The study is composed of fasted dose cohorts and fed dose cohort. BB3008 will be administered orally daily alone as monotherapy in all cohorts. In the fasted dose cohorts, the subjects will receive once daily of BB3008 monotherapy fasted across approximately 6 ascending dose levels. The starting dose is 80 mg/day. In the fed dose cohort, the subjects will receive once daily of BB3008 monotherapy in a fed condition. The dose selected for fed dose cohort must be deemed safe as assessed by safety monitoring committee (SMC).

BB3008 tablets will be administered orally once daily (QD).

BB3008 tablet

Qi Wang, PhD

Mengzhao Wang, MD

Jing Huang, MD

This is a Phase 1 dose escalation study to evaluate the safety, tolerability, pharmacokinetics, efficacy and preliminary food effect of BB3008 as monotherapy in subjects with advanced solid tumors.

This first-in-human (FIH) study of BB3008 will evaluate safety, tolerability, pharmacokinetics (PK) efficacy and preliminary food effect of BB3008 in subjects with advanced solid tumors. The primary objective is to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of BB3008 as monotherapy, and to evaluate the safety and tolerability of BB3008. The secondary objectives include the assessments of PK profile, preliminary efficacy, preliminary food effect (FE) and preliminary metabolites identification of BB3008. The exploratory objectives are to explore biomarkers and C-QTcF analysis.

A Phase 1 Study of BB3008 in Participants With Advanced Solid Tumors

A Phase I, Open-label, Multicenter Study to Assess Safety, Tolerability, Pharmacokinetic, Efficacy and Preliminary Food Effect of BB3008 Tablet Administered Orally to Patients With Advanced Solid Tumors

To assess the safety and tolerability of BB3008 tablet as monotherapy in subjects with advanced solid tumors and to determine the maximum tolerated dose (MTD) of BB3008 tablet, and to provide a basis for determination of the recommended dose (RP2D) for Phase II clinical trials.

AEs and SAEs will be characterized by type, seriousness, relationship to study treatment, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 5.0) and timing.

Blood samples will be collected for PK analyses

Tumor response measured by radiologic imaging techniques at baseline and throughout the study.

BrodenBio Co., Ltd.

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Pembrolizumab

Coal Tar

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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

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

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

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

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

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.

CFI-402411

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

Treadwell Therapeutics Clinical Trials

Ceonne Kim

Michele Azada

Ingrid Palmer

Donna Jones

Robinson Katie

Miller Elizabeth

Munir Chowdhury

Isabel Jimenez

Melissa Hackmaster

Carly Mack

Scott Laurie

Ashley Adile

Jane Koh

Omid Hamid, Dr

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.

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.

Dose escalation and expansion for monotherapy and combination arms with pembrolizumab

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

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

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.

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

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

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.

Safety tables and pharmacokinetic tables will be assessed.

For all subjects the overall response rates of complete response and partial response will be calculated and summarized by dose cohort and overall.

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.

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.

Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration tabulated by dose group.

Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax tabulated by dose group.

Tmax will be assessed by the time to achieve maximum plasma concentration and will be tabulated by dose group.

Cmin will be calculated through the measured pre-dose plasma concentration and tabulated by dose group.

Elimination half life will be calculated and tabulated by dose group.

The effects of CFI-402411 on pharmacodynamic biomarkers (cytokine levels) will be assessed by percent changes from baseline.

TIO Discovery Engine

Treadwell Therapeutics, Inc

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Camurati-Engelmann Disease

Immunomodulating Agents

Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.

CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.

CAR-T cells targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR

Zhenfeng Zhang, MD,PhD

Peng Li, PhD

Xianhong Xiang, MD,PHD

Yonghui Huang, MD,PHD

Deji Chen, MD,PhD

The third generation of CAR-T cells that target GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function of the these individual or combination of the CAR-T cells for immunotherapy of human cancer patients with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR

-CAR-T cell immunotherapy on human cancers will firstly be tested.

1. Choose appropriate patients with advanced lung or other cancers,with written consent for this study;
2. Perform biopsy to determine the expression of HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 of the tumor by western blotting or IHC;
3. Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed;
4. To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR

   -DAP10-CAR with knockdown of PD1/HPK1;
5. Other cancers with these cell surface antigen expressions are also recruited if needed;
6. Evaluate the clinical results as needed.

Use engineered CAR-T cells to kill cancer cells with certain targets.

GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers

CAR-T Targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR for Immunotherapy of Lung Cancer: Phase I Clinical Trial

A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR T cells,which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.

Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.

Median CAR-T cell persistence will be measured by quantitative rt-PCR.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1 Study of BB3008 in Participants With Advanced Solid Tumors	NCT06143007	Advanced Solid ...	BB3008 tablet	18 Years - 78 Years	BrodenBio Co., Ltd.
Safety and Efficacy Study of CFI-402411 in Subjects With Advanced Solid Malignancies	NCT04521413	Advanced Solid ...	CFI-402411 Pembrolizumab	18 Years -	Treadwell Therapeutics, Inc
GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers	NCT03198052	Lung Cancer Cancer Immunotherapy CAR-T Cell	CAR-T cells tar...	18 Years - 75 Years	Second Affiliated Hospital of Guangzhou Medical University
Safety and Efficacy Study of CFI-402411 in Subjects With Advanced Solid Malignancies	NCT04521413	Advanced Solid ...	CFI-402411 Pembrolizumab	18 Years -	Treadwell Therapeutics, Inc

Spots Global Cancer Trial Database for hpk1

Every month we try and update this database with for hpk1 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hpk1

Every month we try and update this database with for hpk1 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hpk1 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.