GFH018 / GenFleet Therap - LARVOL DELTA

A Trial of GFH018 and Toripalimab in Combination With Concurrent Chemoradiotherapy in Stage III NSCLC Chemoradiotherapy in Stage III NSCLC (clinicaltrials.gov) - P2 | N=65 | Completed | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Trial of GFH018 and Toripalimab in Combination With Concurrent Chemoradiotherapy in Stage III NSCLC Chemoradiotherapy in Stage III NSCLC (clinicaltrials.gov) - P2 | N=65 | Active, not recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: May 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GFH018 and toripalimab combination therapy for previously treated recurrent or metastatic nasopharyngeal carcinoma: Results from a phase 1b/2 study. (PubMed, Clin Cancer Res) - "The combination of GFH018 and toripalimab showed a manageable toxicity profile and durable antitumor activity in R/M NPC patients, especially those without prior ICI exposure."

Journal • P1/2 data • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • CD8 • TGFB1

Discovery of a Selective, Novel TGF-βR1 Inhibitor GFH018 for the Treatment of Solid Tumors. (PubMed, J Med Chem) - "In murine tumor mouse models, either the monotherapy of GFH018 or the combination with an anti-PD-L1 antibody suppressed tumor growth, and potent inhibition of cancer cell migration in vivo was observed. Mechanistic studies revealed that GFH018 not only reactivated the immune system by blocking Treg- and M2 macrophage-mediated immunosuppression but also inhibited tumor vascular angiogenesis."

Journal • Oncology • Solid Tumor • TGFB1

A Trial of GFH018 and Toripalimab in Combination with Concurrent Chemoradiotherapy in Stage III NSCLC Chemoradiotherapy in Stage III NSCLC (clinicaltrials.gov) - P2 | N=65 | Active, not recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | Trial completion date: Jan 2025 ➔ Jul 2025 | Trial primary completion date: Oct 2024 ➔ May 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-β receptor I inhibitor, in patients with advanced solid tumors. (PubMed, BMC Cancer) - P1 | "GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies."

Clinical • Journal • Metastases • P1 data • Cardiovascular • Hematological Disorders • Immunology • Oncology • Renal Disease • Solid Tumor • Thymic Carcinoma • Thymus Cancer • TGFB1

First-in-human study of GFH018, a small molecule inhibitor of transforming growth factor-β receptor I inhibitor, in patients with advanced solid tumors (BMC Cancer) - P1 | N=50 | NCT05051241 | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | "Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached....The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed....Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-β1 levels were not associated with clinical responses."

P1 data • Solid Tumor • Thymic Carcinoma

A Study of GFH018 in Combination With Toripalimab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=148 | Completed | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Dec 2023

Combination therapy • Metastases • Trial completion • Trial completion date • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Trial of GFH018 and Toripalimab in Combination With Concurrent Chemoradiotherapy in Stage III NSCLC Chemoradiotherapy in Stage III NSCLC (clinicaltrials.gov) - P2 | N=65 | Active, not recruiting | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of GFH018 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=50 | Completed | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Feb 2023 ➔ Aug 2022 | Trial primary completion date: Dec 2022 ➔ Aug 2022

Metastases • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

GFH018, a small molecular inhibitor targeting TGF-βRI kinase, in patients with advanced solid tumors: final results of the phase I study. (ASCO 2023) - P1 | "GFH018 shows a favorable safety profile and preliminary anti-tumor activity. The clinical studies of GFH018 in combination with Toripalimab and with Toripalimab + concurrent chemoradiotherapy are ongoing. Clinical trial information: NCT05051241."

Clinical • IO biomarker • Metastases • P1 data • Anemia • Cardiovascular • Hematological Disorders • Oncology • Renal Disease • Solid Tumor • Thymic Carcinoma • Thymus Cancer • TGFB1

A phase Ib/II study of GFH018 in combination with toripalimab in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC). (ASCO 2023) - P1/2 | "GFH018 combined Toripalimab was well tolerated and demonstrated preliminary efficacy in pts with R/M NPC. Specifically, in pts who had not previously received ICIs, promising antitumor activity was observed supporting further investigation to this group of pts. Clinical trial information: NCT04914286."

Combination therapy • Metastases • P1/2 data • Anemia • Back Pain • Endocrine Disorders • Epstein-Barr Virus Infections • Fatigue • Hematological Disorders • Immune Modulation • Infectious Disease • Musculoskeletal Pain • Nasopharyngeal Carcinoma • Oncology • Pain • Solid Tumor • PD-1 • TGFB1

2023 ASCO | Multi-center Data for Combination Study of GenFleet’s GFH018 (TGF-β R1 inhibitor) with Anti-PD-1 Antibody Demonstrates Significant Potential to Enhance Efficacy of Immune Checkpoint Inhibitors among ICI-naïve Patients (PRNewswire) - P1b/2 | N=195 | NCT04914286 | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | "GenFleet Therapeutics...published the latest results from the phase Ib/II study of GFH018 (TGF-β R1 inhibitor) with toripalimab (anti-PD-1 antibody at the 2023 American Society of Clinical Oncology Meeting in Chicago. The data demonstrated promising anti-tumor activity and tolerability among patients with recurrent/metastatic nasopharyngeal carcinoma (R/M NPC)....As of 20 April 2023, among the 32 patients with post-baseline tumor assessments, the overall response rate (ORR) was 31.3%, and disease control rate (DCR) was 50%; 10 pts achieved partial response (PR), and 6 pts with stable disease (SD). Among 17 ICI-naïve patients (without prior treatment of ICIs), the ORR was 47.1%, and DCR was 64.7%, 8 pts achieved PR, and 3 pts SD; a total of 4 pts that achieved PR have their target lesion decreased by over 50% from baseline."

