CLSP-1025 for Cancer

(GUARDIAN-101 Trial)

Recruiting at 5 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

Trial Summary

What is the purpose of this trial?

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.

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.

What safety data exists for the treatment CLSP-1025 or similar treatments?

The treatment MK-2206, similar to CLSP-1025, was tested in combination with other drugs for chronic lymphocytic leukemia and showed some side effects like low white blood cell counts, fever, rash, and diarrhea. Another treatment, KM 2210, showed mild side effects like breast pain and appetite loss, but no serious heart, liver, or kidney issues. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

A multicenter, single-arm, Phase II clinical trial of bendamustine monotherapy in patients with chronic lymphocytic leukemia in Japan. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

[Clinical trial of bestrabucil (KM 2210) on hematopoietic malignancies]. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Improving Outcomes for Patients With Chronic Lymphocytic Leukemia. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia. [2022]