Clinical Trials /

Safety and Efficacy Study Of CFI-402411 in Subjects With Advanced Solid Malignancies

NCT04521413

Description:

The purpose of this study is to test the safety of an investigational drug called CFI-402411 alone and in combination with pembrolizumab and to study its effects in patients with advanced solid tumors who have progressed following previous therapies.

Related Conditions:
  • Anal Canal Squamous Cell Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Cutaneous Melanoma
  • Endometrial Carcinoma
  • Esophagogastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Merkel Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Skin Squamous Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Study Of CFI-402411 in Subjects With Advanced Solid Malignancies
  • Official Title: A First-In-Human, Phase 1/2 Study Of CFI-402411, a Hematopoietic Progenitor Kinase-1 (HPK1) Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: TWT-101
  • NCT ID: NCT04521413

Conditions

  • Advanced Solid Malignancies

Interventions

DrugSynonymsArms
CFI-4024112411, 402411A1: Monotherapy Escalation
PembrolizumabKeytruda, pembroB1: Combination Escalation

Purpose

The purpose of this study is to test the safety of an investigational drug called CFI-402411 alone and in combination with pembrolizumab and to study its effects in patients with advanced solid tumors who have progressed following previous therapies.

Detailed Description

      This study will be a first-in-human study evaluating the safety and tolerability of
      CFI-402411 in subjects with advanced solid malignancies, when CFI-402411 is administered as a
      single agent or in combination with pembrolizumab. CFI-402411 is an oral pill that blocks the
      function of HPK1. Blocking HPK1 could stimulate an immune response against the tumor in
      patients. This immune response could be further enhanced when combined with pembrolizumab.
      The data obtained from this study will determine the dose and schedule and subject selection
      for further clinical studies.

      Pre-clinical findings support further development of CFI-402411 as a novel anti-cancer agent,
      and the combination of CFI-402411 with pembrolizumab as a potential strategy to improve
      outcomes of subjects with advanced malignancies.
    

Trial Arms

NameTypeDescriptionInterventions
A1: Monotherapy EscalationExperimentalDose escalation arm with CFI-402411. CFI-402411 is administered orally once daily.
  • CFI-402411
A2: Monotherapy BiomarkerExperimentalDose escalation biomarker arm with CFI-402411. CFI-402411 is administered orally once daily.
  • CFI-402411
A3: Monotherapy ExpansionExperimentalDose expansion arm with CFI-402411 at its recommended phase 2 dose.
  • CFI-402411
B1: Combination EscalationExperimentalDose escalation arm with CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).
  • CFI-402411
  • Pembrolizumab
B2: Combination ExpansionExperimentalDose expansion arm with the recommended phase 2 dose of CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).
  • CFI-402411
  • Pembrolizumab

Eligibility Criteria

        Key Inclusion Criteria: Study-Wide Eligibility (Across All Study Parts):

          1. Age > 18 years old

          2. Have progressed after ≥ 1, but no more than 3 regimens of systemic therapies for
             recurrent / metastatic disease.

          3. Subjects must have measurable disease.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

        Part A1: Monotherapy Dose Escalation Inclusion Criteria

        1. Histological or cytological confirmation of advanced solid malignancy that is refractory
        to or not a candidate for current standard treatment(s) and for whom no standard therapy is
        available.

        Part A2: Biomarker-Focused Monotherapy Backfills Inclusion Criteria

          1. Histological or cytological confirmation of one of the advanced cancers listed below;

               -  NSCLC

               -  SCLC

               -  cutaneous melanoma

               -  Merkel cell carcinoma

               -  squamous cell carcinoma of head and neck, anal canal, or skin

               -  urothelial cancer

               -  clear cell or non-clear cell renal cell carcinoma

               -  triple negative breast cancer

               -  endometrial cancer (regardless of MSI status)

               -  cervical cancer

               -  gastroesophageal cancer

               -  hepatocellular cancer

               -  any histology if known to be microsatellite-instability high (MSI-H)

          2. Tumors must be refractory to or not a candidate for current standard treatment(s) and
             for whom no standard therapy exists.

        Part A3: Monotherapy Expansion Inclusion Criteria

          1. Histological or cytological confirmation of one of the advanced cancers listed below;

               -  NSCLC cancer any histology

               -  SCLC

               -  cutaneous melanoma

               -  Merkel cell carcinoma

               -  squamous cell carcinoma of head and neck, anal canal, or skin

               -  urothelial cancer

               -  clear cell or non-clear cell renal cell carcinoma

               -  triple negative breast cancer

               -  endometrial cancer (regardless of MSI status)

               -  cervical cancer

               -  gastroesophageal cancer

               -  hepatocellular

               -  any histology if known to be microsatellite-instability high (MSI-H)

          2. Tumors must be refractory to or subjects intolerant of current standard treatment(s)
             and for whom no standard therapies are available.

          3. Optional biopsies: Subjects that consent to optional fresh tumor biopsies must have at
             least one non-target soft tissue tumor lesion that can be biopsied.

        Part B1: CFI-402411 in Combination with Pembrolizumab Dose Escalation Inclusion Criteria

          1. Subjects must be deemed eligible by the Investigator to receive pembrolizumab.

          2. Histological or cytological confirmation of one of the advanced cancers listed below
             (list may vary in each country, USA shown here);

               -  NSCLC cancer any histology

               -  SCLC

               -  cutaneous melanoma

               -  Merkel cell carcinoma

               -  squamous cell carcinoma of head and neck, anal canal, or skin

               -  urothelial cancer

               -  clear cell or non-clear cell renal cell carcinoma

               -  triple negative breast cancer

               -  endometrial cancer (regardless of MSI status)

               -  cervical cancer

               -  gastroesophageal cancer

               -  hepatocellular cancer

               -  any histology if known to be microsatellite-instability high (MSI-H)

        Tumors must be refractory to or subjects intolerant of current standard treatment(s) or for
        whom no standard therapy is available.

