Clinical trial NCT06971523: A Phase I/II Clinical Study of CTS3497 in Patients With MTAP Deficient Malignacies
Official title: A Multi-center, Open-label, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of CTS3497 in Patients With MTAP Deficient Advanced Solid Tumors and Lymphomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Lymphoma
Keywords: PRMT5
Lead sponsor: CytosinLab Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-05-14
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase I: Number of Patients Who Experience a Dose-Limiting Toxicity (DLT)
timeFrame: Up to 21 days after the first administration.
measure: Phase I: Number of Patients Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Baseline through 28 days after the end of treatment, estimated up to 52 weeks.
measure: Phase II: Objective Response Rate (ORR)
timeFrame: up to 48 weeks.
Secondary outcomes:
measure: Cmax of CTS3497
timeFrame: 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
measure: Tmax of CTS3497
timeFrame: 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
measure: AUC of CTS3497
timeFrame: 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
measure: Disease control rate (DCR)
timeFrame: up to 48 weeks.
measure: Duration of Response (DoR)
timeFrame: Estimated up to 48 weeks.
measure: Progression-Free Survival (PFS)
timeFrame: Estimated up to 48 weeks.
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years.
measure: Pharmacodynamic (PD) characteristics of CTS3497: symmetric dimethylarginine (SDMA)
timeFrame: 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 and Cycle 7 Day 1
measure: Pharmacodynamic (PD) characteristics and efficacy analysis.
timeFrame: Estimated up to 48 weeks.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: CytosinLab Therapeutics Co., Ltd.
name: Haiping Wu, PhD
role: STUDY_CHAIR
References: