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

CytosinLab Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Solid Tumor; Lymphoma

Treatments: Drug: CTS3497

Study type: Interventional

Funder types: Industry

Identifiers

NCT06971523

CTS3497-CI01

Details and patient eligibility

About

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.

Full description

The primary objective of Phase I of this study is to evaluate the safety, tolerability, PK, PD and efficacy 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 and safety of CTS3497 in patients with metastatic or locally advanced MTAP-deficient solid tumors and lymphomas.

Enrollment: 224 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥ 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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224 participants in 2 patient groups

Phase I: CTS3497 Monotherapy Dose Escalation/Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: CTS3497

Phase II: CTS3497 Monotherapy Expansion

Experimental group

Description:

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.

Treatment:

Drug: CTS3497