Clinical Trials /

Talabostat and Pembrolizumab for the Treatment of Advanced Solid Cancers

NCT04171219

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Talabostat and Pembrolizumab for the Treatment of Advanced Solid Cancers
  • Official Title: A Phase 2 Basket Study of BXCL701, a Small Molecule Inhibitor of Dipeptidyl Peptidases (DPP), Administered in Combination With Pembrolizumab in Patients With Advanced Solid Cancers

Clinical Trial IDs

  • ORG STUDY ID: 2019-0748
  • SECONDARY ID: NCI-2019-07569
  • SECONDARY ID: 2019-0748
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04171219

Conditions

  • Advanced Malignant Solid Neoplasm
  • Recurrent Malignant Solid Neoplasm

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (talabostat, pembrolizumab)
TalabostatBXCL 701, BXCL-701, BXCL701, PT-100Treatment (talabostat, pembrolizumab)
Talabostat MesylateVal-boro-ProTreatment (talabostat, pembrolizumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and
      immune (i)RECIST in patients treated in cohort A and in patients treated in cohort B.

      II. To evaluate dose-limiting toxicities (DLT) in the first 6 patients enrolled to the study.

      SECONDARY OBJECTIVES:

      I. To evaluate progression-free survival (PFS). II. To evaluate duration of response (DOR).
      III. To evaluate overall survival (OS). IV. To evaluate overall safety and tolerability.

      EXPLORATORY OBJECTIVES:

      I. To evaluate the quantitative and qualitative effects of talabostat (BXCL701) in
      combination with pembrolizumab on relevant immune effector cytokines in blood.

      II. To evaluate the quantitative and qualitative effects of BXCL701 in combination with
      pembrolizumab on various immunological effector cells, including neutrophils, myeloid derived
      suppressor cells (MDSCs), dendritic cells, cancer associated fibroblast (CAF), T-cells and
      macrophage density in pre-dose tumor biopsies and when feasible in post-dose tumor tissues.

      III. To explore the predictive value of baseline programmed death ligand 1 (PD-L1) tumor
      expression and tumor mutation burden (TMB) with clinical outcomes.

      IV. To evaluate changes in serially collected blood circulating tumor deoxyribonucleic acid
      (DNA) (ctDNA) to assess for tumor response and clonal evolution.

      V. To evaluate pre- and post-treatment PD-L1 positron emission tomography (PET)/computed
      tomography (CT) as a predictive tool for therapeutic efficacy.

      OUTLINE:

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

      After completion of study treatment, patients are followed up at 30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (talabostat, pembrolizumab)ExperimentalPatients receive talabostat PO 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.
  • Pembrolizumab
  • Talabostat
  • Talabostat Mesylate

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  Platelet count >= 75 x 10^9/L

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
             [HCG]) within 14 days prior to the initiation of treatment and/or postmenopausal women
             must be amenorrhoeic for at least 12 months to be considered of non-childbearing
             potential. Women of childbearing potential must agree and commit to the use of 2
             highly effective methods of birth control throughout the duration of the study until
             at least 4 months following the last dose of study drug. Acceptable methods are
             defined as those that result, alone or in combination, in a low failure rate (ie, less
             than 1% per year) when used consistently and correctly, such as surgical
             sterilization, an intrauterine device, or hormonal contraception in combination with a
             barrier method. It is currently unknown whether BXCL701 or pembrolizumab may reduce
             the effectiveness of systemically acting hormonal contraceptives; therefore, women
             using systemically acting hormonal contraceptives should add a barrier method. In
             certain countries (if permitted by law), WOCBP may agree to abide by heterosexual
             sexual abstinence during the time of participation in this study

          -  Male patients and their female partners of childbearing potential must agree and
             commit to use a barrier contraception (eg, condom with spermicidal
             foam/gel/film/cream/suppository) throughout the duration of the study until at least
             60 days following the last dose of study drug, in addition to their female partners
             using either an intrauterine device or hormonal contraception and continuing until at
             least 4 months days following the last dose of study drug. This criterion may be
             waived for male patients who have had a vasectomy > 6 months before signing the
             informed consent form (ICF)

          -  Patient has signed informed consent prior to initiation of any study-specific
             procedures or treatment

          -  Patient is able to adhere to the study visit schedule and other protocol requirements

        Exclusion Criteria:

          -  Patient cannot swallow oral medication

          -  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 treatment with an investigational systemic anticancer agent
             within 14 days prior to study drug administration

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:Up to 2.5 years
Safety Issue:
Description:Evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) and immune (i)RECIST.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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