Advanced Solid Tumor, Colorectal Cancer, Non Small Cell Lung Cancer, Pancreatic Carcinoma
Conditions
Keywords
T-Cell Engager, TCE, Clasp-5282, KRas G12V mutation, HLA A*03:01
Brief summary
Phase 1, open-label, multicenter study to evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of CLSP 5282 when administered to HLA A\*03:01-positive adult patients with advanced solid tumors that harbor the KRas G12V mutation.
Detailed description
CLSP-5282-101 is a Phase 1, open-label, multicenter study designed to evaluate the safety, tolerability, PK, PD, and preliminary clinical activity of CLSP-5282 when administered to HLA A\*03:01-positive adult patients with advanced solid tumors that harbor the KRas G12V mutation. The study will be conducted in 2 parts: Part A Monotherapy Dose Escalation to determine the MTD and/or RDE(s) to characterize safety and clinical activity of CLSP-5282. Part B Monotherapy Expansion to explore the preliminary antitumor activity and further characterize the safety, tolerability, PK, and PD of CLSP-5282 at the RDE(s). Part B will include three indication-specific cohorts in pancreatic adenocarcinoma (PDAC), colorectal cancer (CRC), and non-small cell lung carcinoma (NSCLC) as well as an all-other solid tumor cohort.
Interventions
DRUGCLSP-5282
CLSP-5282 to 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
* Adults at least 18 years of age on the day of signing informed consent. * Willing and able to provide written informed consent for the study. * Histologically or cytologically diagnosed, locally advanced or metastatic solid tumors that have progressed after standard of care therapy or for which no standard therapy exists. * Tumors must harbor the KRas G12V mutation confirmed by the site's local or preferred tissue or ctDNA testing platform in an accredited laboratory. * Patients must be HLA-A\*03:01 positive by central assay. * Eastern Cooperative Oncology Group performance status of 0 or 1. * 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.
Exclusion criteria
* Patients who have received other KRas G12V directed cellular therapies or TCEs. * Patients may not be on other anticancer therapies at the time of the first dose of CLSP-5282. Exceptions upon agreement with Sponsor. * Any other primary malignancy within the 2 years prior to first dose of study treatment except for non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, breast), or prostate cancer in remission. * Patients who have not fully recovered from adverse events due to previous anticancer therapies * Patients with active infection requiring systemic antimicrobial therapy * Known primary malignant brain tumors, active central nervous system metastases and/or carcinomatous meningitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A Monotherapy Dose Escalation | 28 days after infusion | To characterize the safety and tolerability of CLSP-5282 and to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE\[s\]). |
| Part B Monotherapy Expansion | Up to 24 months after infusion | To evaluate the preliminary antitumor activity of CLSP-5282 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0 | Up to 30 days after last 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 30 days after last infusion | Incidence and severity of treatment-related adverse events (TRAEs) |
| Determine Maximum Plasma Concentration of CLSP-5282 | Pre-dose and up to 168 hours post-dose | Determine the plasma PK parameters (Cmax) of CLSP-5282 |
| Half-life (t1/2) of CLSP-5282 | Pre-dose and up to 168 hours post-dose | To determine the half-life (t1/2) of CLSP-5282 |
| Assess the immunogenicity of CLSP-5282 | Up to 24 months after infusion | To determine the presence of anti-CLSP-5282 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-5282 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-5282 per RECIST V1.1. |
| Disease Control Rate | Up to 24 months after infusion | Determine disease control rate of CLSP-5282 per RECIST V1.1. |
| Progression-free survival (PFS) | Up to 24 months after infusion | Determine PFS of CLSP-5282 until radiographic disease progression per RECIST V1.1 or death. |
| Time on Treatment | Up to 24 months after infusion | Determine Time on Treatment of CLSP-5282 from first dose to last dose. |
| Overall Survival (OS) | Up to 24 months after infusion | Determine OS of CLSP-5282 until death. |
Countries
United States
Contacts
CONTACTLauren Harshman, MD
CONTACTLauren Harshman
STUDY_DIRECTORLauren Harshman, MD
Clasp Therapeutics
Outcome results
None listed