A Study of CLSP 5282 in HLA-A*03:01 Positive Adult Patients With Solid Tumors (SENTINEL-101)

SENTINEL-101: A Phase 1 Dose Escalation and Expansion Study of CLSP-5282 in HLA-A*03:01 Positive Adult Patients With Solid Tumors That Harbor the KRas G12V Mutation

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Non Small Cell Lung Cancer; Advanced Solid Tumor; Pancreatic Carcinoma
• Intervention / Treatment: Drug: CLSP-5282

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.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lauren Harshman, MD; Phone Number: +1-617-812-1431; Email: LHarshman@clasptx.com
• Study Contact Backup: Name: Lauren Harshman

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27701
      • Duke Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Sidney Kimmel Cancer Center
      • Contact: Aliya Rogers; Email: axr028@jefferson.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (SCRI) Oncology Partners
      • Contact: Phone Number: 615-329-7640
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
      • Contact: Phone Number: 972-566-3000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Monotherapy Dose Escalation; Dose Escalation of CLSP-5282 in HLA A*03:01-positive adult patients with advanced solid tumors that harbor the KRas G12V mutation.	Drug: CLSP-5282; CLSP-5282 to be administered by IV infusion
Experimental: Part B Monotherapy Expansion; Dose expansion of CLSP-5282 in 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 conducted at the RDE.	Drug: CLSP-5282; CLSP-5282 to be administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A Monotherapy Dose Escalation	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]).	28 days after infusion
Part B Monotherapy Expansion	To evaluate the preliminary antitumor activity of CLSP-5282	Up to 24 months after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with treatment-emergent adverse events, as assessed by CTCAE, v5.0	Incidence and severity of treatment-emergent adverse events (TEAEs)	Up to 30 days after last infusion
Number of patients with treatment-related adverse events, as assessed by CTCAE, v5.0	Incidence and severity of treatment-related adverse events (TRAEs)	Up to 30 days after last infusion
Determine Maximum Plasma Concentration of CLSP-5282	Determine the plasma PK parameters (Cmax) of CLSP-5282	Pre-dose and up to 168 hours post-dose
Half-life (t1/2) of CLSP-5282	To determine the half-life (t1/2) of CLSP-5282	Pre-dose and up to 168 hours post-dose
Assess the immunogenicity of CLSP-5282	To determine the presence of anti-CLSP-5282 antibodies at baseline and on treatment	Up to 24 months after infusion
Part A: Objective Response Rate (ORR)	Determine Objective Response Rate (ORR) per RECIST V1.1.	Up to 24 months after infusion
Duration of response (DOR)	Determine DOR of CLSP-5282 until radiographic disease progression per RECIST V1.1 or death.	Up to 24 months after infusion
Time to Response	Determine time to response of CLSP-5282 per RECIST V1.1.	Up to 24 months after infusion
Disease Control Rate	Determine disease control rate of CLSP-5282 per RECIST V1.1.	Up to 24 months after infusion
Progression-free survival (PFS)	Determine PFS of CLSP-5282 until radiographic disease progression per RECIST V1.1 or death.	Up to 24 months after infusion
Time on Treatment	Determine Time on Treatment of CLSP-5282 from first dose to last dose.	Up to 24 months after infusion
Overall Survival (OS)	Determine OS of CLSP-5282 until death.	Up to 24 months after infusion

Collaborators and Investigators

• Sponsor: Clasp Therapeutics, Inc.
• Investigators: Study Director: Lauren Harshman, MD, Clasp Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 10, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: TCE; T-Cell Engager; Clasp-5282; KRas G12V mutation; HLA A*03:01
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CLSP-5282-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No