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NCT Number: NCT06778863

A 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.

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Key information

Conditions

Advanced Solid Tumor Adnexal Diseases Bladder Cancer Breast Cancer Breast Diseases Breast Neoplasms Carcinoma Carcinoma, Squamous Cell Colorectal Adenocarcinoma Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Gonadal Disorders Head and Neck Neoplasms Head and Neck Squamous Cell Carcinoma Lung Cancer Lung Diseases Lung Neoplasms Male Urogenital Diseases Metastatic Solid Tumor Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplastic Processes Ovarian Cancer Ovarian Diseases Ovarian Neoplasms Pancreatic Adenocarcinoma Pathologic Processes Pathological Conditions, Signs and Symptoms Prostate Cancer Prostatic Diseases Prostatic Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Squamous Cell Carcinoma of Head and Neck Thoracic Neoplasms Unresectable Solid Tumor Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

HonorHealth Research Institute, Scottsdale, Arizona, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CLSP-1025

Drug

CLSP-1025 will be administered by IV infusion

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 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)

  2. 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)

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Part A: Objective Response Rate (ORR)

    Time frame: Up to 24 months after infusion

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

  10. 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

  11. Time to Response

    Time frame: Up to 24 months after infusion

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

  12. Disease Control Rate

    Time frame: Up to 24 months after infusion

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

  13. 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.

  14. Time of Treatment

    Time frame: Up to 24 months after infusion

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

  15. Overall Survival (OS)

    Time frame: Up to 24 months after infusion

    Determine OS of CLSP-1025 until death

Study contacts

Contact information is provided by the study sponsor or research team.

Lauren Harshman, MD

CONTACT

[email protected]

+1-617-812-1431

Sponsors and collaborators

Lead sponsor

Clasp Therapeutics, Inc.

Industry

Registry information

Official study title

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

Acronym: GUARDIAN-101

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Jan 16, 2025
Registry last updated
Feb 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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