SAN FRANCISCO, April 02, 2024 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ: FGEN) today announced topline data from the Fortis Therapeutics-sponsored Phase 1 study of FG-3246 (also known as FOR46), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with an MMAE-containing payload, in a dose-escalation and dose-expansion trial enrolling patients with metastatic castration-resistant prostate cancer (mCRPC) whose tumors have progressed on at least one androgen receptor-signaling inhibitor (ARSI).
"We are delighted to showcase the latest encouraging clinical data from the FOR46-001 Phase 1 ADC trial," said Deyaa Adib, M.D., Chief Medical Officer of FibroGen. "We observed a median radiographic progression free survival of 8.7 months in heavily pre-treated patients, who received biologically active doses of FG-3246 in the second line or later setting prior to chemotherapy. These Phase 1 data provide evidence of a favorable safety profile and promising clinical activity as further evidenced by prostate-specific antigen reduction of ≥ 50% and shrinking of measurable disease. We look forward to publishing the totality of the Phase 1 data as we advance the program further in the clinic."
In the Phase 1 dose-escalation portion of the study, ascending dose levels of FG-3246 were administered every 3 weeks. In the dose-expansion arm of the trial, patients were treated at the 2.7 mg/kg adjusted body weight dosing (AjBW) until disease progression. The endpoints were safety, tolerability, and anti-tumor activity as measured by the decline of prostate-specific antigen (PSA) from baseline, objective tumor response rate in patients with measurable disease, and radiographic progression free survival (rPFS).
The completed Phase 1 trial includes a total of 56 patients from the dose-escalation and dose-expansion cohorts. The efficacy analysis includes patients who received a starting dose of FG-3246 of ≥ 1.2 mg/kg in the dose-escalation cohort, and patients who received 2.7 mg/kg AjBW with a histologic diagnosis of adenocarcinoma in the dose-expansion cohort. Patients were heavily pre-treated, having received a median of 5 lines of therapy prior to receiving FG-3246.
In the efficacy analysis, PSA reductions of ≥ 50% were observed in 36% of PSA evaluable patients. For RECIST evaluable patients, 20% met the criteria of a partial response, or tumor reduction in size of ≥ 30%, with a median duration of response of 7.5 months. The median rPFS in this heavily pre-treated patient population was 8.7 months.
The most frequent adverse events were consistent with other MMAE-based ADCs and included infusion related reactions, fatigue, weight loss, neutropenia, and peripheral neuropathy.
"The results from the FOR46-001 Phase 1 study are promising, demonstrating a manageable safety profile and continued robust signals of clinical activity," stated Dr. Rahul Aggarwal, Professor of Medicine at University of California San Francisco and Lead Investigator of the study. "The observed median radiographic progression free survival of 8.7 months in patients treated with a starting FG-3246 dose of 1.2 mg/kg and higher is quite favorable and highlights the therapeutic potential of FG-3246 as a new ADC aimed at a novel target. These findings warrant further investigation and hold promise for addressing the therapeutic needs of patients with CD46 positive prostate cancer. We are also excited about potential combinations with FG-3246 and will be presenting investigator sponsored trial data of FG-3246 in combination with enzalutamide at the upcoming ASCO 2024 annual meeting."
Earlier data from the FOR46-001 trial had been presented at the American Society for Clinical Oncology (ASCO) 2022 annual meeting1, and complete results from the study are being submitted to a medical journal for publication in 2024.
舊金山，2024年4月2日（GLOBE NEWSWIRE）——FibroGen, Inc.（納斯達克股票代碼：FGEN）今天公佈了富通療法贊助的針對FG-3246（也稱爲 FOR46）的1期研究的主要數據，該研究是一種潛在的首創抗CD46抗體偶聯物，載荷含MMAE，該試驗招收了轉移去勢耐藥患者前列腺癌（mcRPC），其腫瘤在至少一種雄激素受體信號抑制劑（ARSI）上進展了。
FibroGen首席醫學官德亞·阿迪布醫學博士說：“我們很高興展示來自 FOR46-001 1期ADC試驗的最新令人鼓舞的臨床數據。”“我們觀察到，在經過大量預治療的患者中，放射照相無進展存活率中位數爲8.7個月，這些患者在化療前的第二線或之後接受了生物活性劑量的 FG-3246。這些1期數據爲良好的安全性以及有希望的臨床活性提供了證據，前列腺特異性抗原減少≥50％和可測疾病的減少進一步證明了這一點。隨着我們在臨床中進一步推進該項目，我們期待公佈第一階段的全部數據。”
在該研究的第 1 階段劑量遞增部分中，每 3 周給藥一次 FG-3246 的劑量水平上升一次。在試驗的劑量擴張組中，患者在疾病進展之前按2.7 mg/kg調整後的體重劑量（aJbW）接受治療。終點是安全性、耐受性和抗腫瘤活性，衡量標準是前列腺特異性抗原（PSA）較基線的下降、可測疾病患者的客觀腫瘤反應率以及射線照相無進展存活率（RPF）。
已完成的1期試驗共包括來自劑量遞增和劑量擴張隊列的56名患者。療效分析包括劑量遞增隊列中接受 ≥ 1.2 mg/kg 的 FG-3246 起始劑量的患者，以及劑量擴張隊列中接受 2.7 mg/kg aJbW 組織學診斷爲腺癌的患者。患者接受了大量的預治療，在接受 FG-3246 之前，平均接受了 5 條線路的治療。
在療效分析中，在36％的PSA可評估患者中，觀察到PSA降低了≥50％。對於RECIST可評估的患者，有20％符合部分緩解或腫瘤大小縮小≥30％的標準，中位緩解持續時間爲7.5個月。在這個經過大量預治療的患者群體中，RPF的中位數爲8.7個月。
最常見的不良事件與其他基於 MMAE 的 ADC 一致，包括輸液相關反應、疲勞、體重減輕、中性粒細胞減少和周圍神經病變。
加州大學舊金山分校醫學教授、該研究首席研究員拉胡爾·阿格瓦爾博士說：“FOR46-001 1期研究的結果令人鼓舞，顯示出可控的安全性和持續的強勁臨床活動信號。”“在 FG-3246 起始劑量爲 1.2 mg/kg 及更高劑量治療的患者中，觀察到的放射照相無進展存活率中位數爲 8.7 個月，這相當不錯，凸顯了 FG-3246 作爲一種針對新靶標的新 ADC 的治療潛力。這些發現值得進一步研究，並有望滿足CD46陽性前列腺癌患者的治療需求。我們還對與 FG-3246 的潛在組合感到興奮，並將在即將召開的 ASCO 2024 年年會上公佈研究人員贊助的 FG-3246 與恩雜魯胺聯合使用的試驗數據。”
FOR46-001 試驗的早期數據已在美國臨床腫瘤學會（ASCO）2022年年會上公佈1，該研究的完整結果將提交給醫學期刊以供2024年發表。
