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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04521413
Recruitment Status : Recruiting
First Posted : August 20, 2020
Last Update Posted : February 6, 2023
Sponsor:
Collaborator:
TIO Discovery Engine
Information provided by (Responsible Party):
Treadwell Therapeutics, Inc

Tracking Information
First Submitted Date  ICMJE July 31, 2020
First Posted Date  ICMJE August 20, 2020
Last Update Posted Date February 6, 2023
Actual Study Start Date  ICMJE August 31, 2020
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 19, 2020)
  • 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 ]
    The number of subjects who experience an adverse event that was possibly related to study drug.
  • To assess the incidence of adverse events with CFI-402411 in combination with pembrolizumab and at the RP2D. [ Time Frame: 48 months ]
    The number of subjects who experience an adverse event that was possibly related to study drug.
  • To examine best overall response rate in subjects treated at multiple dose levels of CFI-402411. [ Time Frame: 48 months ]
    Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category.
  • To examine progression free survival in subjects treated at multiple dose levels of CFI-402411. [ Time Frame: 48 months ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 19, 2020)
  • To assess the safety of treatment with CFI-402411 as a single agent and at the recommended phase 2 dose (RP2D). [ Time Frame: 48 months ]
    The number of subjects who experience an adverse event that was possibly related to study drug.
  • To assess the safety of treatment with CFI-402411 in combination with pembrolizumab and at the RP2D. [ Time Frame: 48 months ]
    The number of subjects who experience an adverse event that was possibly related to study drug.
  • To examine best overall response rate in subjects treated at multiple dose levels of CFI-402411. [ Time Frame: 48 months ]
    Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category.
  • To examine progression free survival in subjects treated at multiple dose levels of CFI-402411. [ Time Frame: 48 months ]
    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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2020)
  • To identify the maximum tolerated dose of single agent CFI-402411 alone and in combination with pembrolizumab. [ Time Frame: 48 months ]
    Safety tables and pharmacokinetic tables will be assessed.
  • To further assess the incidence of adverse events of CFI-402411. [ Time Frame: 48 months ]
    The number of subjects who experience an adverse event that was possibly related to study drug.
  • To assess best overall response of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category.
  • To assess overall response rates of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    For all subjects the overall response rates of complete response and partial response will be calculated and summarized by dose cohort and overall.
  • To assess overall survival of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    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.
  • To assess progression free survival of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    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.
  • To assess duration of response of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    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.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through AUC. [ Time Frame: 48 months ]
    Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Cmax. [ Time Frame: 48 months ]
    Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax tabulated by dose group.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Tmax. [ Time Frame: 48 months ]
    Tmax will be assessed by the time to achieve maximum plasma concentration and will be tabulated by dose group.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab though Cmin. [ Time Frame: 48 months ]
    Cmin will be calculated through the measured pre-dose plasma concentration and tabulated by dose group.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through T1/2. [ Time Frame: 48 months ]
    Elimination half life will be calculated and tabulated by dose group.
  • To evaluate the effect of CFI-402411 treatment on immune- or disease related biomarkers. [ Time Frame: 48 months ]
    The effects of CFI-402411 on pharmacodynamic biomarkers (cytokine levels) will be assessed by percent changes from baseline.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2020)
  • To identify the maximum tolerated dose of single agent CFI-402411 alone and in combination with pembrolizumab. [ Time Frame: 48 months ]
    Safety tables and pharmacokinetic tables will be assessed.
  • To further assess the safety of treatment with CFI-402411. [ Time Frame: 48 months ]
    The number of subjects who experience an adverse event that was possibly related to study drug.
  • To assess best overall response of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category.
  • To assess overall response rates of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    For all subjects the overall response rates of complete response and partial response will be calculated and summarized by dose cohort and overall.
  • To assess overall survival of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    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.
  • To assess progression free survival of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    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.
  • To assess duration of response of CFI-402411 monotherapy and in combination with pembrolizumab. [ Time Frame: 48 months ]
    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.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through AUC. [ Time Frame: 48 months ]
    Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Cmax. [ Time Frame: 48 months ]
    Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax tabulated by dose group.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through Tmax. [ Time Frame: 48 months ]
    Tmax will be assessed by the time to achieve maximum plasma concentration and will be tabulated by dose group.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab though Cmin. [ Time Frame: 48 months ]
    Cmin will be calculated through the measured pre-dose plasma concentration and tabulated by dose group.
  • To assess the pharmacokinetic profile of CFI-402411 alone when it is administered in combination with pembrolizumab through T1/2. [ Time Frame: 48 months ]
    Elimination half life will be calculated and tabulated by dose group.
  • To evaluate the effect of CFI-402411 treatment on immune- or disease related biomarkers. [ Time Frame: 48 months ]
    The effects of CFI-402411 on pharmacodynamic biomarkers (cytokine levels) will be assessed by percent changes from baseline.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of CFI-402411 in Subjects With Advanced Solid Malignancies
Official Title  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Dose escalation and expansion for monotherapy and combination arms with pembrolizumab
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Malignancies
Intervention  ICMJE
  • Drug: CFI-402411
    CFI-402411 is administered orally once daily. The starting dose is 80 mg/day for escalation arms and the recommended dose for the expansion arms.
    Other Names:
    • 2411
    • 402411
  • Drug: Pembrolizumab
    Pembrolizumab will be given at its labeled dose and schedule, 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.
    Other Names:
    • Keytruda
    • pembro
Study Arms  ICMJE
  • Experimental: A1: Monotherapy Escalation
    Dose escalation arm with CFI-402411. CFI-402411 is administered orally once daily.
    Intervention: Drug: CFI-402411
  • Experimental: A2: Monotherapy Biomarker
    Dose escalation biomarker arm with CFI-402411. CFI-402411 is administered orally once daily.
    Intervention: Drug: CFI-402411
  • Experimental: A3: Monotherapy Expansion
    Dose expansion arm with CFI-402411 at its recommended phase 2 dose.
    Intervention: Drug: CFI-402411
  • Experimental: B1: Combination Escalation
    Dose escalation arm with CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).
    Interventions:
    • Drug: CFI-402411
    • Drug: Pembrolizumab
  • Experimental: B2: Combination Expansion
    Dose expansion arm with the recommended phase 2 dose of CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).
    Interventions:
    • Drug: CFI-402411
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 19, 2020)		 170
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Treadwell Therapeutics Clinical Trials +1-416-455-7510 clinicaltrials@treadwelltx.com
Listed Location Countries  ICMJE Canada,   Hong Kong,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04521413
Other Study ID Numbers  ICMJE TWT-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: It is too early to determine whether we will make IPD available - we do not yet have a process written on this. Field will be updated once our policy / process is written.
Current Responsible Party Treadwell Therapeutics, Inc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Treadwell Therapeutics, Inc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE TIO Discovery Engine
Investigators  ICMJE
Principal Investigator: Omid Hamid, Dr The Angeles Clinic, Los Angeles
PRS Account Treadwell Therapeutics, Inc
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP