FIT-001 / Guangzhou FineImmune Biotech - LARVOL DELTA

A Phase 1 Clinical Trial of the Farnesyltransferase Inhibitor KO-2806 in Combination with Cabozantinib in Renal Cell Carcinoma (KCRS 2025) - P1, P2 | "Recent clinical trials (NCT03719690, NCT02383927) of the FTI tipifarnib in patients with HRAS-mutant (HRAS-m) head and neck squamous cell carcinoma harboring high variant allele frequency mutations (VAF ≥20%) showed objective response rates of up to 50% and favorable long-term outcomes...The study began accrual in October 2023, and recruitment is ongoing. Significance & Vision FIT-001 is assessing the safety, tolerability, pharmacokinetics, PD, and preliminary antitumor activity of KO-2806 in combination with cabozantinib in patients with ccRCC and non-ccRCC."

Clinical • Combination therapy • IO biomarker • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HRAS

Farnesyl transferase inhibitor KO-2806 enhances the antitumor activity of cabozantinib in ccRCC tumors that progress on anti-VEGFR agents (AACR 2025) - P1, P3 | "The combination of KO-2806 and cabozantinib led to deeper and more consistent tumor growth inhibition than cabozantinib alone in tumor models that had progressed on axitinib or lenvatinib, two TKIs used to treat RCC...Taken together, our findings demonstrate that KO-2806 augments the antitumor activity of cabozantinib, even after prior exposure to anti-VEGFR treatment, largely by enhancing anti-angiogenesis via mTORC1 signaling inhibition in endothelial cells. These data strongly support our clinical evaluation of KO-2806 as a combination partner with cabozantinib in ccRCC as part of the ongoing Phase 1 FIT-001 trial (NCT06026410)."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD31 • PECAM1 • RHEB

KO-2806, a next-generation farnesyl transferase inhibitor, re-sensitizes KRAS G12C NSCLC tumors to KRAS G12C mutant-specific inhibitors through mTOR signaling inhibition (EORTC-NCI-AACR 2024) - P1 | "Background: The approval of the KRASG12C mutant-selective inhibitors sotorasib and adagrasib has revolutionized the clinical landscape of non-small cell lung cancer (NSCLC); however, adaptive resistance due to compensatory reactivation of mTOR and MAPK signaling pathways limits their clinical effectiveness...This KO-2806/adagrasib combination is part of FIT-001, a phase 1 first-in-human clinical trial of KO-2806 as a monotherapy and in combination with targeted anti-tumor agents (NCT06026410)... Our findings demonstrate that KO-2806 is effective at overcoming adaptive resistance to KRASG12C inhibitors in KRAS inhibitor-pretreated animals by robust inhibition of adaptive compensatory mTOR activation. Taken together with our previous results, this new data strengthens the therapeutic case for farnesyl transferase inhibition in combination with adagrasib in KRASG12C NSCLC patients irrespective of prior KRAS inhibitor treatment."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EIF4EBP1 • KRAS • RHEB

Individualized Tumor Specific TCR- T Cells in the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Guangzhou FineImmune Biotechnology Co., LTD. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jul 2024 ➔ Oct 2025

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

FIT-001: A phase 1 clinical trial of the farnesyl transferase inhibitor KO-2806 alone or as part of combination therapy for advanced solid tumors. (ASCO 2024) - P1, P2 | "Recent clinical trials (NCT03719690, NCT02383927) of the FTI, tipifarnib, in patients with HRAS-mutant (HRAS-m) head and neck squamous cell carcinoma harboring high variant allele frequency mutations (VAF ≥20%), showed objective response rates of up to 50% and favorable long-term outcomes...In preclinical studies, KO-2806 has been shown to: (1) enhance tumor growth inhibition of tyrosine kinase inhibitors, including cabozantinib, in multiple clear cell renal cell carcinoma (ccRCC) cell line- and patient-derived xenograft models; and (2) enhance activity of KRAS inhibitors, including adagrasib, in KRAS mutant non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC) mouse models...Other combination arms may also be considered. The study began accrual in October 2023."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HRAS • KRAS

FIT-001: A phase 1 clinical trial of the farnesyl transferase inhibitor KO-2806 alone or as part of combination therapy for advanced solid tumors (AACR 2024) - P1, P2 | "Recent clinical trials (NCT03719690, NCT02383927) of the FTI, tipifarnib, in patients with HRAS-mutant (HRAS-m) head and neck squamous cell carcinoma harboring high variant allele frequency mutations (VAF ≥20%), showed objective response rates of up to 50% and favorable long-term outcomes...In preclinical studies, KO-2806 has been shown to: (1) enhance tumor growth inhibition of tyrosine kinase inhibitors, including cabozantinib, in multiple clear cell renal cell carcinoma (ccRCC) cell line- and patient-derived xenograft models; and (2) enhance activity of KRAS inhibitors, including adagrasib, in KRAS mutant non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC) mouse models...Other combination arms may also be considered. The study began accrual in October 2023."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HRAS • KRAS

Individualized Tumor Specific TCR- T Cells in the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Guangzhou FineImmune Biotechnology Co., LTD. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Jul 2023 ➔ Jul 2024

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

Individualized Tumor Specific TCR- T Cells in the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Guangzhou FineImmune Biotechnology Co., LTD. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Jul 2022 ➔ Jul 2023

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

Individualized Tumor Specific TCR- T Cells in the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Guangzhou FineImmune Biotechnology Co., LTD.; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Jul 2021 ➔ Jul 2022

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