Clinical trial NCT06778863: A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Unresectable Solid Tumor
Metastatic Solid Tumor
Colorectal Adenocarcinoma
Pancreatic Adenocarcinoma
Lung Cancer
Ovarian Cancer
Breast Cancer
Head and Neck Squamous Cell Carcinoma
Prostate Cancer
Bladder Cancer
Keywords: CLSP-1025
T Cell Engager
TCE
TP53
Lead sponsor: Clasp Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-16
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Part A: Determine the maximum tolerated dose (MTD) and/or the recommended dose(s) for expansion (RDE[s])
timeFrame: 28 days after infusion
measure: 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
timeFrame: Up to 24 months after infusion
Secondary outcomes:
measure: Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0
timeFrame: Up to 24 months after infusion
measure: Number of patients with treatment-related adverse events, as assessed by CTCAE, v5.0
timeFrame: Up to 24 months after infusion
measure: Number of patients with clinically significant changes in QTcF Interval
timeFrame: Up to 24 months after infusion
measure: Maximum plasma concentration (Cmax) of CLSP-1025
timeFrame: Pre-dose and up to 168 hours post-dose
measure: Minimum plasma concentration (Cmin) of CLSP-1025
timeFrame: Pre-dose and up to 168 hours post-dose
measure: Area under the curve at the end of the dosing interval (AUCtau) of CLSP-1025
timeFrame: Pre-dose and up to 168 hours post-dose
measure: Half-life (t1/2) of CLSP-1025
timeFrame: Pre-dose and up to 168 hours post-dose
measure: Assess the immunogenicity of CLSP-1025
timeFrame: Up to 24 months after infusion
measure: Part A: Objective Response Rate (ORR)
timeFrame: Up to 24 months after infusion
measure: Duration of response (DOR)
timeFrame: Up to 24 months after infusion
measure: Time to Response
timeFrame: Up to 24 months after infusion
measure: Disease Control Rate
timeFrame: Up to 24 months after infusion
measure: Progression-free survival (PFS)
timeFrame: Up to 24 months after infusion
measure: Time of Treatment
timeFrame: Up to 24 months after infusion
measure: Overall Survival (OS)
timeFrame: Up to 24 months after infusion
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC - Norris Comprehensive Cancer Center
state: California
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI) Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References: