FibroGen Announces Publication of Results from Phase 1 Monotherapy Study of FG-3246 in Patients with Metastatic Castration-Resistant Prostate Cancer in the Journal of Clinical Oncology
FibroGen (NASDAQ: FGEN) announced the publication of Phase 1 trial results for FG-3246, a first-in-class anti-CD46 antibody drug conjugate, in treating metastatic castration-resistant prostate cancer (mCRPC). The study, involving 56 heavily pre-treated patients, demonstrated promising results:
Key findings include:
- Maximally tolerated dose: 2.7 mg/kg every 3 weeks
- 20% confirmed objective response rate with 7.5-month median duration
- 80% disease control rate
- 36% PSA50 response rate in 39 evaluable patients
- 8.7-month median radiographic progression-free survival
The company plans to initiate a Phase 2 monotherapy dose optimization study by mid-2025, with topline results from a combination trial with enzalutamide expected in the second half of 2025.
FibroGen (NASDAQ: FGEN) ha annunciato la pubblicazione dei risultati della fase 1 dello studio per FG-3246, un coniugato di anticorpo anti-CD46 di prima classe, per il trattamento del carcinoma prostatico metastatico resistente alla castrazione (mCRPC). Lo studio, che ha coinvolto 56 pazienti con precedenti trattamenti intensivi, ha mostrato risultati promettenti:
I risultati chiave includono:
- Dosaggio massimo tollerato: 2,7 mg/kg ogni 3 settimane
- 20% di tasso di risposta obiettiva confermata con una durata mediana di 7,5 mesi
- 80% di tasso di controllo della malattia
- 36% di tasso di risposta PSA50 in 39 pazienti valutabili
- 8,7 mesi di sopravvivenza libera da progressione radiografica mediana
L'azienda prevede di avviare uno studio di ottimizzazione del dosaggio della monoterapia di fase 2 entro metà del 2025, con risultati preliminari attesi da uno studio combinato con enzalutamide nella seconda metà del 2025.
FibroGen (NASDAQ: FGEN) anunció la publicación de los resultados del ensayo de fase 1 para FG-3246, un conjugado de anticuerpo anti-CD46 de primera clase, en el tratamiento del cáncer de próstata metastásico resistente a la castración (mCRPC). El estudio, que involucró a 56 pacientes con tratamientos previos intensivos, demostró resultados prometedores:
Los hallazgos clave incluyen:
- Dosis máxima tolerada: 2,7 mg/kg cada 3 semanas
- 20% de tasa de respuesta objetiva confirmada con una duración mediana de 7,5 meses
- 80% de tasa de control de la enfermedad
- 36% de tasa de respuesta PSA50 en 39 pacientes evaluables
- 8,7 meses de supervivencia libre de progresión radiográfica mediana
La empresa planea iniciar un estudio de optimización de dosis de monoterapia de fase 2 para mediados de 2025, con resultados preliminares de un ensayo combinado con enzalutamida esperados para la segunda mitad de 2025.
FibroGen (NASDAQ: FGEN)은 전이성 거세 저항성 전립선암(mCRPC) 치료를 위한 최초의 항-CD46 항체 약물 결합체인 FG-3246의 1상 시험 결과 발표를 알렸습니다. 56명의 중증 전처치 환자를 포함한 이 연구는 유망한 결과를 보여주었습니다:
주요 발견 내용은 다음과 같습니다:
- 최대 허용 용량: 2.7 mg/kg 매 3주마다
- 확인된 객관적 반응률 20% 및 중앙 지속 기간 7.5개월
- 질병 조절률 80%
- 39명의 평가 가능한 환자에서 PSA50 반응률 36%
- 중앙 방사선 진행 없는 생존 기간 8.7개월
회사는 2025년 중반까지 2상 단독 요법 용량 최적화 연구를 시작할 계획이며, 2025년 하반기에는 엔잘루타미드와의 병용 시험에서의 주요 결과가 예상됩니다.
FibroGen (NASDAQ: FGEN) a annoncé la publication des résultats de l'essai de phase 1 pour FG-3246, un conjugué d'anticorps anti-CD46 de première classe, dans le traitement du cancer de la prostate métastatique résistant à la castration (mCRPC). L'étude, impliquant 56 patients fortement prétraités, a démontré des résultats prometteurs :
Les résultats clés comprennent :
- Posologie maximale tolérée : 2,7 mg/kg toutes les 3 semaines
- Taux de réponse objective confirmé de 20 % avec une durée médiane de 7,5 mois
- Taux de contrôle de la maladie de 80 %
- Taux de réponse PSA50 de 36 % chez 39 patients évaluables
- Surrénale médiane de 8,7 mois sans progression radiographique
L'entreprise prévoit de lancer une étude d'optimisation de la dose de monothérapie de phase 2 d'ici mi-2025, avec des résultats préliminaires d'un essai combiné avec l'enzalutamide attendus dans la seconde moitié de 2025.
