR) and best overall response rates per response evaluation criteria outlined in RECIST guideline (Version 1.1),

EpicentRx, Inc.

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Triple Negative Breast Neoplasms

Melanoma

Carcinoma, Renal Cell

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Breast Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

anti-PD-1, anti-PD-L1, or anti-CTLA-4 as a single agent or in combination with another checkpoint inhibitor or other treatment agent or modality (e.g., targeted therapy, chemotherapy, surgery, radiation, etc.) in accordance with FDA-labeled use of the agent

Hanane Arib, MS

Peter McCaffrey, MD

Diane Drobny, BSN, RN, OCN, CCRP

The microbiome has the potential to serve as a robust biomarker of clinical response to immunotherapy. Additionally, microbial manipulation, through diet, exercise, prebiotics, probiotics, or microbially-derived metabolites, may prove to be beneficial in promoting anti-tumor immune responses. However, large prospective studies in humans with longitudinal sample collection and standardized methods are needed to understand how microbiota and their byproducts affect cancer therapies, particularly among patients undergoing identical therapy but experiencing different outcomes. The proposed observational study builds upon these hypotheses by proposing a large cohort design to further assess the associations between the gut microbiota (composition and function), host immune system, and ICI treatment efficacy across multiple cancer types.

The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors

Microbiome evaluation with whole metagenome shotgun sequencing to assess changes in the relative abundance of microbial taxa (measured as percentage abundance per microbial species and changes in percentage abundance between baseline and cycle 2 timepoints) in patients who are receiving checkpoint blockade immunotherapy as the standard of care

Definition of a correlation between the gut microbiome and circulating cytokines (specifically IL-2, IL-10, TNF-alpha, IFN-gamma, and G-CSF) and therapeutic response (defined using RECIST criteria).

Definition of a correlation between the gut microbiome (measured as percent abundance of microbial taxa derived from whole-metagenome shotgun sequencing) and plasma metabolites (measured in m/z and peak intensities and--where possible--compound abundances in ng/mL) and circulating cytokines (measured in pg/mL per cytokine) in patients receiving checkpoint blockade immunotherapy.

Definition of a correlation between plasma metabolites (measured in m/z and peak intensities and--where possible--compound abundances in ng/mL) and circulating cytokines (measured in pg/mL per cytokine) and therapeutic response (defined using RECIST criteria).

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
A Dose Escalation/Expansion Study of MDK-703 in Patients With Advanced or Metastatic Solid Tumors	NCT05716295	Advanced or Met...	MDK-703 Checkpoint Inhi...	18 Years - 99 Years	Medikine, Inc.
A Dose Escalation/Expansion Study of MDK-703 in Patients With Advanced or Metastatic Solid Tumors	NCT05716295	Advanced or Met...	MDK-703 Checkpoint Inhi...	18 Years - 99 Years	Medikine, Inc.
A Study of AdAPT-001 in Subjects With Sarcoma and Refractory Solid Tumors	NCT04673942	Solid Tumor, Ad... Cancer Neoplasms Sarcoma Sarcoma,Soft Ti... Chondrosarcoma	AdAPT-001 Checkpoint Inhi...	18 Years -	EpicentRx, Inc.
The Gut Microbiome and Immune Checkpoint Inhibitor Therapy in Solid Tumors	NCT05037825	Non-Small-Cell ... Malignant Melan... Renal Cell Carc... Triple-Negative...	Checkpoint Inhi...	18 Years -	VastBiome

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