Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ID: DRG0QMIBK)
| ADC Name |
FOR46
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| Synonyms |
FOR46; FG-3246
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| Organization |
University of California, San Francisco (Originator);Kyntra Bio;Fortis Therapeutics
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| Drug Status |
Phase 2
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| Drug-to-Antibody Ratio |
3.7
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| Structure |
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| Antibody Name |
YS5
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Antibody Info | ||||
| Antigen Name |
Membrane cofactor protein (CD46)
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Antigen Info | ||||
| Payload Name |
Monomethyl auristatin E
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Payload Info | ||||
| Payload Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
A cleavable linker
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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2027 Update
The disease landscape of This ADC
2027 Update
The clinical trial pipelines of This ADC
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
20%
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| Patients Enrolled |
Inclusion: Men ≥18 with histologically confirmed mCRPC (progressing post-ARSI therapy), castrate testosterone (<50 ng/dL), ECOG 0-1, adequate organ function, and willingness for biopsy (dose expansion). Exclusion: Persistent toxicity (Grade≥2 neuropathy), prior mCRPC chemotherapy (hormone-sensitive >6 months prior allowed), recent therapy/surgery (≤28 days), uncontrolled comorbidities (cardio/pulmonary/CNS metastases), active HIV/HepB/C, or CYP3A4 modulators. Dose escalation excludes episodic atrial fibrillation history.
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| Administration Dosage |
FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46
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| Related Clinical Trial | |||||
| NCT Number | NCT03575819 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1 Study of FOR46 Administered Every 21 Days in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) | ||||
| Primary Endpoint |
Safety assessments include toxicity evaluation (type, incidence, severity, relatedness) and dose-limiting toxicities (DLTs) through 1-month post-treatment, along with disease response (≥50% PSA decline and objective response per RECIST criteria) assessed over 12 months.
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| Other Endpoint |
Pharmacokinetics focus on FOR46 plasma concentration (Cmax, AUC, half-life), antidrug antibody levels, and median radiographic progression-free survival (rPFS) at 12 months per PCWG3 criteria, monitored for 1 month post-dosing.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Inclusion: RRMM patients (≥18 years) refractory/intolerant to PI, IMiD, and CD38 therapy; ECOG 0-1; adequate organ function; contraception compliance. Exclusion: Persistent toxicity (Grade≥2 neuropathy), recent therapy/transplant/surgery (12-28 days), uncontrolled comorbidities (cardio/pulmonary/infectious), CYP3A4 modulators, warfarin use, atrial fibrillation history, or prior MMAE/MMAF ADC exposure. Breastfeeding excluded.
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| Administration Dosage |
FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46
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| Related Clinical Trial | |||||
| NCT Number | NCT03650491 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase I Study of FOR46 Administered Every 21 Days in Patients With Relapsed or Refractory Multiple Myeloma (RRMM) | ||||
| Primary Endpoint |
Safety evaluation includes monitoring treatment-related adverse events by NCI CTCAE v5.0 and dose-limiting toxicities through 1-month post-treatment. Efficacy is measured by overall response rate (≥PR/CR/stringent CR/MRD negativity) at 6 months.
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| Other Endpoint |
Pharmacokinetic analysis assesses FOR46 plasma concentration (Cmax, AUC, elimination half-life), antidrug antibody levels up to 1 month post-treatment, and treatment response (duration, progression-free survival, time to progression) via IMWG criteria over 6 months.
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| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Inclusion: Histologically confirmed prostate adenocarcinoma (excluding small cell/neuroendocrine) with mCRPC progression post-ARSI (abiraterone/enzalutamide/apalutamide/darolutamide); castrate testosterone (<50 ng/dL); ≥1 measurable metastasis; adequate organ function. Biopsy (fresh/archival ≤1 year) required for CD46 IHC. Exclusion: Prior CD46-targeted therapy, non-adenocarcinoma histology, >1 prior ARSI, recent anticancer therapy/radiation (≤28 days), actionable mutations (unless treated/progressed), prior chemotherapy (except 1 taxane in castration-sensitive setting >12 months prior), hypersensitivity to FG-3246/antibodies, malignancy (≤5 years, excluding treated skin cancers), or strong CYP3A4 modulators.
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| Administration Dosage |
FG-3246 will be administered per schedule specified in the arm description.