        Part B2: CFI-402411 in Combination with Pembrolizumab Expansion Inclusion Criteria

          1. Subjects must be deemed eligible by the Investigator to receive pembrolizumab

          2. Histological or cytological confirmation of one of the advanced cancers listed below
             (list may vary in each country, USA shown here);

               -  non-small cell lung cancer any histology

               -  SCLC

               -  cutaneous melanoma

               -  Merkel Cell carcinoma

               -  squamous cell carcinoma of head and neck, anal canal, or skin

               -  urothelial cancer

               -  clear cell or non-clear cell renal cell carcinoma

               -  triple negative breast cancer

               -  endometrial cancer (regardless of MSI status)

               -  gastroesophageal cancer

               -  hepatocellular cancer

               -  any histology if known to be microsatellite-instability high (MSI-H)

          3. Tumors must be refractory to or subjects intolerant of current standard non-IO
             treatment(s) or for whom no standard therapy is available.

        Key Exclusion Criteria: Study-Wide Eligibility (Across All Study Parts)

        Subjects will be excluded from the study if any of the following criteria is met;

          1. Previous treatment with an HPK1 inhibitor in other clinical trials.

          2. Diagnosis of autoimmune-based disease or clinically significant auto-immune disorders.

          3. Have symptomatic congestive heart failure, active angina pectoris or recent myocardial
             infarction (within 6 mos).

          4. Have chronic atrial fibrillation.

          5. Known central nervous system metastasis.

          6. Stroke or transient ischemic attack, or other ischemic events or thromboembolic events
             within 3 months of study enrollment.

          7. A history of QTc prolongation or a marked baseline prolongation of QT/QTc interval or
             a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family
             history of Long QT Syndrome).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To assess the incidence of adverse events of CFI-402411 as a single agent and at the recommended phase 2 dose (RP2D).
Time Frame:48 months
Safety Issue:
Description:The number of subjects who experience an adverse event that was possibly related to study drug.

Secondary Outcome Measures

Measure:To identify the maximum tolerated dose of single agent CFI-402411 alone and in combination with pembrolizumab.
Time Frame:48 months
Safety Issue:
Description:Safety tables and pharmacokinetic tables will be assessed.
Measure:To further assess the incidence of adverse events of CFI-402411.
Time Frame:48 months
Safety Issue:
Description:The number of subjects who experience an adverse event that was possibly related to study drug.
Measure:To assess best overall response of CFI-402411 monotherapy and in combination with pembrolizumab.
Time Frame:48 months
Safety Issue:
Description:Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category.
Measure:To assess overall response rates of CFI-402411 monotherapy and in combination with pembrolizumab.
Time Frame:48 months
Safety Issue:
Description:For all subjects the overall response rates of complete response and partial response will be calculated and summarized by dose cohort and overall.
Measure:To assess overall survival of CFI-402411 monotherapy and in combination with pembrolizumab.
Time Frame:48 months
Safety Issue:
Description:The time from first dose until the date of death from any cause will be calculated and summarized for all patients by dose cohort and overall.
Measure:To assess progression free survival of CFI-402411 monotherapy and in combination with pembrolizumab.
Time Frame:48 months
Safety Issue:
Description:Time from first dose to disease progression or death whichever occurs first will be calculated and summarized for all patients by dose cohort and overall.
Measure:To assess duration of response of CFI-402411 monotherapy and in combination with pembrolizumab.
Time Frame:48 months
Safety Issue:
Description:The time from the first objective response to the time of documented disease progression or death due to any cause, whichever occurs first, will be calculated and summarized for all patients by dose cohort and overall.
Measure:To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through AUC.
Time Frame:48 months
Safety Issue:
Description:Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.
Measure:To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Cmax.
Time Frame:48 months
Safety Issue:
Description:Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax tabulated by dose group.
Measure:To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Tmax.
Time Frame:48 months
Safety Issue:
Description:Tmax will be assessed by the time to achieve maximum plasma concentration and will be tabulated by dose group.
Measure:To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab though Cmin.
Time Frame:48 months
Safety Issue:
Description:Cmin will be calculated through the measured pre-dose plasma concentration and tabulated by dose group.
Measure:To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through T1/2.
Time Frame:48 months
Safety Issue:
Description:Elimination half life will be calculated and tabulated by dose group.
Measure:To evaluate the effect of CFI-402411 treatment on immune- or disease related biomarkers.
Time Frame:48 months
Safety Issue:
Description:The effects of CFI-402411 on pharmacodynamic biomarkers (cytokine levels) will be assessed by percent changes from baseline.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Treadwell Therapeutics, Inc

Trial Keywords

  • advanced tumors
  • pembro
  • keytruda
  • pembrolizumab
  • 2411
  • CFI-402411
  • first in human
  • first-in-human
  • hematopoietic progenitor kinase-1 inhibitor
  • HPK1
  • advanced solid malignancies
  • solid malignancies
  • TWT-101
  • TWT101
  • UHN
  • University Health Network
  • Treadwell Therapeutics

Last Updated

August 19, 2020