NCT04521413

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

Active, enrolled Phase 1/Phase 2 Last updated 16 May 2025

What this trial tests

Phase 1/Phase 2 trial testing CFI-402411 in Advanced Solid Malignancies in 170 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

31 August 2020

Primary endpoint
1 November 2025

1 December 2025

Quick facts

Lead sponsor	Treadwell Therapeutics, Inc
Phase	Phase 1/Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	170
Start date	31 August 2020
Primary completion	1 November 2025
Estimated completion	1 December 2025
Sites	13 locations across United States, Canada, Hong Kong

Drugs / interventions tested

• CFI-402411 — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Advanced Solid Malignancies — all drugs for Advanced Solid Malignancies →

Sponsor

Treadwell Therapeutics, Inc — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Malignancies. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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.

Sponsor's own 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Small-molecule agents for cancer immunotherapy.
   Wang F, Fu K, Wang Y, Pan C, et al · · 2024 · cited 41× · PMID 38486980 · DOI 10.1016/j.apsb.2023.12.010
2. Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.
   Ou X, Gao G, Habaz IA, Wang Y. · · 2024 · cited 30× · PMID 39184861 · DOI 10.1002/mco2.694
3. Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.
   Laletin V, Bernard PL, Costa da Silva C, Guittard G, et al · · 2023 · cited 27× · PMID 37217244 · DOI 10.1136/jitc-2022-005845
4. Small molecule inhibitors for cancer immunotherapy and associated biomarkers - the current status.
   Schlicher L, Green LG, Romagnani A, Renner F. · · 2023 · cited 22× · PMID 38022587 · DOI 10.3389/fimmu.2023.1297175
5. Emerging therapeutic strategies for enhancing sensitivity and countering resistance to programmed cell death protein 1 or programmed death-ligand 1 inhibitors in non-small cell lung cancer.
   Villaruz LC, Blumenschein GR, Otterson GA, Leal TA. · · 2023 · cited 10× · PMID 36848319 · DOI 10.1002/cncr.34683
6. Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis.
   Das BK, Kannan A, Nguyen Q, Gogoi J, et al · · 2021 · cited 9× · PMID 34359608 · DOI 10.3390/cancers13153708
7. An updated review of small-molecule HPK1 kinase inhibitors (2016-present).
   Duan Y, Guo Z, Zhong W, Chen J, et al · · 2024 · cited 6× · PMID 39582317 · DOI 10.1080/17568919.2024.2420630
8. Identification of Novel HPK1 Hit Inhibitors: From In Silico Design to In Vitro Validation.
   Isawi IH, Obeidat RM, Alnabulsi S, Al Zoubi R. · · 2025 · cited 1× · PMID 40362603 · DOI 10.3390/ijms26094366