CLSP-1025 for Cancer

(GUARDIAN-101 Trial)

Recruiting at 17 trial locations

Overseen By Lauren Harshman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Clasp Therapeutics, Inc.

Disqualifiers: Li-Fraumeni syndrome, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CLSP-1025, designed to target specific types of solid tumors. Researchers aim to evaluate its effectiveness for patients whose tumors have a specific DNA mutation, p53 R175H. The trial consists of two parts: one to determine the optimal dose and another to assess its efficacy at that dose. It may suit those with advanced solid tumors who have not responded to other treatments and have a confirmed p53 R175H mutation. Participants must be able to travel for study visits and adhere to trial protocols. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that CLSP-1025 is likely to be safe for humans?

Research has shown that CLSP-1025 is being tested for its safety and effectiveness in treating certain solid tumors. As an early study, it aims to assess how well participants tolerate the treatment and identify any possible side effects.

Since this is the first human trial of CLSP-1025, the primary goal is to ensure safety by closely monitoring participants for any adverse reactions. The safety data from this phase will help determine the appropriate dose and understand how the body processes the treatment.

Although specific data from past studies on CLSP-1025's safety in humans is not available, this trial is crucial for gathering that information. This stage focuses on ensuring the treatment is safe and generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for advanced solid tumors, which typically include chemotherapy, targeted therapy, and immunotherapy, CLSP-1025 is unique because it specifically targets the p53 R175H mutation. This mutation is present in certain cancer cells, making CLSP-1025 a more precise treatment option. Researchers are excited about this approach because targeting a specific mutation can lead to more effective outcomes with potentially fewer side effects compared to broad-spectrum cancer treatments. This precision medicine approach represents a significant advancement in tailoring cancer treatment to the genetic profile of a patient's tumor.

What evidence suggests that CLSP-1025 might be an effective treatment for cancer?

Research has shown that CLSP-1025 targets a specific change in cancer cells called the p53 R175H mutation, found in some solid tumors. In this trial, participants will receive CLSP-1025, which helps the body's T cells recognize and attack these cancer cells. Early results suggest that targeting the p53 R175H mutation might shrink tumors in patients with this genetic change. This targeted method could be more effective and have fewer side effects. However, further research is needed to confirm its efficacy. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic solid tumors that have the p53 R175H mutation and no standard therapy options left. They must be over 18, HLA-A*02:01 positive, in good physical condition (ECOG 0-1), able to follow study rules, and provide consent.

Inclusion Criteria

I am HLA-A*02:01 positive.

My blood, kidney, and liver functions are all within normal ranges.

I am willing and able to sign a consent form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Dose Escalation

Dose escalation of CLSP-1025 to determine the recommended dose(s) for expansion

28 days

Multiple visits for dose administration and monitoring

Monotherapy Dose Expansion

Dose expansion of CLSP-1025 to explore preliminary antitumor activity and further characterize safety and pharmacokinetics

Up to 24 months

Regular visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• CLSP-1025

Trial Overview The trial is testing CLSP-1025, a new type of treatment aimed at cancers with a specific genetic change (p53 R175H). It's an early-phase study to find out the right dose and see how well it works on various solid tumors.

How Is the Trial Designed?

Group I: Part B: Monotherapy Dose Expansion of CLSP-1025 Experimental Treatment 1 Intervention

Dose expansion of CLSP-1025 in HLA-A\*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation

Group II: Part A: Monotherapy Dose Escalation of CLSP-1025 Experimental Treatment 1 Intervention

Dose escalation of CLSP-1025 in HLA-A\*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation

Who Is Running the Clinical Trial?

Clasp Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

90+

Published Research Related to This Trial

In a clinical study involving 21 patients with various hematopoietic malignancies, KM 2210 showed a 47% overall response rate, with complete responses in 2 cases of chronic lymphocytic leukemia (CLL) and partial responses in 6 cases across different types of leukemia and lymphoma.

The treatment was generally well tolerated, with mild side effects such as breast pain and genital bleeding, but no severe toxicity to the heart, liver, or kidneys, indicating a favorable safety profile for KM 2210.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical trial of bestrabucil (KM 2210) on hematopoietic malignancies]. Nishikawa, M., Uemura, Y., Matsuoka, N., et al.[2013]

The review focused on both approved and emerging therapies for chronic lymphocytic leukemia (CLL), highlighting their mechanisms of action and efficacy in treating the disease.

It also addressed the management of adverse events related to these therapies, emphasizing the importance of safety in treatment strategies for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Outcomes for Patients With Chronic Lymphocytic Leukemia. Shadman, M., Goodrich, A.[2021]

Bendamustine monotherapy demonstrated a 60% overall response rate in 10 patients with chronic lymphocytic leukemia (CLL), indicating significant efficacy for those who could not receive fludarabine treatment.