FibroGen (NASDAQ: FGEN) gab die Veröffentlichung der Ergebnisse der Phase-1-Studie für FG-3246, ein Antikörper-Wirkstoff-Konjugat der ersten Klasse gegen CD46 zur Behandlung von metastasiertem kastrationsresistentem Prostatakrebs (mCRPC), bekannt. Die Studie, an der 56 stark vorbehandelte Patienten teilnahmen, zeigte vielversprechende Ergebnisse:
Wichtige Ergebnisse umfassen:
- Maximal tolerierte Dosis: 2,7 mg/kg alle 3 Wochen
- 20% bestätigte objektive Ansprechrate mit einer medianen Dauer von 7,5 Monaten
- 80% Krankheitskontrollrate
- 36% PSA50-Ansprechrate bei 39 bewertbaren Patienten
- Median von 8,7 Monaten progressionsfreier Überlebenszeit nach radiologischen Kriterien
Das Unternehmen plant, bis Mitte 2025 eine Phase-2-Studie zur Dosisoptimierung der Monotherapie zu starten, wobei die Ergebnisse einer Kombinationstherapie mit Enzalutamid für die zweite Hälfte von 2025 erwartet werden.
- First-in-class anti-CD46 treatment showing promising efficacy in heavily pre-treated patients
- 20% confirmed objective response rate with 7.5-month duration
- 80% disease control rate with 48% of patients exceeding 24 weeks treatment
- Favorable safety profile with fewer ocular events compared to similar treatments
- 80% of baseline tumors showed positive CD46 expression
- Significant adverse events including 48.2% infusion reactions
- 41.1% of patients experienced neutropenia
- 32.1% of patients developed peripheral neuropathy
- Phase 2 trial not starting until mid-2025
Insights
The publication of FG-3246's Phase 1 data in the Journal of Clinical Oncology represents a meaningful clinical milestone for FibroGen's oncology pipeline. The data shows
What's noteworthy is FG-3246's novel mechanism as a CD46-targeting antibody-drug conjugate, representing a different approach than PSMA-targeted therapies currently dominating the prostate cancer ADC landscape. The
The safety profile appears manageable with anticipated MMAE-related toxicities like neutropenia (
Particularly interesting is the translational data showing CD46 expression in
With Phase 2 monotherapy and combination studies with enzalutamide advancing in 2025, FG-3246 represents a potentially important addition to the metastatic castration-resistant prostate cancer treatment landscape where novel approaches remain urgently needed despite recent therapeutic advances.
This Phase 1 data publication represents a positive development for FibroGen's oncology pipeline diversification strategy. For a micro-cap company (
The decision to advance FG-3246 into Phase 2 by mid-2025 signals management confidence in the asset's potential, while the planned combination study with enzalutamide (with results expected 2H 2025) could potentially enhance the value proposition through combination approaches.
From a market perspective, the metastatic castration-resistant prostate cancer space represents a substantial commercial opportunity, with existing ADC therapies demonstrating strong uptake. A differentiated mechanism targeting CD46 rather than PSMA could potentially address patients who don't respond to current approaches.
The publication in a high-impact journal adds scientific credibility and increases visibility among potential partners. For investors, this program provides a diversification opportunity beyond FibroGen's historical focus.
While still early-stage with significant development milestones ahead, the promising clinical activity in a heavily pre-treated population and clear development roadmap for 2025 represent tangible progress for a company of FibroGen's size. The positive data supports continued investment in the program and maintains optionality for future partnership opportunities as the asset advances through clinical development.
- FG-3246 showed encouraging anti-cancer activity with an acceptable safety profile in patients with metastatic castration-resistant prostate cancer
- Initiation of Phase 2 monotherapy dose optimization study of FG-3246 in mCRPC expected by mid-2025
SAN FRANCISCO, March 28, 2025 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ: FGEN) today announced the peer-reviewed publication titled “A Phase 1, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients with Metastatic Castration Resistant Prostate Cancer” in the Journal of Clinical Oncology. The manuscript includes the complete results from the Fortis Therapeutics-sponsored Phase 1 study of FOR46 (now known as FG-3246), a potential first-in-class anti-CD46 antibody drug conjugate (ADC) with an MMAE-containing payload, in patients with metastatic castration-resistant prostate cancer (mCRPC).
“I am excited to see the results from the Phase 1 monotherapy study of FOR46 (FG-3246) published in the Journal of Clinical Oncology. This is the first clinical trial targeting CD46 in patients with prostate cancer, and the totality of the data highlights the promising potential of FG-3246 anti-cancer activity, especially when considering the unselected, heavily pre-treated patient population in the trial. The trial results provide key insights into the potential clinical impact of targeting CD46 in the treatment of mCRPC and support its further development in this disease space with high unmet need,” said Dr. Rahul Aggarwal, Professor of Medicine at the University of California San Francisco, and Principal Investigator of the study.
