A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation (GUARDIAN-101)

February 12, 2026 updated by: Clasp Therapeutics, Inc.

GUARDIAN-101: A Phase 1 Dose Escalation and Expansion Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Estimated)

90

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • HonorHealth Research Institute
        • Contact:
          • Phone Number: 833-354-6667
      • Tucson, Arizona, United States, 85719
    • California
      • Los Angeles, California, United States, 90033
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California Davis Comprehensive Cancer Center
        • Contact:
          • Phone Number: 916-703-5558
      • San Francisco, California, United States, 94143
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami - Sylvester Comprehensive Cancer Center
        • Contact:
          • Phone Number: 407-765-9589
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • The University of Chicago Comprehensive Cancer Center
        • Contact:
          • Phone Number: 855-403-0533
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky Markey Cancer Center
        • Contact:
          • Phone Number: 859-257-4488
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
        • Contact:
          • Phone Number: 410-955-8964
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Contact:
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Health
        • Contact:
          • Phone Number: 212-263-4432
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Phone Number: 646-608-4042
    • North Carolina
      • Durham, North Carolina, United States, 27701
        • Recruiting
        • Duke Cancer Institute
        • Contact:
          • Phone Number: 866-385-3123
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
        • Contact:
          • Phone Number: 215-214-1515
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University, Sidney Kimmel Cancer Center
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
        • Contact:
          • Phone Number: 615-936-8422
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute (SCRI) Oncology Partners
        • Contact:
          • Phone Number: 615-329-7640
    • Texas
      • Dallas, Texas, United States, 75230
        • Recruiting
        • Mary Crowley Cancer Research
        • Contact:
          • Phone Number: 972-566-3000
      • Dallas, Texas, United States, 75246
        • Recruiting
        • Baylor University Medical Center
        • Contact:
          • Phone Number: 888-507-3732
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
          • Phone Number: 888-989-5374
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
        • Contact:
          • Phone Number: 855-557-0555

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Monotherapy Dose Escalation of CLSP-1025
Dose escalation of CLSP-1025 in HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation
Drug: CLSP-1025
CLSP-1025 will be administered by IV infusion
Experimental: Part B: Monotherapy Dose Expansion of CLSP-1025
Dose expansion of CLSP-1025 in HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation
Drug: CLSP-1025
CLSP-1025 will be administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Determine the maximum tolerated dose (MTD) and/or the recommended dose(s) for expansion (RDE[s])
Time Frame: 28 days after infusion
Rate of dose-limiting toxicities (DLTs) after infusion of CLSP-1025
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
Time Frame: Up to 24 months after infusion
Objective response rate (ORR) per RECIST V1.1 determined by Investigator assessment
Up to 24 months after infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0
Time Frame: Up to 24 months after infusion
Incidence and severity of treatment-emergent adverse events (TEAEs)
Up to 24 months after infusion
Number of patients with treatment-related adverse events, as assessed by CTCAE, v5.0
Time Frame: Up to 24 months after infusion
Incidence and severity of treatment-related adverse events (TRAEs)
Up to 24 months after infusion
Number of patients with clinically significant changes in QTcF Interval
Time Frame: Up to 24 months after infusion
Incidence of clinically significant changes in QTcF Interval
Up to 24 months after infusion
Maximum plasma concentration (Cmax) of CLSP-1025
Time Frame: Pre-dose and up to 168 hours post-dose
To determine the maximum plasma concentration (Cmax) of CLSP-1025
Pre-dose and up to 168 hours post-dose
Minimum plasma concentration (Cmin) of CLSP-1025
Time Frame: Pre-dose and up to 168 hours post-dose
To determine the minimum plasma concentration (Cmin) of CLSP-1025
Pre-dose and up to 168 hours post-dose
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
To determine the area under the curve at the end of the dosing interval (AUCtau) of CLSP-1025
Pre-dose and up to 168 hours post-dose
Half-life (t1/2) of CLSP-1025
Time Frame: Pre-dose and up to 168 hours post-dose
To determine the half-life (t1/2) of CLSP-1025
Pre-dose and up to 168 hours post-dose
Assess the immunogenicity of CLSP-1025
Time Frame: Up to 24 months after infusion
To determine the presence of anti-CLSP-1025 antibodies at baseline and on treatment
Up to 24 months after infusion
Part A: Objective Response Rate (ORR)
Time Frame: Up to 24 months after infusion
Determine Objective Response Rate (ORR) per RECIST V1.1
Up to 24 months after infusion
Duration of response (DOR)
Time Frame: Up to 24 months after infusion
Determine DOR of CLSP-1025 until radiographic disease progression per RECIST V1.1 or death
Up to 24 months after infusion
Time to Response
Time Frame: Up to 24 months after infusion
Determine time to response of CLSP-1025 per RECIST V1.1.
Up to 24 months after infusion
Disease Control Rate
Time Frame: Up to 24 months after infusion
Determine disease control rate of CLSP-1025 per RECIST V1.1.
Up to 24 months after infusion
Progression-free survival (PFS)
Time Frame: Up to 24 months after infusion
Determine PFS of CLSP-1025 until radiographic disease progression per RECIST V1.1 or death.
Up to 24 months after infusion
Time of Treatment
Time Frame: Up to 24 months after infusion
Determine Time on Treatment of CLSP-1025 from first dose to last dose
Up to 24 months after infusion
Overall Survival (OS)
Time Frame: Up to 24 months after infusion
Determine OS of CLSP-1025 until death
Up to 24 months after infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clasp Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 28, 2025

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

January 8, 2025

First Submitted That Met QC Criteria

January 12, 2025

First Posted (Actual)

January 16, 2025

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 12, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLSP-1025-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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