FibroGen Announces Presentation of Positive Interim Data from the Phase 1b Study of FG-3246 (FOR46) in Combination with Enzalutamide in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC) at the 2024 American Society of Clinical Oncology Annual Meeting
FibroGen announced positive interim data from a Phase 1b study of FG-3246 (FOR46) in combination with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. Presented at the 2024 ASCO Annual Meeting, the study revealed a median radiographic progression-free survival (rPFS) of 10.2 months in biomarker-unselected patients. FG-3246, an anti-CD46 antibody-drug conjugate, showed an acceptable safety profile with adverse events similar to other MMAE-based therapies. The recommended Phase 2 dose for FG-3246 is set at 2.1 mg/kg every three weeks alongside enzalutamide at 160 mg daily.
The trial involved 17 patients, most of whom had received at least two prior androgen receptor signaling inhibitors. The study explored dose escalation with and without granulocyte colony-stimulating factor (G-CSF) support. The primary endpoint was to determine the maximally tolerated dose (MTD) of FG-3246, established at 2.1 mg/kg ABW with primary G-CSF prophylaxis in combination with enzalutamide.
- Median radiographic progression-free survival (rPFS) of 10.2 months.
- Acceptable safety profile, similar to other MMAE-based therapies.
- Recommended Phase 2 dose established: 2.1 mg/kg every three weeks.
- High prior androgen receptor signaling inhibitor usage among participants.
- Primary endpoint achieved: maximally tolerated dose (MTD) of FG-3246 determined.
- Study included only 17 patients, limiting statistical power.
- Frequent adverse events: fatigue, weight loss, elevated transaminases, neutropenia, and peripheral neuropathy.
- Patients treated with prior chemotherapy in the castration-resistant setting were excluded.
- No detailed efficacy data on overall survival or quality of life improvements.
The interim data from the Phase 1b study of FG-3246 (FOR46) in combination with enzalutamide is promising for patients with metastatic castration-resistant prostate cancer (mCRPC). The median radiographic progression-free survival (rPFS) of 10.2 months is a significant outcome in this patient population, especially considering that over 70% had prior treatments with at least two androgen receptor signaling inhibitors (ARSIs). This could indicate a potential benefit over existing therapies, particularly for those patients who have exhausted other options.
The acceptable safety profile is equally important. Adverse events like fatigue, weight loss and neutropenia are expected with antibody-drug conjugates (ADCs) carrying an MMAE payload. However, the safety management with granulocyte colony-stimulating factor (G-CSF) support is noteworthy and suggests that side effects can be managed effectively, enabling patients to continue therapy without severe interruptions.
Another promising aspect is the potential use of the CD46-directed PET imaging probe (89Zr-DFO-YS5) as a predictive biomarker, which could personalize treatment in the future by identifying patients most likely to benefit from FG-3246.
The results of this Phase 1b study signify an advancement in the treatment of mCRPC. The median rPFS of 10.2 months surpasses some current treatment benchmarks, showing that combining FG-3246 with enzalutamide may offer an effective new line of therapy. This is particularly relevant given the patient population's heavy pretreatment profile with androgen receptor signaling inhibitors.
The determination of the maximally tolerated dose (MTD) at 2.1 mg/kg with G-CSF support establishes a clear pathway for further studies. This dosing regimen will be important as it progresses into Phase 2, aligning with the standard dosing of enzalutamide at 160 mg/day, which is already well understood in clinical practice.
Furthermore, the ongoing collaboration with the University of California San Francisco (UCSF) and plans to meet with the FDA are positive indicators of the rigorous development and potential future approval process. This demonstrates a structured and methodical approach to bringing a new therapy to market.
- FG-3246 and enzalutamide combination therapy led to a median radiographic progression free survival (rPFS) of 10.2 months in biomarker unselected patients
- FG-3246 demonstrated an acceptable safety profile; adverse events consistent with those observed in other antibody drug conjugate therapies with a MMAE payload
- Recommended Phase 2 dose of FG-3246 was established at 2.1 mg/kg every 3 weeks in combination with enzalutamide given at the standard dose of 160 mg daily
SAN FRANCISCO, May 23, 2024 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ: FGEN) today announced positive interim results from the dose escalation portion of the investigator-sponsored Phase 1b/2 study conducted by the University of California San Francisco of FG-3246 (FOR46), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with a MMAE-containing payload, in combination with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
“We are excited to announce that FG-3246 in combination with enzalutamide in patients with mCRPC demonstrated clinically meaningful early signals of efficacy,” commented Deyaa Adib, M.D., Chief Medical Officer of FibroGen. “These data further validate and build upon the encouraging activity we observed in the recently reported Phase 1 monotherapy data of FG-3246, as well as in preclinical models where the combination of FG-3246 with enzalutamide enhanced its tumor cytotoxic activity. We look forward to continuing our collaboration with the University of California San Francisco and plan to provide additional clinical data from this trial when available.”
The presentation includes data from 17 biomarker unselected patients in the dose escalation portion of the trial. Eligibility criteria for the trial included patients who received at least one prior androgen receptor signaling inhibitor (ARSI) while patients who were treated with prior chemotherapy in the castration resistant setting were excluded. Over
The most frequent adverse events were consistent with other MMAE-based ADCs and included fatigue, weight loss, elevated transaminases, neutropenia, and peripheral neuropathy.
