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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06778863
- Acronym / sponsor ID
- GUARDIAN-101 / CLSP-1025-101
- Conditions
- Advanced Solid Tumor, Unresectable Solid Tumor, Metastatic Solid Tumor, Colorectal Adenocarcinoma, Pancreatic Adenocarcinoma, Lung Cancer
- Keywords
- CLSP-1025, T Cell Engager, TCE, TP53
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Clasp Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Feb 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 16 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: Monotherapy Dose Escalation of CLSP-1025 | Experimental | Drug: CLSP-1025Dose escalation of CLSP-1025 in HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation |
| Part B: Monotherapy Dose Expansion of CLSP-1025 | Experimental | Drug: CLSP-1025Dose expansion of CLSP-1025 in HLA-A*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CLSP-1025CLSP-1025 will be administered by IV infusion | Drug | Part A: Monotherapy Dose Escalation of CLSP-1025, Part B: Monotherapy Dose Expansion of CLSP-1025 |
Primary outcome
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
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
15 secondary outcomes
Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0
Time frame: 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
Number of patients with clinically significant changes in QTcF Interval
Time frame: Up to 24 months after infusion
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
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
Time frame: 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
Assess the immunogenicity of CLSP-1025
Time frame: Up to 24 months after infusion
Part A: Objective Response Rate (ORR)
Time frame: Up to 24 months after infusion
Duration of response (DOR)
Time frame: Up to 24 months after infusion
Time to Response
Time frame: Up to 24 months after infusion
Disease Control Rate
Time frame: Up to 24 months after infusion
Progression-free survival (PFS)
Time frame: Up to 24 months after infusion
Time of Treatment
Time frame: Up to 24 months after infusion
Overall Survival (OS)
Time frame: Up to 24 months after infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lauren Harshman, MD (+1-617-812-1431, LHarshman@clasptx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Determine the maximum tolerated dose (MTD) and/or the recommended dose(s) for expansion (RDE[s]) (time frame: 28 days after infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.