“We are looking forward to advancing FG-3246 in the clinic and remain on track for initiating the Phase 2 monotherapy study by mid-2025 as well as disclosing topline results from the combination trial of FG-3246 and enzalutamide in the second half of 2025,” added Thane Wettig, Chief Executive Officer of FibroGen. “FG-3246 represents a potential first-in-class, non-PSMA approach to treating mCRPC and we, along with the medical community, are excited about the potential for CD46 to become a next generation target in the prostate cancer treatment paradigm.”
This Phase 1 study was a multi-center, first-in-human, open label dose escalation and expansion study evaluating the 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. Notably, patients were biomarker unselected and heavily pre-treated, having received a median of 5 lines of therapy prior to receiving FG-3246.
Key highlights from the publication include:
- The maximally tolerated dose of FG-3246 was 2.7 mg/kg by adjusted body weight (AjBW) every 3 weeks
- The most frequent adverse events were consistent with other MMAE-based ADCs and included infusion related reactions (
48.2% ), neutropenia (41.1% ), and peripheral neuropathy (32.1% ).- Ocular adverse events were infrequent, which may be a distinguishing feature compared with other MMAE-based ADCs
- Efficacy observed in the RECIST-evaluable set of 25 patients:
- Confirmed objective response rate was
20% with median duration of response of 7.5 months- All objective responses observed at a starting dose of 2.7 mg/kg or higher
- Disease control rate was
80% with duration of treatment exceeding 24 weeks in 12 patients (48% )
- Confirmed objective response rate was
- PSA50 response rate of
36% in 39 evaluable patients- Of eight evaluable patients who received docetaxel in the castration-sensitive setting, four (
50% ) achieved a confirmed PSA50 response
- Of eight evaluable patients who received docetaxel in the castration-sensitive setting, four (
- Median radiographic progression-free survival of 8.7 months in all 40 subjects in the efficacy analysis set
- Of 15 evaluable baseline tumors, 12 (
80% ) were positive for CD46 expression by immunohistochemistry - FG-3246 responders were found to have a significantly higher frequency of effector T cells and lower frequency of immunosuppressive myeloid cells
The Company anticipates initiating the Phase 2 monotherapy dose optimization study of FG-3246 in patients with mCRPC by mid-2025.
FG-3246 is also being evaluated in combination with enzalutamide in an investigator-sponsored study with topline results from the Phase 2 portion of the study anticipated in 2H 2025.
About the Phase 1 Study
FOR46-001 (NCT03575819) is a Phase 1, dose-escalation study sponsored by Fortis Therapeutics to evaluate multiple doses of IV-administered FG-3246 (also known as FOR46) in patients with mCRPC who have progressive disease on at least one ARSI, followed by a dose-expansion cohort, to evaluate the safety, tolerability, PK, biological activity, and preliminary evidence of anti-tumor activity of FG-3246 in this patient population.
Thirty-three (33) patients were enrolled in the dose-escalation phase of the study at doses between 0.1 mg/kg and 3.0 mg/kg every three weeks (Q3W), with adjusted body weight dosing (AjBW) used at most dose levels above 2.1 mg/kg. Safety and tolerability of FG-3246 were evaluated in the dose-escalation period of the study.
Twenty-three (23) patients were enrolled in the dose-expansion period of the study; 18 patients with adenocarcinoma mCRPC (Cohort 1) and five patients with neuroendocrine prostate cancer (Cohort 2). All patients in the expansion cohorts were treated at 2.7 mg/kg AjBW to a maximum of 270 mg every three weeks.
The safety profile of FG-3246 was characterized, and anti-tumor activity of FG-3246 in adenocarcinoma patients dosed at ≥ 1.2 mg/kg was evaluated.
About Metastatic Castration-Resistant Prostate Cancer
Prostate cancer is the second most common malignancy in men, contributing significantly to male mortality rates. Approximately
About FG-3246
FG-3246 (also known as 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 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 1/2 study being conducted at UCSF to evaluate it in combination with enzalutamide with topline data from the Phase 2 portion of the study expected in the second half of 2025, and a biomarker trial using a PET biomarker for CD46 using the same antibody backbone. We anticipate the initiation of the Phase 2 monotherapy dose optimization trial in metastatic castration-resistant prostate cancer by mid-2025. 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 development of novel therapies at the frontiers of cancer biology and anemia. 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. The Company continues to evaluate a development plan for roxadustat in anemia associated with lower-risk myelodysplastic syndrome (LR-MDS) in the U.S. 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 FG-3180, an associated CD46-targeted PET biomarker. 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 its commercial products and clinical programs and those of its collaboration partners Fortis and UCSF. These forward-looking statements include, but are not limited to, statements regarding the efficacy, safety, and potential clinical or commercial success of FibroGen products and product candidates, and statements about FibroGen’s plans and objectives. These forward-looking statements are typically 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 Annual Report on Form 10-K for the most recent fiscal year, and any more recent Quarterly Reports on Form 10-Q, each 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.
References:
1. Seer.cancer.gov https://seer.cancer.gov/statfacts/html/prost.html
For Investor Inquiries:
David DeLucia, CFA
Senior Vice President and Chief Financial Officer
ir@fibrogen.com
