Kyntra Bio's FG-3246 ADC Shows Promising Results in Metastatic Prostate Cancer Combination Trial
Key Insights
Kyntra Bio (search)'s FG-3246 antibody-drug conjugate combined with enzalutamide achieved a median radiographic progression-free survival of 10.1 months in patients with metastatic castration-resistant prostate cancer (search) who had progressed on only one prior androgen receptor pathway inhibitor.
The Phase 1b/2 investigator-sponsored trial demonstrated a composite response rate of 21% in the overall cohort of 44 patients and 40% in patients with limited prior treatment exposure.
Higher tumor uptake of companion diagnostic FG-3180 showed a trend toward improved PSA50 response rates (p=0.053), supporting its potential as a patient selection biomarker.
Kyntra Bio (search) announced positive results from an investigator-sponsored Phase 1b/2 study evaluating FG-3246, a first-in-class CD46 (search)-targeting antibody-drug conjugate, in combination with enzalutamide for patients with metastatic castration-resistant prostate cancer (search) (mCRPC). The data, presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium, showed encouraging anti-tumor activity particularly in patients with limited prior treatment exposure.
Clinical Efficacy Results
The study enrolled 44 biomarker unselected patients with progressive mCRPC, with 17 patients participating in the Phase 1b dose escalation portion. All patients had progressed on at least one prior androgen receptor pathway inhibitor (ARPI), while those who received prior chemotherapy in the castration-resistant setting were excluded. Notably, over 60% of patients had progressed on two or more prior ARPIs, including prior enzalutamide treatment.
FG-3246 combined with enzalutamide demonstrated a composite response rate of 21% in the overall cohort and 40% in patients who had progressed on only one prior ARPI. The median radiographic progression-free survival (rPFS) was 7.0 months in the overall cohort, with a particularly encouraging median rPFS of 10.1 months observed in patients who had progressed on only one prior ARPI. This result remained consistent across different prior ARPIs administered.
Biomarker Development
A significant finding emerged regarding FG-3180, a CD46 (search)-directed PET imaging agent that serves as a companion diagnostic. Higher tumor uptake of FG-3180 demonstrated a trend towards higher probability of PSA50 response (p=0.053), highlighting its potential as a biomarker for patient selection in future trials.
"The positive trend observed in the association between tumor uptake of FG-3180 (CD46 (search)-targeting PET) and PSA50 response, though from a small number of patients, is especially intriguing and I'm excited to see the potential utility of this biomarker further explored in the Phase 2 monotherapy study," commented Dr. Rahul Aggarwal, Professor of Medicine at the University of California San Francisco and Principal Investigator of the study.
Safety Profile and Dosing
The Phase 1b dose escalation determined the recommended Phase 2 dose as 2.1 mg/kg of FG-3246 and 160 mg/day of enzalutamide. The combination therapy demonstrated a similar safety profile to the previous Phase 1 monotherapy trial of FG-3246. Neutropenia risk was successfully mitigated with G-CSF prophylaxis, addressing a key safety concern from earlier studies.
The most frequent treatment-related adverse events included fatigue, peripheral neuropathy, anorexia, and dysgeusia. While cumulative toxicities, including peripheral neuropathy, led to treatment discontinuation for some patients, the overall safety profile remained manageable.
Drug Mechanism and Development
FG-3246 is a fully human antibody-drug conjugate exclusively in-licensed from Fortis Therapeutics (search). The drug binds to an epitope of CD46 (search), a cell receptor target that induces internalization upon antibody binding and is present at high levels in prostate cancer and other tumor types while demonstrating very limited expression in most normal tissues. FG-3246 comprises an anti-CD46 antibody, YS5, linked to the anti-mitotic agent MMAE, a clinically and commercially validated ADC payload.
Future Development Plans
The results validate key design elements of Kyntra Bio (search)'s ongoing Phase 2 monotherapy trial of FG-3246, most importantly the inclusion of patients who have progressed on only one prior ARPI and integration of baseline FG-3180 PET for all enrolled patients. The Phase 2 monotherapy trial is on track for interim analysis in the second half of 2026.
"The 10.1 months of median rPFS observed in patients progressing on only one prior ARPI, and the mitigation of neutropenia related adverse events with prophylactic G-CSF are especially encouraging as they further validate our Phase 2 monotherapy trial design," said Thane Wettig, Chief Executive Officer of Kyntra Bio (search).
The ongoing Phase 2 monotherapy trial will further assess the correlation between CD46 (search) expression and response to FG-3246, while evaluating the potential of FG-3180 to serve as a biomarker for patient selection in future trials.