foritinib (SAF-189) / Fosun Pharma - LARVOL DELTA

Fosun Pharma (02196.HK): Fosun Wanbang withdraws the registration application for foritinib succinate capsules and will resubmit it after completing the documentation. (FUTU) - "Fosun Pharma (02196.HK) announced that its controlling subsidiary, Fosun Wanbang (Jiangsu) Pharmaceutical Group Co., Ltd. (hereinafter referred to as 'Fosun Wanbang'), has recently received a notice from the National Medical Products Administration (NMPA) approving the withdrawal of the registration application for disodium foritinib capsules (Project Code: SAF-189; hereinafter referred to as 'the new drug')."

Regulatory • Non Small Cell Lung Cancer

A Multicenter, Open-label, Randomized Phase III Clinical Trial: Evaluating the Efficacy and Safety of SAF-189s Assisted Therapy Compared to Platinum-based Chemotherapy in Fully Resected Patients with Stage II to IIIB ALK-positive or ROS1-positive NSCLC (ChiCTR) - P3 | N=210 | Not yet recruiting | Sponsor: Shanghai Oriental Hospital; Fosun Wanbang (Jiangsu) Pharmaceutical Group Co., Ltd.

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

Shanghai Fosun Pharmaceutical’s subsidiary, Fosun Wanbang, has received approval from the National Medical Products Administration for a clinical trial of Foritinib Succinate Capsules (TipRanks) - "This new drug is intended for the adjuvant treatment of non-small cell lung cancer with specific genetic markers and marks a significant step in the company’s ongoing efforts to expand its oncology portfolio."

New trial • Non Small Cell Lung Cancer

Pharmacokinetics, mass balance, and metabolism of [14C]SAF-189s, a potent anaplastic lymphoma kinase/c-ROS proto-oncogene 1 inhibitor in humans: Metabolism potentially affected by interaction of cytochrome P450 enzymes and intestinal microbiota. (PubMed, Drug Metab Dispos) - "The results demonstrated that SAF-189s and its metabolites were primarily excreted via feces, with metabolism likely mediated by both the cytochrome P450 system and gut microbiota. These findings provide essential pharmacokinetic and safety data, encourage further studies on drug interactions and dose adjustments, and support the involvement of gut microbiota, thereby guiding future research."

Journal • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • CYP3A4 • ROS1

Fosun Pharma’s Independently Developed Innovative Lung Cancer Drug Foritinib (SAF-189) Marketing Authorization Application Has Been Accepted by NMPA (Fosun Pharma Press Release) - "Fosun Pharma announced that the marketing authorization application for its independently developed new drug, foritinib Succinate Capsules...has been accepted by the National Medical Products Administration (NMPA). The New Drug is primarily indicated for the treatment of non-small cell lung cancer (ALK+) and non-small cell lung cancer (ROS1+), etc. The indication under this application is for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC)...The REMARK study is an open-label, randomized, Phase III clinical trial that enrolled previously untreated patients with ALK-positive advanced NSCLC...As of March 2024, with a median follow-up of 16.7 months, the study found that the foritinib treatment group had a significantly improved PFS compared to the crizotinib treatment group."

China filing • Non Small Cell Lung Cancer

A Study of IBI363 in Combination With Bevacizumab or Furuitinib in Subjects With Advanced Colorectal Cancer (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: Wuhan Union Hospital, China | Active, not recruiting ➔ Recruiting | N=49 ➔ 260 | Trial completion date: Jul 2025 ➔ Jul 2026

Enrollment change • Enrollment open • Trial completion date • Colorectal Cancer • Oncology • Solid Tumor

Randomized, Open-Label, Phase III Study of SAF-189s Versus Crizotinib in First-Line ALK-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) (IASLC-WCLC 2024) - "Safety profile of SAF-189s was consistent with previous reports and without new safety signals. SAF-189s (n=139) Crizotinib (n=136) PFS by IRC mPFS, months (95% CI) NR 13.93 HR (95% CI) 0.23 (0.14, 0.38) PFS by INV mPFS, months (95% CI) NR 13.80 HR (95% CI) 0.29 (0.19, 0.45) ORR by IRC, % 92.8 80.9 mDOR by IRC, months (95% CI) NR 15.93 CNS-TTP by IRC, months NR 19.32 HR (95% CI) 0.04 (0.01, 0.14) PFS of pts with baseline CNS metastases, months - 9.56 HR (95% CI) 0.14 (0.05, 0.37) C-ORR by IRC, n (%) 10 (100) 9 (50.0) TRAE, n (%) Any grade 135 (97.8) 133(98.5) Grade ≥3 52 (37.7) 75 (55.6) Leading to dose interruption 37 (26.8) 48 (35.6) Leading to dose reduction 33 (23.9) 51 (37.8) Leading to discontinuation 5 (3.6) 3 (2.2) SAF-189s (n=139) Crizotinib (n=136) PFS by IRC mPFS, months (95% CI) NR 13.93 HR (95% CI) 0.23 (0.14, 0.38) PFS by INV mPFS, months (95% CI) NR 13.80 HR (95% CI) 0.29 (0.19, 0.45) ORR by IRC, % 92.8 80.9 mDOR by IRC, months (95% CI) NR 15.93 CNS-TTP by..."