P1/2 data • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

A Trial of GFH018 in Combination With Toripalimab and Concurrent Chemoradiotherapy in Stage III NSCLC (clinicaltrials.gov) - P2 | N=65 | Recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of GFH018 in Combination With Toripalimab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=195 | Recruiting | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | Trial completion date: Nov 2023 ➔ Jun 2024 | Trial primary completion date: Jul 2023 ➔ Dec 2023

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Study of GFH018 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2023 ➔ Feb 2023

Enrollment closed • Metastases • Trial completion date • Oncology • Solid Tumor

Phase I study of GFH018, a small molecular TGF-βRI inhibitor, in patients (pts) with advanced solid tumors (ESMO 2022) - P1 | "Conclusions GFH018 shows a favorable safety profile and is now being tested in combination with an anti-PD-1 antibody in patients with advanced malignancies. Further studies are warranted."

Clinical • P1 data • Oncology • Solid Tumor • Thymic Carcinoma • Thymus Cancer • TGFB1

GenFleet Therapeutics to Present Data from Phase I Trial of GFH018 Monotherapy at the 2022 European Society for Medical Oncology Annual Meeting (GlobeNewswire) - P1 | N=60 | NCT05051241 | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | "GenFleet Therapeutics...announced the results from phase I study of GFH018 (TGF-β R1 inhibitor) monotherapy (NCT05051241) for treatment of advanced solid tumor will be presented as a poster at the 2022 European Society for Medical Oncology Meeting in Paris on September 12th....The median lines of prior therapy were≥3. No dose-limiting toxicities were observed, the maximum tolerated dose was not reached, and no patients discontinued the study treatment due to adverse events....PK of GFH018 was linear and dose-independent with mean half-life in the range of 3.11 hours to 8.30 hours. Of 24 evaluable patients, 5 achieved stable disease. A patient with thymic carcinoma receiving 50 mg achieved a durable stable disease with tumor shrinkage (maximum lesion decreased by 18.4% and has stayed on treatment for 185 days as of the data cut-off date."

P1 data • Oncology • Solid Tumor

A Study of GFH018 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2022 ➔ Jun 2023 | Initiation date: Sep 2021 ➔ Aug 2019 | Trial primary completion date: May 2022 ➔ Dec 2022

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Oncology • Solid Tumor

GenFleet Receives CTAs Approval for Two Phase II Combination Studies of TGF-β R1 Inhibitor (GFH018) with PD-1 Inhibitor (PRNewswire) - "GenFleet Therapeutics...announced China's National Medical Products Administration (NMPA) has approved the Clinical Trial Applications (CTAs) for GFH018 in two clinical studies for combination therapies. One study is a phase Ib/II trial of GFH018 with PD-1 inhibitor treating patients with advanced solid tumors; the other study is a phase II trial of GFH018, PD-1 inhibitor with concurrent chemoradiotherapy treating patients with locally advanced & unresectable NSCLC...and the data will soon be published in relevant international medical conference."

New P1/2 trial • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Trial of GFH018 in Combination With Toripalimab and Concurrent Chemoradiotherapy in Stage III NSCLC (clinicaltrials.gov) - P2 | N=65 | Not yet recruiting | Sponsor: Genfleet Therapeutics (Shanghai) Inc.

Combination therapy • New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of GFH018 in Combination With Toripalimab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=195 | Recruiting | Sponsor: Zhejiang Genfleet Therapeutics Co., Ltd. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Cholangiocarcinoma • Colorectal Cancer • Esophageal Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

GenFleet Announces First Patient Dosed in Phase Ib/II Trial of TGF-β R1 Inhibitor in Combination with PD-1 Inhibitor in Global Multi-center Research (PRNewswire) - "GenFleet Therapeutics...announced the first patient with metastatic sigmoid adenocarcinoma has been dosed in Perth, Australia in a phase Ib/II trial of GFH018 in combination with toripalimab (anti-PD-1 monoclonal antibody) as part of global multi-center clinical research. GenFleet also received IND approval from the food and drug administrative authorities in China's Taiwan to proceed with phase Ib/II trial of GFH018 in combination with toripalimab in patients with multiple solid tumors....The primary objective of this combination study is to evaluate the safety/tolerability of GFH018 with toripalimab."

New P1/2 trial • Trial status • Oncology • Solid Tumor