Talabostat and Pembrolizumab for the Treatment of Advanced Solid Cancers

NCT04171219 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2019-0748NCI-2019-07569
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects of talabostat and pembrolizumab and to see how well they work for the treatment of solid cancers that have spread to other places in the body (advanced). Talabostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving talabostat and pembrolizumab may help control the disease.

Conditions

Advanced Malignant Solid Neoplasm; Recurrent Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (3)

• Disease Control Rate Per RECIST v1.1

  Disease control rate was defined as the percentage of patients who had complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1.

  At baseline and at the end of Cycle 3 (approximately 9 weeks after the first study treatment dose), and then approximately every 9 weeks thereafter until development of progressive disease, up to 3 years

• Immune-related Disease Control Rate Per iRECIST

  Immune-related disease control rate was defined as the percentage of patients who had immune-related complete response (iCR), immune-related partial response (iPR), or immune-related stable disease (iSD) according to iRECIST.

  At baseline and at the end of Cycle 3 (approximately 9 weeks after the first study treatment dose), and then approximately every 9 weeks thereafter until development of progressive disease, up to 3 years

• Dose-limiting Toxicities (DLTs)

  A DLT was defined as any of the following AEs occurring during Cycle 1, regardless of investigator attribution to study treatment: * Any Grade 4 laboratory abnormality, regardless of duration. * Any Grade 3 laboratory abnormalities if associated with clinical symptoms regardless of duration * Any Grade ≥3 non-hematologic AE, with the exceptions of Grade ≥3 nausea, vomiting, diarrhea, constipation, and fatigue, that resolves to Grade ≤1 within 72 hours with optimal medical management and/or supportive measures. * Grade ≥3 thrombocytopenia with Grade \>1 bleeding or requirement for platelet transfusion. * Grade ≥3 febrile neutropenia. * Grade ≥3 fever. * Grade ≥3 skin rash. * AST or ALT \>3 × upper limit of normal \[ULN\] with concomitant total bilirubin \>2 × ULN. * Any toxicity resulting in ≥30% held/skipped doses of BXCL701 during Cycle 1. * Delay of Cycle 2 by ≥14 days due to toxicity. * Any other significant toxicity considered by the investigatoro be dose-limiting.

  DLT was assessed during Cycle 1 (21-day cycle)

Secondary Outcomes (4)

• Progression-free Survival (PFS) by RECIST v1.1

  At baseline and at the end of Cycle 3 (approximately 9 weeks after the first study treatment dose), and then approximately every 9 weeks thereafter until development of progressive disease, up to 3 years

• Progression-free Survival (PFS) by iRECIST

  At baseline and at the end of Cycle 3 (approximately 9 weeks after the first study treatment dose), and then approximately every 9 weeks thereafter until development of progressive disease, up to 3 years

• Overall Survival (OS)

  From the first date of administration of the study drug to the date of data cut-off (January 7, 2024)

• Treatment-related Adverse Event (TRAE)

  Patients were monitored for AE from the first day of administration of study medication through 30 days following the last dose of BXCL701 and or pembrolizumab, an average of 3 years.

Study Arms (1)

Treatment (talabostat, pembrolizumab)

EXPERIMENTAL

Patients receive talabostat PO BID on days 1-14 and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab; Drug: Talabostat Mesylate

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (talabostat, pembrolizumab)

Talabostat Mesylate DRUG

Given PO

Also known as: Val-boro-Pro

Treatment (talabostat, pembrolizumab)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with a histology or cytology proven solid advanced cancer, which failed or is intolerant of standard therapies known to offer survival benefit unless standard therapies include PD1 or PD-L1 antibodies
• Lead-in stage: patient with advanced cancers meeting the criteria above with or without prior treatment with PD1/PDL1 antibodies. Patients with prior treatment with PD1/PDL1 antibodies should be relapsed
• Efficacy stage cohort A: patients with advanced cancers not previously treated with PD1/PDL1 antibodies
• Efficacy stage cohort B: patients with advanced cancers which have relapsed or progressed with PD1/PDL1 antibodies
• Patient with a life expectancy of more than 3 months, in the opinion of the investigator
• Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 2
• Patients \< 18 years of age have to weigh \> 40 kgs
• Patients must have measurable disease by RECIST 1.1 and iRECIST. Disease amenable to a biopsy is not mandatory
• Patient's acute toxic effects of previous anticancer therapy have resolved to =\< grade 1 except for grade 2 peripheral neuropathy or any grade of alopecia
• Serum creatinine =\< 1.5 times institutional upper limit of normal (ULN) or calculated creatinine clearance \> 40 mL/min
• Serum albumin \>= 2.5 g/dL
• Total bilirubin =\< 1.5 x ULN (for patients with known Gilbert syndrome \< 3 x ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN (patients with hepatic metastases must have AST/ALT =\< 5 x ULN)
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
• Hemoglobin \>= 8 g/dL and no red blood cell transfusions during the prior 7 days

You may not qualify if:

• Patient cannot swallow oral medication
• Patient is on gliptins
• Patient has active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy (patient must be off steroids). Patients with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by brain magnetic resonance imaging/computed tomography (MRI/CT)
• Patient has received external-beam radiation or another systemic anticancer therapy within 14 days or 5 half-lives, whichever is shorter, prior to study treatment
• Patient has received treatment with an investigational systemic anticancer agent within 14 days prior to study drug administration
• Patient has an additional active malignancy that may confound the assessment of the study endpoints. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer and carcinoma in situ (including transitional cell carcinoma, anal carcinoma, and melanoma in situ). Patients with simultaneous cancers, which are not active and do not require treatment may be eligible contingent on discussion with the principle investigator (PI) and supporter
• Patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
• Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a prednisone equivalent dose of \> 10 mg daily for at least 1 week or other form of immunosuppressive therapy within 7 days prior to cycle 1 day 1 (C1D1)
• Patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements
• Patient has known positive status for human immunodeficiency virus active or chronic hepatitis B or hepatitis C. Patients with history of hepatitis B or C and undetectable viral load are eligible. Screening is not required
• Has a clinically significant upper gastrointestinal obstruction, abnormal physiological function or malabsorption syndrome that may affect the absorption of the study medication
• Patient has any medical condition which, in the opinion of the investigator, places the patient at an unacceptably high risk for toxicity
• Patient is pregnant or breast-feeding

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

pembrolizumab; PT-100 dipeptide

Results Point of Contact

• Title: Aung Naing, MD
• Organization: M.D. Anderson Cancer Center

anaing@mdanderson.org

713-563-3885

Study Officials

• Aung Naing, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 20, 2019
• Study Start: March 19, 2020
• Primary Completion: March 11, 2025
• Study Completion: March 11, 2025
• Last Updated: May 16, 2025
• Results First Posted: May 16, 2025

Record last verified: 2025-05

Locations

US (1)