Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Neoplasms

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Neoplasms, Squamous Cell

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Pancreatic Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Pancreatic Cancer

Camurati-Engelmann Disease

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Route: IV Infusion Frequency: QW Current Dose: 1500mg

Route: IV Infusion Frequency: Q3W Dose: 200mg

BCA101

David Bohr

Debanjali Ghosh

Assuntina Sacco, MD

Gino In, MD

Deborah Wong, MD

Hamza Elmohd

Jameel Muzaffar, MD

DFCI Clinical Trials Hotline

Glen Hanna, MD

Paul Paik, MD

CPDM Nurse Navigator

Sarah Brodeur

Dan Zanberg, MD

Lilli Neal

Carly Fecio

John Kaczmar, MD

Mike Gibson, MD

Beryl Tross

Van Morris, MD

Phillippe Bedard, MD

The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound that targets both EGFR with TGFβ. Based on preclinical data, this bifunctional antibody may exert synergistic activity in patients with EGFR-driven tumors.

This is a Phase 1/1b, open-label study, which consists of dose escalation parts (Part A) followed by expansion cohorts (Part B) for both single agent BCA101 and combination BCA101 plus pembrolizumab.

The study population in dose escalation (Part A) of single agent BCA101 consists of subjects with EGFR-driven advanced solid tumors refractory to standard of care or for whom no standard of care is available. Dose escalation (Part A) of combination BCA101 and pembrolizumab consists of subjects with either Squamous Cell Carcinoma of the Head and Neck (HNSCC) or Squamous Cell Carcinoma of the Anal Canal (SCCAC) whose tumors are refractory to standard of care or for whom no standard of care is available.

Once the maximum tolerated dose (MTD) / recommended dose (RD) of single agent BCA101 is determined, the study will continue with expansion cohorts (Part B) with select tumor types. Expansion cohorts for single agent BCA101 will include cutaneous squamous cell carcinoma. Planned expansion cohorts for the combination of BCA101 and pembrolizumab include: 1) HNSCC and 2) SCCAC.

Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors

First-in-Human, Phase 1/1b, Open-label, Multicenter Study of Bifunctional EGFR/TGFβ Fusion Protein BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-Driven Advanced Solid Tumors

Incidence of DLTs during the first cycle of treatment with BCA101 monotherapy or the combination of BCA101 and pembrolizumab.

Determine objective response rate in each part of the study, per RECIST v1.1 and iRECIST

Determine clinical benefit rate in each part of the study, per RECIST v1.1 and iRECIST

Determine PFS in each part of the study, per RECIST v1.1 and iRECIST

Determine duration of response in each part of the study, per RECIST v1.1 and iRECIST

Determine survival rates in each part of the study.

Incidence and titer of anti-drug-antibodies

Merck Sharp & Dohme LLC

Bicara Therapeutics

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.

Hunan Zhaotai Yongren Medical Innovation Co. Ltd.

Guangdong Zhaotai InVivo Biomedicine Co. Ltd.

Second Affiliated Hospital of Guangzhou Medical University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors	NCT04429542	Head and Neck S... Squamous Cell C... Colorectal Canc... Squamous Cell C... EGFR Amplificat... Epithelial Ovar... Pancreas Cancer Cutaneous Squam... Head and Neck N... Carcinoma, Squa... Squamous Cell C...	BCA101 Pembrolizumab	18 Years -	Bicara Therapeutics
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

Spots Global Cancer Trial Database for tgfβ

Every month we try and update this database with for tgfβ 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 tgfβ

Every month we try and update this database with for tgfβ 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 tgfβ 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.