Clinical • Metastases • P3 data • Diabetes • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ALK

Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLC (clinicaltrials.gov) - P3 | N=275 | Active, not recruiting | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Metastases • New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Population pharmacokinetics and exposure-response analyses of SAF-189s in Chinese patients with ALK+/ROS1+ non-small cell lung cancer. (PubMed, Front Pharmacol) - "The 210-mg dose group had a significantly higher safety risk, while the 160-mg dose group was well-tolerated. Thus, 160 mg of SAF-189s once daily was selected as the recommended phase III dose for the ALK+/ROS1+ or ROS1+ NSCLC patients."

Journal • PK/PD data • Diabetes • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • ROS1

Phase II study of foritinib in #ROS1 NSCLC @LancetRespirMed. In the phase IIB at 160mg, the RR in TKI naive ROS1 NSCLC was 88% overall and 90% in those with baseline brain metastases. Most common G3+ related AEs were hyperglycemia (12%) and QTc (6%).

Foritinib in advanced ROS1-rearranged non-small-cell lung cancer in China: a multicentre, open-label, single-arm, phase 2 study. (PubMed, Lancet Respir Med) - P1/2 | "Foritinib showed systemic and intracranial antitumour activity and good tolerability in ROS1-inhibitor-naive patients with ROS1-rearranged NSCLC. Foritinib represents a promising treatment for these patients, especially in those with CNS metastases."

Journal • Metastases • P2 data • Diabetes • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

Foritinib, a type II ROS1 inhibitor for NSCLC. (PubMed, Lancet Respir Med) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Effect of High-Fat Food on the Pharmacokinetic Profile and Safety of SAF-189s, an ALK/ROS1 Inhibitor, in Healthy Chinese Adults. (PubMed, Drugs R D) - "A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs."

Journal • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Pain

ctDNA analysis of SAF-189s efficacy in ALK+ advanced non-small cell lung cancer (NSCLC) (ESMO 2023) - P1/2 | "Gene co-occurrence survival analysis showed that mPFS of pts harboring FAT3/FAT4 mutations were significantly shorter than those without FAT3/FAT4 mutations (8.9 mo vs 16.5 mo, p=0.012). Conclusions Clinical utility of ctDNA was demonstrated, not only at baseline by identifying fusion types and subgroups of ALK+ NSCLC pts that may benefit more from SAF-189s, but also at progression by tracking ALK-resistant mutations."

Circulating tumor DNA • Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4 • FAT3 • FAT4 • ROS1 • TP53

Updated Results of SAF-189s in ROS1 inhibitor-naïve patients with ROS1-positive advanced Non-Small Cell Lung Cancer (NSCLC) (ESMO Asia 2023) - No abstract available

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase II study of SAF-189s in patients with advanced ROS1 fusion-positive non-small cell lung cancer (ESMO Asia 2022) - P1/2 | "Conclusions These findings demonstrate the promising clinical activity and a tolerable toxicity profile of SAF-189s in pts with advanced ROS1+ NSCLC, with or without crizotinib treatment. Clinical trial identification NCT04237805."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

SAF-189s in advanced, ALK-positive, non–small cell lung cancer: Results from a first-in-human phase 1/2, multicenter study. (ASCO 2022) - P1/2 | "SAF-189s showed clinical antitumor activity and was well tolerated in patients with advanced, ALK+ NSCLC, including those with brain metastases and pretreated with crizotinib. SAF-189s represents a promising, next-generation, targeted therapy for patients with ALK+ NSCLC."

Clinical • P1/2 data • Diabetes • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

A Phase I/II Clinical Study of SAF-189s in Non-small Cell Lung Cancer (NSCLC) Patients (clinicaltrials.gov) - P1/2; N=280; Recruiting; Sponsor: Shanghai Fosun Pharmaceutical Development Co, Ltd.; Trial completion date: Jun 2023 ➔ Mar 2026; Trial primary completion date: Jun 2022 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

A Phase I/II Clinical Study of Foritinib Succinate in Non-small Cell Lung Cancer (NSCLC) Patients (clinicaltrials.gov) - P1/2; N=280; Recruiting; Sponsor: Shanghai Fosun Pharmaceutical Development Co, Ltd.

Clinical • New P1/2 trial