A Phase I/II Clinical Study of CTS3497 in Patients With MTAP Deficient Malignacies

NCT06971523 | Recruiting Phase 1

• 1 other identifier: CTS3497-CI01
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of Phase I of this study is to evaluate the safety and tolerability, and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of CTS3497 in patients with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-deficient solid tumors and lymphomas. The primary objective of Phase II of this study is to evaluate the efficacy of CTS3497 in patients with metastatic or locally advanced MTAP-deficient solid tumors and lymphomas.

Conditions

Solid Tumor; Lymphoma

Keywords

PRMT5

Outcome Measures

Primary Outcomes (3)

• Phase I: Number of Patients Who Experience a Dose-Limiting Toxicity (DLT)

  Incidence of DLT(s) during the DLT observation period

  Up to 21 days after the first administration.

• Phase I: Number of Patients Who Experience a Treatment-emergent Adverse Event (TEAE)

  Adverse events (AEs) are defined as any untoward medical occurrence in clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs) and clinical laboratory tests will be recorded as TEAEs. Serious AEs (SAEs) are defined as any event that meets at least 1 of the following criteria: resulting in death (fatal); requiring in-patient hospitalization or prolongation of existing hospitalization; resulting in persistent or significant disability/incapacity; being a congenital anomaly/birth defect; other medically important serious event.

  Baseline through 28 days after the end of treatment, estimated up to 52 weeks.

• Phase II: Objective Response Rate (ORR)

  The percentage of participants having complete response (CR) or partial response (PR) assessed based on RECIST V1.1.

  up to 48 weeks.

Secondary Outcomes (9)

• Cmax of CTS3497

  Cycle 1 (each cycle is 21 days) Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1

• Tmax of CTS3497

  Cycle 1 (each cycle is 21 days) Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1

• AUC of CTS3497

  Cycle 1 (each cycle is 21 days) Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 5 Day 1

• Disease control rate (DCR)

  up to 48 weeks.

• Duration of Response (DoR)

  Estimated up to 48 weeks.

Study Arms (2)

Phase I: CTS3497 Monotherapy Dose Escalation/Dose Expansion

EXPERIMENTAL

7 dose groups are pre-specified in Dose Escalation,and 2-3 dose groups in Dose Expansion.

Drug: CTS3497

Phase II: CTS3497 Monotherapy Expansion

EXPERIMENTAL

CTS3497 RP2D administered to patients with MTAP homozygous deletion including the following cohorts: esophageal squamous cell carcinoma \[ESCC\], pancreatic adenocarcinoma \[PAAD\], biliary tract cancer \[BTC\], non-small cell lung carcinoma\[NSCLC\], malignant pleural mesothelioma \[MPM\], Urothelial cancer, high-grade gliomas, other solid tumors, and lymphomas.

Drug: CTS3497

Interventions

CTS3497 DRUG

CTS3497: Orally via capsules

Also known as: CTS3497 capsules

Phase I: CTS3497 Monotherapy Dose Escalation/Dose Expansion; Phase II: CTS3497 Monotherapy Expansion

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age at the signing of ICF.
• Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who cannot be treated surgically and have failed standard of care (SoC). Or patients with refractory/relapsed lymphomas.
• MTAP deficiency is confirmed by IHC or NGS.
• At least one evaluable tumor lesion at screening for patients in escalation part, and at least one measurable tumor lesion for patients in expansion part.
• ECOG performance status of 0 to 1.
• Adequate hematopoietic function, cardiac function, liver function, renal function, and coagulation function per local laboratory.

You may not qualify if:

• Female patients in pregnancy or lactation.
• Patients with dysphagia; or a condition that seriously affects gastrointestinal absorption.
• Allergic or intolerant to the active ingredients or excipients of the investigational product.
• Anti-tumor therapy within 28 days of study day 1.
• Prior treatment with an methionine adenosyltransferase 2α (MAT2A) inhibitor or a protein arginine methyltransferase 5 (PRMT5) inhibitor.
• Central nervous system (CNS) metastasis at screening.
• Live vaccine therapy within 4 weeks before study drug administration.
• Use of therapeutic anti-coagulation for treatment of active thromboembolic events.
• Use of prescription medications that are known strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) within 14 days or 5 half-lives (whichever is longer) before study day 1.
• Unresolved toxicity from prior anti-cancer therapy.
• Active infection of HIV, HBV or HCV.
• Patients who are judged by the investigator to have a history of other serious systemic diseases, or not suitable for participating in the trial for any other reason.

Sponsors & Collaborators

• CytosinLab Therapeutics Co., Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Haiping Wu, PhD

  CytosinLab Therapeutics Co., Ltd.

  STUDY CHAIR

Central Study Contacts

Shuning Xing, MS

CONTACT

0086-21-58920766; shuning.xing@cytosinlab.com

Jifang Gong, MD

CONTACT

0086-10-88196561; goodjf@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 14, 2025
• Study Start: December 25, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: May 14, 2025

Record last verified: 2025-04

Locations

CN (1)