Antibody Information
General Information of This Antibody
| Antibody ID | ANTI0FDBOI |
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| Antibody Name | 5F9 |
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| Synonyms |
5F9
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| Antigen Name | Guanylyl cyclase C (GUCY2C) |
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Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
TAK-164 [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | stable disease (SD) |
44%
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| Patients Enrolled |
Inclusion requires GCC+ (H-score ≥10) advanced GI tumors (CRC, gastric/esophageal/pancreatic), ≥18 years, adequate organ function (ANC ≥1.5×10<sup>9</sup>/L, platelets ≥100×10<sup>9</sup>/L, CrCl ≥60 mL/min), ECOG 0-1, and ≥12-week life expectancy. Exclusions: recent anticancer therapy (<28 days), CYP3A/P-gp modulators, bleeding disorders/biopsy contraindications, concurrent alcohol abuse, or other malignancies (exceptions: nonmelanoma skin/carcinoma in situ). For Part C (imaging substudy), ≥2 cm extrahepatic metastasis is required.
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| Administration Dosage |
Adult pts with GCC-positive, advanced/metastatic GI cancers received TAK-164 intravenously on day 1 of a 21-day cycle (Q3W). Dose escalation proceeded based on cycle 1 safety data via a Bayesian model of modified toxicity probability interval starting at 0.004 mg/kg.
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| Related Clinical Trial | |||||
| NCT Number | NCT03449030 | Clinical Status | PHASE1 | ||
| Clinical Description |
An Open-Label, Dose Escalation, Phase 1, First-in-Human Study of TAK-164, an Antibody-Drug Conjugate, in Patients With Advanced Gastrointestinal Cancers Expressing Guanylyl Cyclase C
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| Primary Endpoint |
The study evaluates dose-limiting toxicities (DLTs) based on NCI CTCAE v5, including Grade 4 neutropenia (ANC <500/mm 3), thrombocytopenia (<25,000/mm 3), febrile neutropenia, Grade ≥3 bleeding thrombocytopenia, and Grade ≥3 nausea/vomiting/diarrhea despite optimal care. Adverse event rates (≥Grade 3, drug-related, serious, and leading to discontinuation) were monitored over 22 months, alongside determination of the recommended Phase 2 dose (RP2D).
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| Other Endpoint |
Pharmacokinetics (Cmax, Tmax, AUClast, Ctrough) were assessed over Cycles 1-2, with efficacy endpoints including ORR (CR/PR per modified RECIST v1.1), DCR (CR/PR/SD), DOR, and PFS (PD ≥20% lesion growth or new lesions). ADA positivity was screened over 22 months.
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| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
GCC-positive (H-score10 as indicated by IHC) GI cancers for whom standard treatment was no longer effective, or not available, Eligible GI malignancies included, but were not limited to: metastatic colorectal carcinoma, gastric carcinoma, esophageal carcinoma, small intestine cancer, and pancreatic cancer.
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| Administration Dosage |
TAK-164 as a single intravenous infusion with a duration of up to 2 h, on day 1 of each 21-day cycle or every 3 weeks, until disease progression, unacceptable toxicity, or withdrawal from the study. Doses of 0.004 mg/kg, 0.008 mg/kg, 0.016 mg/kg, 0.032 mg/kg, 0.064 mg/kg, 0.12 mg/kg, 0.16 mg/kg, 0.19 mg/kg, 0.25 mg/kg, and 0.32 mg/kg were planned. To guide dose escalation, a method based on a Bayesian model of modified toxicity probability interval (mTPI) was used.
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| Related Clinical Trial | |||||
| NCT Number | NCT03449030 | Clinical Status | Phase 1 | ||
| Clinical Description |
An open-label, dose escalation, phase 1, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C.
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| Primary Endpoint |
Dosing was capped at 0.19 mg/kg due to hepatic toxicity. The RP2D was determined as 0.064 mg/kg but was considered insufficient to derive significant clinical benefit.
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| Other Endpoint |
No pts had dose-limiting toxicities (DLT) in cycle 1 up to 0.32 mg/kg. TAK-164 appeared to have a manageable safety profile up to 0.064 mg/kg in pts with advanced GI cancers.
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References