Advanced Solid Tumor, Bladder Cancer, Breast Cancer, Colorectal Adenocarcinoma, Head and Neck Squamous Cell Carcinoma, Lung Cancer, Metastatic Solid Tumor, Ovarian Cancer, Pancreatic Adenocarcinoma, Prostate Cancer, Unresectable Solid Tumor
Conditions
Keywords
CLSP-1025, T Cell Engager, TCE, TP53
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).
Interventions
DRUGCLSP-1025
CLSP-1025 will be administered by IV infusion
Sponsors
Clasp Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Determine the maximum tolerated dose (MTD) and/or the recommended dose(s) for expansion (RDE[s]) | 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 | Up to 24 months after infusion | Objective response rate (ORR) per RECIST V1.1 determined by Investigator assessment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0 | Up to 24 months after infusion | Incidence and severity of treatment-emergent adverse events (TEAEs) |
| Number of patients with treatment-related adverse events, as assessed by CTCAE, v5.0 | Up to 24 months after infusion | Incidence and severity of treatment-related adverse events (TRAEs) |
| Number of patients with clinically significant changes in QTcF Interval | Up to 24 months after infusion | Incidence of clinically significant changes in QTcF Interval |
| Maximum plasma concentration (Cmax) of CLSP-1025 | Pre-dose and up to 168 hours post-dose | To determine the maximum plasma concentration (Cmax) of CLSP-1025 |
| Minimum plasma concentration (Cmin) of CLSP-1025 | Pre-dose and up to 168 hours post-dose | To determine the minimum plasma concentration (Cmin) of CLSP-1025 |
| Area under the curve at the end of the dosing interval (AUCtau) of CLSP-1025 | 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 |
| Half-life (t1/2) of CLSP-1025 | Pre-dose and up to 168 hours post-dose | To determine the half-life (t1/2) of CLSP-1025 |
| Assess the immunogenicity of CLSP-1025 | Up to 24 months after infusion | To determine the presence of anti-CLSP-1025 antibodies at baseline and on treatment |
| Part A: Objective Response Rate (ORR) | Up to 24 months after infusion | Determine Objective Response Rate (ORR) per RECIST V1.1 |
| Duration of response (DOR) | Up to 24 months after infusion | Determine DOR of CLSP-1025 until radiographic disease progression per RECIST V1.1 or death |
| Time to Response | Up to 24 months after infusion | Determine time to response of CLSP-1025 per RECIST V1.1. |
| Disease Control Rate | Up to 24 months after infusion | Determine disease control rate of CLSP-1025 per RECIST V1.1. |
| Progression-free survival (PFS) | Up to 24 months after infusion | Determine PFS of CLSP-1025 until radiographic disease progression per RECIST V1.1 or death. |
| Time of Treatment | Up to 24 months after infusion | Determine Time on Treatment of CLSP-1025 from first dose to last dose |
| Overall Survival (OS) | Up to 24 months after infusion | Determine OS of CLSP-1025 until death |
Countries
United States
Contacts
CONTACTLauren Harshman, MD
Outcome results
None listed