Advanced Solid TumorPhase 1GUARDIAN-101NCT06778863
A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation
A Phase 1 study testing CLSP-1025 in people with Advanced Solid Tumor and Unresectable Solid Tumor, run by Clasp Therapeutics, Inc. at 21 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Unresectable Solid Tumor, Metastatic Solid Tumor
- What is being tested?
- CLSP-1025
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 21 sitesUnited States
- Study dates
- 28 Feb 2025to Jun 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
21 sites in 1 country. Contact the study team or a site near you to ask about taking part.
21 sites in 1 country
United States21 sites, 21 recruiting
- Recruiting
Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
410-955-8964
- Recruiting
The University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
855-403-0533
- Recruiting
Mary Crowley Cancer Research
Dallas, Texas, 75230
972-566-3000
- Recruiting
Baylor University Medical Center
Dallas, Texas, 75246
888-507-3732
- Recruiting
Duke Cancer Institute
Durham, North Carolina, 27701
866-385-3123
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Oncology Clinical Research Referral Office, 551-996-1777, OncologyResearchReferral@hmhn.org
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
888-989-5374
- Recruiting
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
859-257-4488
- Recruiting
USC - Norris Comprehensive Cancer Center
Los Angeles, California, 90033
323-865-0451, clinical.trials@med.usc.edu
- Recruiting
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
407-765-9589
- Recruiting
Sarah Cannon Research Institute (SCRI) Oncology Partners
Nashville, Tennessee, 37203
615-329-7640
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
615-936-8422
- Recruiting
NYU Langone Health
New York, New York, 10016
212-263-4432
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
646-608-4042
- Recruiting
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
Aliya Rogers, axr028@jefferson.edu
- Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
215-214-1515
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
916-703-5558
- Recruiting
University of California San Francisco
San Francisco, California, 94143
hdfccc.cip@ucsf.edu
- Recruiting
HonorHealth Research Institute
Scottsdale, Arizona, 85258
833-354-6667
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
855-557-0555
- Recruiting
The University of Arizona Cancer Center
Tucson, Arizona, 85719
UACC-ClinicalTrialsInfo@arizona.edu
About this study
Official 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
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.
Read the 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).
- Conditions
- Advanced Solid Tumor, Unresectable Solid Tumor, Metastatic Solid Tumor, Colorectal Adenocarcinoma, Pancreatic Adenocarcinoma, Lung Cancer
- Being tested
- CLSP-1025
- Keywords
- CLSP-1025, T Cell Engager, TCE, TP53
- Medical subject headings
- Neoplasm Metastasis, Lung Neoplasms, Ovarian Neoplasms, Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck, Prostatic Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLSP-1025Drug
CLSP-1025 will be administered by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part A: Monotherapy Dose Escalation of CLSP-1025 | Experimental | Dose escalation of CLSP-1025 in HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation Receives: Drug: CLSP-1025 |
| Part B: Monotherapy Dose Expansion of CLSP-1025 | Experimental | Dose expansion of CLSP-1025 in HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation Receives: Drug: CLSP-1025 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Up to 24 months after infusion
Secondary outcomes (15)
Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0
Incidence and severity of treatment-emergent adverse events (TEAEs)
Measured: 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)
Measured: Up to 24 months after infusion
Number of patients with clinically significant changes in QTcF Interval
Incidence of clinically significant changes in QTcF Interval
Measured: Up to 24 months after infusion
Maximum plasma concentration (Cmax) of CLSP-1025
To determine the maximum plasma concentration (Cmax) of CLSP-1025
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 24 months after infusion
Part A: Objective Response Rate (ORR)
Determine Objective Response Rate (ORR) per RECIST V1.1
Measured: 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
Measured: Up to 24 months after infusion
Time to Response
Determine time to response of CLSP-1025 per RECIST V1.1.
Measured: Up to 24 months after infusion
Disease Control Rate
Determine disease control rate of CLSP-1025 per RECIST V1.1.
Measured: 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.
Measured: Up to 24 months after infusion
Time of Treatment
Determine Time on Treatment of CLSP-1025 from first dose to last dose
Measured: Up to 24 months after infusion
Overall Survival (OS)
Determine OS of CLSP-1025 until death
Measured: Up to 24 months after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2025
- Study start28 Feb 2025
- Primary completionDec 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clasp Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06778863
- Sponsor's protocol ID
- CLSP-1025-101
- Acronym
- GUARDIAN-101
- Status last verified
- Feb 2026
- First submitted
- 8 Jan 2025
- Last updated
- 13 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No