Additionally, a baseline CD46-directed PET imaging probe utilizing the same antibody backbone as FG-3246 (89Zr-DFO-YS5) was obtained in a subset of patients and demonstrated tumor uptake in multiple lesions.
“I am very encouraged by the preliminary evidence of efficacy we have seen with FG-3246 and enzalutamide, specifically the potential for clinically meaningful prolongation of rPFS, as well as the safety profile,” added Dr. Rahul Aggarwal, Professor of Medicine at the University of California San Francisco, and Principal Investigator of the study. “We will continue to evaluate this combination in the Phase 2 portion of the trial and further explore the potential of 89Zr-DFO-YS5 as a predictive biomarker of response.”
The poster presentation, titled “A Phase 1b dose escalation study of FOR46, a novel antibody-drug conjugate targeting a tumor-specific epitope of CD46, in combination with enzalutamide (Enza) in patients with metastatic castration resistant prostate cancer (mCRPC)” is scheduled for the poster session taking place on June 2, 2024 from 9:00 am to 12:00 pm CDT.
The Company plans to meet with the U.S. Food and Drug Administration (FDA) to discuss the development pathway for FG-3246 and anticipates the initiation of the Phase 2 monotherapy dose optimization study of FG-3246 in mCRPC in the second half of 2024.
About the Phase 1b/2 Study of FG-3246 in Combination with Enzalutamide
This Phase 1b/2 study is an investigator-sponsored trial being conducted at the University of California San Francisco to evaluate FG-3246 (FOR46) in combination with enzalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) after prior progression on at least one androgen receptor signaling inhibitor. The primary objective for the Phase 1b portion of the study is to determine the maximally tolerated dose (MTD) and recommended Phase 2 dose of FG-3246 in combination with enzalutamide in patients with mCRPC. The objectives of the Phase 2 portion of the study are to determine the composite response rate (CRR), proportion of participants with a greater than or equal to
About FG-3246
FG-3246 (FOR46) is a potential first-in-class fully human antibody-drug conjugate (ADC), exclusively in-licensed from Fortis Therapeutics, and is being developed by FibroGen for metastatic castration-resistant prostate cancer and potentially other tumor types. FG-3246 binds to an epitope of CD46, a cell receptor target, that induces internalization upon antibody binding, is present at high levels in prostate cancer and other tumor types and demonstrates very limited expression in most normal tissues. FG-3246 is comprised of an anti-CD46 antibody, YS5, linked to the anti-mitotic agent, MMAE, which is a clinically and commercially validated ADC payload. FG-3246 has demonstrated anti-tumor activity in both preclinical and clinical studies. FG-3246 is currently in an ongoing Phase 1b/2 study being conducted at UCSF as an investigator-sponsored trial to evaluate FG-3246 in combination with enzalutamide, and another investigator-sponsored radiopharmaceutical marker trial using a PET with a zirconium tracer for CD46 using the same antibody backbone. The initiation of the Phase 2 monotherapy trial in metastatic castration-resistant prostate cancer is anticipated in the second half of 2024. FG-3246 is an investigational drug and not approved for marketing by any regulatory authority.
About FibroGen
FibroGen, Inc. is a biopharmaceutical company focused on accelerating the development of novel therapies at the frontiers of cancer biology. Pamrevlumab, a fully human anti-CTGF monoclonal antibody, is in clinical development for the treatment of metastatic pancreatic cancer and locally advanced unresectable pancreatic cancer (LAPC). Roxadustat (爱瑞卓®, EVRENZOTM) is currently approved in China, Europe, Japan, and numerous other countries for the treatment of anemia in chronic kidney disease (CKD) patients on dialysis and not on dialysis. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted for review by the China Health Authority. FG-3246 (also known as FOR46), a first-in-class antibody-drug conjugate (ADC) targeting CD46 is in development for the treatment of metastatic castration-resistant prostate cancer. This program also includes the development of an associated CD46-targeted PET biomarker. In addition, FibroGen has expanded its research and development portfolio to include two immuno-oncology product candidates for the treatment of solid tumors. For more information, please visit www.fibrogen.com.
Forward-Looking Statements
This release contains forward-looking statements regarding FibroGen’s strategy, future plans and prospects, including statements regarding FG-3246, its clinical programs and those of its collaboration partner Fortis, and UCSF. These forward-looking statements include, but are not limited to, statements regarding the efficacy, safety, and potential success of FibroGen product candidates, and statements about FibroGen’s plans and objectives and typically are identified by use of terms such as “may,” “will”, “should,” “on track,” “could,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue” and similar words, although some forward-looking statements are expressed differently. FibroGen’s actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties related to the continued progress and timing of its various programs, including the enrollment and results from ongoing and potential future clinical trials, and other matters that are described in FibroGen’s most recent quarterly and annual reports on Form 10-Q and Form 10-K, respectively,as filed with the Securities and Exchange Commission (SEC), including the risk factors set forth therein. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and FibroGen undertakes no obligation to update any forward-looking statement in this press release, except as required by law.
For Investor Inquiries:
David DeLucia, CFA
Vice President of Corporate FP&A / Investor Relations
ir@fibrogen.com
For Media Inquiries:
Meichiel Keenan
Director, Investor Relations and Corporate Communications
media@fibrogen.com
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