Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Clasp Therapeutics, Inc.
No Placebo Group
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.
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.
12345Will 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.
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
Key
I am HLA-A*02:01 positive.
I am 18 years old or older.
My cancer has spread and gotten worse after treatment.
My tumor has a specific TP53 mutation.
I am fully active or restricted in physically strenuous activity but can do light work.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Part B: Monotherapy Dose Expansion of CLSP-1025Experimental Treatment1 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-1025Experimental Treatment1 Intervention
Dose escalation of CLSP-1025 in HLA-A\*02:01-positive adult patients with advanced solid tumors that harbor the p53 R175H mutation
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Sarah Cannon Research InstituteNashville, TN
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Who is running the clinical trial?
Clasp Therapeutics, Inc.Lead Sponsor
References
[Clinical trial of bestrabucil (KM 2210) on hematopoietic malignancies]. [2013]Twenty-one patients were entered for a clinical study of KM 2210, the benzoate of an estradiol-chlorambucil conjugate, in the treatment of hematopoietic malignancies. These included 4 cases of chronic lymphocytic leukemia (CLL), 5 cases of chronic myelogenous leukemia (CML), 5 cases of malignant lymphoma (ML) and 7 cases of multiple myeloma (MM). Twelve cases had prior chemotherapy. KM 2210 was given orally at a dose of 50-300 mg daily. Of 19 evaluable cases, two cases with CLL achieved complete response and 6 cases including 2 with CLL, 2 with CML and 3 with ML achieved partial response. There were no responders among the cases of MM. The partial and complete response rate was 47%. Toxicity included mild breast or nipple pain (28.6%), genital bleeding (9.5%), appetite loss (9.5%) and gynecomastia (4.8%). These side effects may have been due to increased levels of estrogen. Hematopoietic toxicity was mild and well tolerated. No cardiac, hepatic or renal toxicity was observed in this study. These results suggest that KM 2210 might be an effective candidate for the treatment of hematopoietic malignancies, especially CLL.
A multicenter, single-arm, Phase II clinical trial of bendamustine monotherapy in patients with chronic lymphocytic leukemia in Japan. [2022]The present study was intended to examine the efficacy and safety of bendamustine monotherapy in patients with previously untreated chronic lymphocytic leukemia (CLL) for whom treatment with fludarabine (FLU) was not suitable, and in FLU-naïve patients with relapsed/refractory CLL. We intravenously administered bendamustine 100 mg/m2/day on days 1 and 2 of each 28-day cycle to 10 patients (eight previously untreated; two relapsed/refractory) up to six cycles. The primary endpoint was overall response rate (ORR: partial remission or better) according to the 2008 International Workshop on the CLL guidelines. The ORR was 60.0% (6/10), with the 95% confidence interval of 26.2-87.8%. Neither disease progression nor mortality occurred during follow-up. Therefore, the medians for progression-free survival, duration of response, and overall survival were estimated to exceed 12.6, 8.7, and 12.6 months, respectively. Adverse events (AEs) occurred in all 10 patients. Grade 3/4 hematologic AEs included lymphopenia (90%), neutropenia (80%), CD4 lymphopenia (80%), and leukopenia (70%). Nonhematologic AEs included constipation (80%), nausea (80%), malaise (50%), and anorexia (50%). There was one case each of grade 3 infection and adenocarcinoma of the stomach. Bendamustine showed high efficacy for Japanese patients with previously untreated or relapsed/refractory CLL, and its safety profile was acceptable.
Akt inhibitor MK-2206 in combination with bendamustine and rituximab in relapsed or refractory chronic lymphocytic leukemia: Results from the N1087 alliance study. [2023]Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK-2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK-2206 in combination with BR in relapsed CLL. Single-agent MK-2206 (weekly dosed) was administered one-week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2-6. Phase II employed the MTD of MK-2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6-cycle of therapy. The maximum tolerated dose of MK-2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial.
Improving Outcomes for Patients With Chronic Lymphocytic Leukemia. [2021]Mazyar Shadman, MD, MPH, and Amy Goodrich, CRNP, reviewed data regarding the mechanistic activity, efficacy, and safety of approved and emerging therapeutic options for chronic lymphocytic leukemia (CLL) and strategies for managing adverse events associated with approved therapies for CLL.
Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia. [2022]Bruton's tyrosine kinase inhibitors have changed the treatment landscape for chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma dramatically. In 2019, acalabrutinib was approved by the US FDA for the treatment of treatment-naive and relapsed/refractory CLL and MCL. Acalabrutinib monotherapy was found to be effective and safe in CLL patients. In ASCEND and ELEVATE treatment-naive studies, acalabrutinib monotherapy and the combination with obinutuzumab demonstrated improved efficacy and an acceptable safety profile. The triple combination with venetoclax showed a high rate of molecular remission without an impaired safety profile. Adverse events, with an occurrence rate of >20%, were as follows: grade 1-2 myelosuppression, gastrointestinal toxicity, rash, constitutional symptoms; grade 3 or 4 toxicities were syncope, pneumonia, hypertension, atrial fibrillation, neutropenia and thrombocytopenia.