The treatment was well-tolerated, with no disease progression or mortality during follow-up, although adverse events were common, particularly hematologic issues like lymphopenia and neutropenia, affecting all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, single-arm, Phase II clinical trial of bendamustine monotherapy in patients with chronic lymphocytic leukemia in Japan. Ogawa, Y., Izutsu, K., Kiguchi, T., et al.[2022]

Acalabrutinib, a Bruton's tyrosine kinase inhibitor, has been shown to be effective and safe for treating chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with significant improvements in efficacy observed in both monotherapy and combination treatments.

In clinical studies, acalabrutinib demonstrated a high rate of molecular remission when combined with venetoclax, while maintaining an acceptable safety profile, although some adverse events occurred in over 20% of patients, including myelosuppression and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia. Egyed, M., Lueff, S., Borbely, J., et al.[2022]

In a phase I/II study involving 13 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), the Akt inhibitor MK-2206 was safely combined with bendamustine and rituximab, achieving a maximum tolerated dose of 90 mg weekly.

The treatment combination resulted in a high overall response rate of 92%, with a median progression-free survival of 16 months and 38% of patients achieving complete remission, suggesting that this approach is a promising option for CLL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Akt inhibitor MK-2206 in combination with bendamustine and rituximab in relapsed or refractory chronic lymphocytic leukemia: Results from the N1087 alliance study. Larsen, JT., Shanafelt, TD., Leis, JF., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06778863

A Study of CLSP-1025 in Adult Patients With Solid Tumors ... This Phase 1, open-label, multicenter study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary ...

2. clasptx.com clasptx.com/press-release-publications/presentation-clsp-1025-a-novel-bispecific-t-cell-engager-targeting-the-p53r175h-mutant-peptide-presented-by-hla-a02011-wee24-bz85x

CLSP-1025 targets the most common p53 mutation ... CLSP-1025 is designed to target the p53 R175H peptide in the context of HLA-A*02:01. Enrolled patients must be HLA-A*02:01 positive and have an ...

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06778863

A Study of CLSP-1025 in Adult Patients With Solid Tumors ... This Phase 1, open-label, multicenter study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary ...

4. tempus.com tempus.com/publications/clsp-1025-a-first-in-class-precision-t-cell-engager-for-the-treatment-of-p53-mutant-cancers/?srsltid=AfmBOorA8OzqyfRUmt8AriO6X18_RL-672xScR4I62HyNfUYEIgm1iAF

CLSP-1025, a First-in-Class Precision T Cell Engager for ... CLSP-1025 leverages this specificity by targeting tumors that express the p53 R175H mutant protein in HLA-A*02:01 positive patients. The ...

5. businesswire.com businesswire.com/news/home/20250428515244/en/Clasp-Therapeutics-Doses-First-Patient-in-Phase-1-Clinical-Trial-With-a-First-in-Class-T-Cell-Engager-Designed-to-Target-Cancer-Cells-With-Absolute-Specificity

Clasp Therapeutics Doses First Patient in Phase 1 Clinical ... CLSP-1025 is designed to target the p53R175H peptide in the context of HLA-A*02:01. Enrolled patients must be HLA-A*02:01 positive and have an ...

6. clasptx.com clasptx.com/press-release-publications/presentation-clsp-1025-a-novel-bispecific-t-cell-engager-targeting-the-p53r175h-mutant-peptide-presented-by-hla-a02011-wee24

CLSP-1025, Clasp's first-in-class T-cell engager ... This study is assessing the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of CLSP-1025 in HLA-A*02:01–positive ...

7. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/1126/755024/Abstract-1126-CLSP-1025-a-first-in-class-precision

Abstract 1126: CLSP-1025, a first-in-class precision T cell ... CLSP-1025 is a half-life extended single-chain diabody IgG4 Fc fusion protein that binds to the p53(R175H)168-176 peptide presented by HLA-A*02: ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)02487-1/abstract

998TiP GUARDIAN-101: A first in human, tumor agnostic ... CLSP-1025 is the first clinical stage TCE targeting an oncogenic driver mutation. Designed to treat tumors driven by the most common p53 mutation, R175H, and ...

9. ctv.veeva.com ctv.veeva.com/study/a-phase-1-study-of-clsp-1025-in-adult-patients-with-solid-tumors-that-harbor-the-p53-r175h-mutation

A Study of CLSP-1025 in Adult Patients With Solid Tumors ... This Phase 1, open-label, multicenter study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary ...