NCT04521413

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.

Trial Health

58
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
170

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Aug 2020

Longer than P75 for phase_1

Geographic Reach
3 countries

13 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 31, 2020

Completed
20 days until next milestone

First Posted

Study publicly available on registry

August 20, 2020

Completed
11 days until next milestone

Study Start

First participant enrolled

August 31, 2020

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2025

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2025

Completed
Last Updated

May 21, 2025

Status Verified

September 1, 2024

Enrollment Period

5.2 years

First QC Date

July 31, 2020

Last Update Submit

May 16, 2025

Conditions

Keywords

advanced tumorspembrokeytrudapembrolizumab2411CFI-402411first in humanfirst-in-humanhematopoietic progenitor kinase-1 inhibitorHPK1advanced solid malignanciessolid malignanciesTWT-101TWT101UHNUniversity Health NetworkTreadwell Therapeutics

Outcome Measures

Primary Outcomes (4)

  • To assess the incidence of adverse events of CFI-402411 as a single agent and at the recommended phase 2 dose (RP2D).

    The number of subjects who experience an adverse event that was possibly related to study drug.

    48 months

  • To assess the incidence of adverse events with CFI-402411 in combination with pembrolizumab and at the RP2D.

    The number of subjects who experience an adverse event that was possibly related to study drug.

    48 months

  • To examine best overall response rate in subjects treated at multiple dose levels of CFI-402411.

    Best overall response rate will be summarized by dose cohort and overall using the percent of patients in each tumor response category.

    48 months

  • To examine progression free survival in subjects treated at multiple dose levels of CFI-402411.

    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.

    48 months

Secondary Outcomes (13)

  • To identify the maximum tolerated dose of single agent CFI-402411 alone and in combination with pembrolizumab.

    48 months

  • To further assess the incidence of adverse events of CFI-402411.

    48 months

  • To assess best overall response of CFI-402411 monotherapy and in combination with pembrolizumab.

    48 months

  • To assess overall response rates of CFI-402411 monotherapy and in combination with pembrolizumab.

    48 months

  • To assess overall survival of CFI-402411 monotherapy and in combination with pembrolizumab.

    48 months

  • +8 more secondary outcomes

Study Arms (5)

A1: Monotherapy Escalation

EXPERIMENTAL

Dose escalation arm with CFI-402411. CFI-402411 is administered orally once daily.

Drug: CFI-402411

A2: Monotherapy Biomarker

EXPERIMENTAL

Dose escalation biomarker arm with CFI-402411. CFI-402411 is administered orally once daily.

Drug: CFI-402411

A3: Monotherapy Expansion

EXPERIMENTAL

Dose expansion arm with CFI-402411 at its recommended phase 2 dose.

Drug: CFI-402411

B1: Combination Escalation

EXPERIMENTAL

Dose escalation arm with CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).

Drug: CFI-402411Drug: Pembrolizumab

B2: Combination Expansion

EXPERIMENTAL

Dose expansion arm with the recommended phase 2 dose of CFI-402411 in combination with pembrolizumab (at its labeled dose and schedule).

Drug: CFI-402411Drug: Pembrolizumab

Interventions

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.

Also known as: 2411, 402411
A1: Monotherapy EscalationA2: Monotherapy BiomarkerA3: Monotherapy ExpansionB1: Combination EscalationB2: Combination Expansion

Pembrolizumab will be given at its labeled dose and schedule, 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.

Also known as: Keytruda, pembro
B1: Combination EscalationB2: Combination Expansion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \> 18 years old
  • Have progressed after ≥ 1, but no more than 3 regimens of systemic therapies for recurrent / metastatic disease.
  • Subjects must have measurable disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 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.
  • 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)
  • +52 more criteria

You may not qualify if:

  • Subjects will be excluded from the study if any of the following criteria is met;
  • Previous treatment with an HPK1 inhibitor in other clinical trials.
  • Diagnosis of autoimmune-based disease or clinically significant auto-immune disorders.
  • Have symptomatic congestive heart failure, active angina pectoris or recent myocardial infarction (within 6 mos).
  • Have chronic atrial fibrillation.
  • Known central nervous system metastasis.
  • Stroke or transient ischemic attack, or other ischemic events or thromboembolic events within 3 months of study enrollment.
  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

University of California San Diego

La Jolla, California, 92093, United States

Location

The Angeles Clinic

Los Angeles, California, 90025, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

START - Mid-West

Grand Rapids, Michigan, 49546, United States

Location

SCRI - Nashville

Nashville, Tennessee, 37023, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

START - San Antonio

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialist

Fairfax, Virginia, 22031, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G1Z2, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

MeSH Terms

Interventions

pembrolizumab

Study Officials

  • Omid Hamid, Dr

    The Angeles Clinic, Los Angeles

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Dose escalation and expansion for monotherapy and combination arms with pembrolizumab
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 31, 2020

First Posted

August 20, 2020

Study Start

August 31, 2020

Primary Completion

November 1, 2025

Study Completion

December 1, 2025

Last Updated

May 21, 2025

Record last verified: 2024-09

Data Sharing

IPD Sharing
Will not share

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.

Locations