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| Related Clinical Trial | |||||
| NCT Number | NCT06842498 | Clinical Status | PHASE2 | ||
| Clinical Description | A Phase 2 Dose Optimization Trial Evaluating a CD46-Targeted Antibody-Drug Conjugate (FG-3246) in Patients With Metastatic Castration-Resistant Prostate Cancer | ||||
| Primary Endpoint |
The study evaluates radiographic progression-free survival (rPFS) per RECIST v1.1 and PCWG3 criteria until progression (up to ~31 months), along with treatment-emergent adverse events (TEAEs) and pharmacokinetic parameters (Cmax of FG-3246, CD46 antibody, and free MMAE) across 21-day cycles. Safety monitoring continues until 28 days after the last dose.
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| Other Endpoint |
Efficacy assessments include 6- and 12-month rPFS rates, confirmed ORR, duration of response (DoR), PSA50/90 response rates, composite response (CRR), PSA-PFS, disease control (DCR), clinical benefit (CBR), time to symptomatic skeletal events (SSRE), and overall survival (OS) up to ~31 months. Immunogenicity (ADA/NAb development) is also tracked throughout treatment and post-dosing.
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| Experiment 4 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Inclusion: Men ≥18 with mCRPC (progressed post-ARSIs, no prior mCRPC taxane, PSA≥2 ng/mL or measurable disease), castrate testosterone (<50 ng/dL), ECOG≤1, adequate organ function, and biopsy/PET imaging (expansion phase). Exclusion: Prior CD46 therapy, recent radiation/systemic therapy (<14 days), small-cell histology, uncontrolled cardiac/pulmonary/CNS conditions, CYP3A4 inhibitors, or active infections.
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| Administration Dosage |
A 3+3 dose escalation design was utilized with a starting dose of FOR46 of 1.8 mg/kg adjusted body weight (ABW) in combination with enza 160 mg/day. Dose escalation was explored with and without prophylactic granulocyte colony-stimulating factor (G-CSF) support.
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| Related Clinical Trial | |||||
| NCT Number | NCT05011188 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase 1b/2 Study of FOR46 in Combination With Enzalutamide in Patients With Metastatic Castration Resistant Prostate Cancer | ||||
| Primary Endpoint |
The Phase 1b trial evaluates the maximum tolerated dose (MTD) of FOR46 over 3 weeks by dose-escalation with cohorts of 3+3/6 patients-dose-limiting toxicities (DLTs, per CTCAE v5.0) determine escalation (stopped if ≥2/3-6 patients experience DLTs). Phase 2 assesses composite response rate (CRR; ≥50% PSA decline + RECIST 1.1 response) over 2 years with 95% CIs.
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| Other Endpoint |
Efficacy endpoints include PSA50 (≥50% PSA decline), ORR (RECIST 1.1), duration of response, time to PSA progression, rPFS (PCWG3), and median overall survival (Kaplan-Meier, 2-year follow-up). Safety tracks AE frequency/severity (CTCAE v5.0).
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| Experiment 5 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Partial Response (PR) |
22.20%
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| Patients Enrolled |
Metastatic castration-resistant prostate cancer (CRPC).
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| Administration Dosage |
Intravenous FOR46 on day 1 of every 21-day cycle. Dose levels ranged from 0.10 mg/kg. the starting dose level, to 3.00 mg/kg. The trial established 2.70 mg/kg to be the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of the agent.
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| Related Clinical Trial | |||||
| NCT Number | NCT03575819 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1 study of FOR46 administered every 21 days in patients with metastatic castration-resistant prostate cancer (mCRPC). | ||||
| Primary Endpoint |
MtD and phase 1b dose=2.70 mg/kg.
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| Other Endpoint |
18 pts had measurable lesions; 8 of 18 (44.44%) had tumor regression, with 4 (22.22%) confirmed partial responses (PR). The median duration of response is > 14 wks (range 9 -31+ weeks).
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| Experiment 6 Reporting the Activity Date of This ADC | [6] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT05011188 | Clinical Status | Phase 1/2 | ||
| Clinical Description | A phase 1b/2 study of FOR46 in combination with enzalutamide in patients with metastatic castration resistant prostate cancer. | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [7] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT03650491 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1 study of FOR46 administered every 21 days in patients with relapsed or refractory multiple myeloma (RRMM). | ||||
References