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

NCT ID: NCT04521413

Last Updated: 2025-05-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-31
• Study Completion Date: 2025-12-31

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.

Conditions

Advanced Solid Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A1: Monotherapy Escalation

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

Group Type: EXPERIMENTAL

CFI-402411

Intervention Type: DRUG

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.

A2: Monotherapy Biomarker

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

Group Type: EXPERIMENTAL

CFI-402411

Intervention Type: DRUG

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.

A3: Monotherapy Expansion

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

Group Type: EXPERIMENTAL

CFI-402411

Intervention Type: DRUG

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.

B1: Combination Escalation

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

Group Type: EXPERIMENTAL

CFI-402411

Intervention Type: DRUG

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.

Pembrolizumab

Intervention Type: DRUG

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

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).

Group Type: EXPERIMENTAL

CFI-402411

Intervention Type: DRUG

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.

Pembrolizumab

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

2411; 402411; Keytruda; pembro

Eligibility Criteria

Inclusion Criteria

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

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.

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.

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.

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.

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.

Exclusion Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TIO Discovery Engine

UNKNOWN

Sponsor Role: collaborator

Treadwell Therapeutics, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Omid Hamid, Dr

Role: PRINCIPAL_INVESTIGATOR

The Angeles Clinic, Los Angeles

Locations

University of California San Diego

La Jolla, California, United States

The Angeles Clinic

Los Angeles, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

Florida Cancer Specialists

Sarasota, Florida, United States

START - Mid-West

Grand Rapids, Michigan, United States

SCRI - Nashville

Nashville, Tennessee, United States

MD Anderson

Houston, Texas, United States

START - San Antonio

San Antonio, Texas, United States

Virginia Cancer Specialist

Fairfax, Virginia, United States

Cross Cancer Institute

Edmonton, Alberta, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Prince of Wales Hospital

Shatin, , Hong Kong

Countries

United States; Canada; Hong Kong

Other Identifiers

TWT-101

Identifier Type: -

Identifier Source: org_study_id