A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation

Phase 1RecruitingNCT06778863

Clasp Therapeutics, Inc.90 enrolled

Overview

Phase 1 dose escalation and expansion study of CLSP-1025, a first-in-class HLA-A\*02:01 specific T cell engager (TCE) targeting solid tumors that harbor the p53 R175H mutation.

This Phase 1, open-label, multicenter study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of CLSP-1025 when administered to HLA-A\*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation. The study will be conducted in 2 parts: Part A Monotherapy Dose Escalation to determine the recommended dose(s) for expansion (RDE\[s\]) and Part B Monotherapy Expansion to explore the preliminary antitumor activity as well as further characterize the safety, tolerability, PK, and PD of CLSP-1025 at the RDE(s).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumor Unresectable Solid Tumor Metastatic Solid Tumor

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Patients must be at least 18 years of age at the time of signing the informed consent. * Patients must be willing and able to provide written informed consent * Patients must have locally advanced or metastatic solid tumors that have progressed after standard of care therapy or for which no standard therapy exists * Tumors must harbor a TP53 R175H variant mutation confirmed by an accredited laboratory-based test * Patients must be HLA-A\*02:01 positive by central assay * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment * Adequate hematological, renal and hepatic function * Per Investigator judgement, patient is willing and able to complete study visits and/or procedures per the protocol and comply with study requirements for study participation Key Exclusion Criteria: * Patients with Li-Fraumeni syndrome or other known germline p53 R175H mutation * Patients who have received other p53 R175H-directed therapies * Patients who have not fully recovered from adverse events due to previous anticancer therapies * Patients with active infection requiring systemic antimicrobial therapy * Any other primary malignancy within the 2 years prior to enrollment (except for non- melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or prostate cancer in remission. * Known active central nervous system metastases and/or carcinomatous meningitis

Locations (21)

HonorHealth Research Institute

Scottsdale, Arizona, United States

RECRUITING

The University of Arizona Cancer Center

Tucson, Arizona, United States

RECRUITING

USC - Norris Comprehensive Cancer Center

Los Angeles, California, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

RECRUITING

University of California San Francisco

San Francisco, California, United States

RECRUITING

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

RECRUITING

The University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

RECRUITING

University of Kentucky Markey Cancer Center

Lexington, Kentucky, United States

RECRUITING

Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, United States

RECRUITING

...and 11 more locations

Outcomes

Primary Outcomes

Part A: Determine the maximum tolerated dose (MTD) and/or the recommended dose(s) for expansion (RDE[s])

Rate of dose-limiting toxicities (DLTs) after infusion of CLSP-1025

Time frame: 28 days after infusion

Part B: Evaluate the Objective response rate (ORR) of CLSP-1025 as a monotherapy in HLA-selected patients with advanced solid tumors that express the p53 R175H mutation

Objective response rate (ORR) per RECIST V1.1 determined by Investigator assessment

Time frame: Up to 24 months after infusion

Secondary Outcomes

Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0

Incidence and severity of treatment-emergent adverse events (TEAEs)

Time frame: Up to 24 months after infusion

Number of patients with treatment-related adverse events, as assessed by CTCAE, v5.0

Incidence and severity of treatment-related adverse events (TRAEs)

Time frame: Up to 24 months after infusion

Number of patients with clinically significant changes in QTcF Interval

Incidence of clinically significant changes in QTcF Interval

Time frame: Up to 24 months after infusion

Maximum plasma concentration (Cmax) of CLSP-1025

To determine the maximum plasma concentration (Cmax) of CLSP-1025

Time frame: Pre-dose and up to 168 hours post-dose

Minimum plasma concentration (Cmin) of CLSP-1025

To determine the minimum plasma concentration (Cmin) of CLSP-1025

Time frame: Pre-dose and up to 168 hours post-dose

Area under the curve at the end of the dosing interval (AUCtau) of CLSP-1025

To determine the area under the curve at the end of the dosing interval (AUCtau) of CLSP-1025

Time frame: Pre-dose and up to 168 hours post-dose

Half-life (t1/2) of CLSP-1025

To determine the half-life (t1/2) of CLSP-1025

Time frame: Pre-dose and up to 168 hours post-dose

Assess the immunogenicity of CLSP-1025

To determine the presence of anti-CLSP-1025 antibodies at baseline and on treatment

Time frame: Up to 24 months after infusion

Part A: Objective Response Rate (ORR)

Determine Objective Response Rate (ORR) per RECIST V1.1

Time frame: Up to 24 months after infusion

Duration of response (DOR)

Determine DOR of CLSP-1025 until radiographic disease progression per RECIST V1.1 or death

Time frame: Up to 24 months after infusion

Time to Response

Determine time to response of CLSP-1025 per RECIST V1.1.

Time frame: Up to 24 months after infusion

Disease Control Rate

Determine disease control rate of CLSP-1025 per RECIST V1.1.

Time frame: Up to 24 months after infusion

Progression-free survival (PFS)

Determine PFS of CLSP-1025 until radiographic disease progression per RECIST V1.1 or death.

Time frame: Up to 24 months after infusion

Time of Treatment

Determine Time on Treatment of CLSP-1025 from first dose to last dose

Time frame: Up to 24 months after infusion

Overall Survival (OS)

Determine OS of CLSP-1025 until death

Time frame: Up to 24 months after infusion

A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation

Overview

Conditions

Interventions

Eligibility

Locations (21)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts