Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0XHZLG
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| ADC Name |
Cofetuzumab pelidotin
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| Synonyms |
cofetuzumab pelidotin; ABBV-647; PF-06647020; PF-7020; h6M24-vc0101
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| Organization |
Stemcentrx (Top20 MNC) (Originator);Pfizer (Top20 MNC)
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| Drug Status |
Phase 1 (discontinued)
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| Drug-to-Antibody Ratio |
4
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| Structure |
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| Antibody Name |
Cofetuzumab
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Antibody Info | ||||
| Antigen Name |
Inactive tyrosine-protein kinase 7 (PTK7)
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Antigen Info | ||||
| Payload Name |
Auristatin 0101 (Aur0101)
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Mc-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Enzymatic Catalysis
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| Combination Type |
pelidotin
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The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | |||
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| Breast cancer |
1 Trials
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| Lung cancer |
2 Trials
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| Ovarian cancer |
1 Trials
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| Unspecific solid tumor |
1 Trials
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Time to Maximum Concentration (Tmax) | 0.25 | h |
Pharmacokinetics Parameters of Cofe-P ADC, N=63.
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[1] |
| Maximum Observed Concentration (Cmax) | 82.6 | ug/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 7790 | ug*h/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 7820 | ug*h/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63, AUCtau.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4782 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Maximum Observed Concentration (Cmax) | 79.8 | ug/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 5834 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Multiple Dose - Cycle 4.
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[2] |
| Maximum Observed Concentration (Cmax) | 92.9 | ug/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Multiple Dose - Cycle 4.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 6541 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Maximum Observed Concentration (Cmax) | 99.7 | ug/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 9858 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Multiple Dose - Cycle 3.
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[2] |
| Maximum Observed Concentration (Cmax) | 114.7 | ug/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Multiple Dose - Cycle 3.
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Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 7790 | ug*h/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 7820 | ug*h/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63, AUCtau.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4782 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Volume of Distribution (Vd) | 3.2 | L |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 5834 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Multiple Dose - Cycle 4.
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[2] |
| Volume of Distribution (Vd) | 2.8 | L |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Multiple Dose - Cycle 4.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 6541 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Volume of Distribution (Vd) | 2.6 | L |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 9858 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Multiple Dose - Cycle 3.
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[2] |
| Volume of Distribution (Vd) | 2.4 | L |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Multiple Dose - Cycle 3.
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Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 7790 | ug*h/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 7820 | ug*h/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63, AUCtau.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4782 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 5834 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Multiple Dose - Cycle 4.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 6541 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 9858 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Multiple Dose - Cycle 3.
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Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 7790 | ug*h/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 7820 | ug*h/mL |
Pharmacokinetics Parameters of Cofe-P ADC, N=63, AUCtau.
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[1] |
| Elimination Half-Life (t1/2) | 3.01 | day |
Pharmacokinetics Parameters of Cofe-P ADC, N=63.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4782 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Clearance (CL) | 0.95 | L/day |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Elimination Half-Life (t1/2) | 3.1 | day |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 5834 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Multiple Dose - Cycle 4.
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[2] |
| Clearance (CL) | 0.75 | L/day |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Multiple Dose - Cycle 4.
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[2] |
| Elimination Half-Life (t1/2) | 4 | day |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q3W), in patients with solid tumors, Multiple Dose - Cycle 4.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 6541 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Clearance (CL) | 0.74 | L/day |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Elimination Half-Life (t1/2) | 2.7 | day |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Single Dose - Cycle 1.
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[2] |
| Area Under the Concentration-Time Curve (AUC) | 9858 | ug*h/mL |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Multiple Dose - Cycle 3.
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[2] |
| Clearance (CL) | 0.49 | L/day |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Multiple Dose - Cycle 3.
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[2] |
| Elimination Half-Life (t1/2) | 3.6 | day |
PK parameters of PF-06647020 following single or multiple-dose IV administration (2.8 mg/kg Q2W), in patients with solid tumors, Multiple Dose - Cycle 3.
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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 | [3] | ||||
| Efficacy Data | Partial Response (PR) |
16.67%
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| Patients Enrolled |
Metastatic TNBC or ER low (ER and PgR <5%, HER2 negative) breast cancer, and had received at least one prior chemotherapy for metastatic disease.
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| Administration Dosage |
Gedatolisib 110 mg weekly + cofetuzumab pelidotin 1.4 mg/kg every 3 weeks, 180 mg + 1.4 mg/kg, and 180 mg + 2.8 mg/kg.
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| Related Clinical Trial | |||||
| NCT Number | NCT03243331 | Clinical Status | Phase 1 | ||
| Clinical Description | An initial safety study of gedatolisib plus PTK7-ADC for metastatic triple-negative breast cancer. | ||||
| Primary Endpoint |
A total of 18 pts were enrolled in three dose cohorts: gedatolisib 110 mg weekly cofetuzumab pelidotin 1.40 mg/kg every 3 weeks (n=4), 180 mg, 1.40 mg/kg (n=3), and 180 mg, 2.80 mg/kg (n=11). Nausea, anorexia, fatigue, and mucositis were common but rarely reached grade 3 severity. Myelosuppression was uncommon. ORR was 16.67% (3/18). An additional 3 pts had stable disease (of these 2 had stable disease for>18 weeks); CB18 was 27.80%. Median PFS was 2.00 months (95% confidence interval for PFS: 1.20-6.20). Pts with clinical benefit were enriched with genomic alterations in the PI3K and PTK7 pathways.
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| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
27.00
16.00 21.00 26.00 33.00 % |
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| Patients Enrolled |
Locally advanced or metastatic solid tumors resistant to standard therapy or with no available standard therapy, and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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| Administration Dosage |
Intravenously every 3 weeks at 0.20-3.70 mg/kg or every 2 weeks at 2.10-3.20 mg/kg.
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| Related Clinical Trial | |||||
| NCT Number | NCT02222922 | Clinical Status | Phase 1 | ||
| Clinical Description | A first-in-human phase 1, dose escalation, safety and pharmacokinetic study of PF-06647020 in adult patients with advanced solid tumors. | ||||
| Primary Endpoint |
The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia,fatigue, headache, neutropenia, and vomiting (45%); 25% of patients had grade 3 neutropenia. Two patients experienced doselimiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.80 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27.00% in ovarian cancer (n=63), 19% in NSCLC (n=31), and 21% in TNBC (n=29).
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| Experiment 3 Reporting the Activity Date of This ADC | [5] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT04189614 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1b efficacy and safety study of cofetuzumab pelidotin (ABBV-647, a PTK7-targeting antibody drug conjugate) in subjects with PTK7-expressing, recurrent non-small cell lung cancer. | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
30%
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| Patients Enrolled |
Inclusion criteria for Q3W: advanced/metastatic solid tumors refractory to standard therapy, ECOG PS 0-1, adequate organ function; Part 2 targeted ovarian cancer (OVCA), TNBC, and NSCLC. Q2W included platinum-resistant OVCA (≤2 prior lines) or recurrent NSCLC (≤3 prior lines), ECOG PS 0-2. Exclusions: non-epithelial OVCA, active CNS metastases, unresolved bowel obstruction, recent anticancer therapy (4 weeks), or active infections. Both regimens excluded patients with significant comorbidities (uncontrolled infections, recent major surgery/radiation).
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| Administration Dosage |
Investigational drug infused over 60 minutes once every 21 days, Investigational drug infused over 60 minutes once every 14 days (28 day cycle).
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| Related Clinical Trial | |||||
| NCT Number | NCT02222922 | Clinical Status | PHASE1 | ||
| Clinical Description | A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647020 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS | ||||
| Primary Endpoint |
This section details safety assessments for PF-06647020 across Q3W (every 3 weeks) and Q2W (every 2 weeks) regimens, monitoring dose-limiting toxicities (DLTs) during initial treatment cycles (21 days for Q3W, 28 days for Q2W) including hematologic (Grade 4 neutropenia, febrile neutropenia), hepatic (Grade ≥3 bilirubin/transaminases), and non-hematologic toxicities. Treatment-emergent adverse events (AEs), graded per NCI CTCAE v4.03, were tracked for up to 32 months (Q3W) or 19 months (Q2W), with lab abnormalities (hematology, chemistry, urinalysis, coagulation) analyzed for shifts from baseline to Grade ≥3.
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| Other Endpoint |
Pharmacokinetic (PK) parameters (AUCtau, Cmax, CL, Vss, t1/2, Rac, Tmax, AUClast, AUCinf) were evaluated for PF-06647020, its metabolites (PF-06380101, hu6M024 mAb), and dose-normalized values in DDI sub-studies under Q3W (504-hour tau) and Q2W (336-hour tau) regimens. Efficacy endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), time to progression (TTP), and progression-free survival (PFS), assessed per RECIST v1.1 via tumor imaging every 6-8 weeks. Immunogenicity (anti-drug antibodies [ADA]/neutralizing antibodies [NAb]) was monitored for ~31 months (Q3W) or 18 months (Q2W).
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| Experiment 5 Reporting the Activity Date of This ADC | [7] | ||||
| Patients Enrolled |
Inclusion criteria require histologically confirmed PTK7-expressing NSCLC, progression after platinum-based therapy +/- targeted agents (≤2 prior lines [≤3 if targeted]), ECOG 0-1, measurable disease, and adequate organ function. Exclusions include active CNS metastases (unless treated/asymptomatic for ≥2 weeks), unresolved Grade ≥2 toxicity (except alopecia/anaemia), significant comorbidities, recent anticancer therapy (within 28 days, except palliative RT ≤10 fractions), or herbal therapies within 7 days.
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| Administration Dosage |
Participants will receive 2.8mg/kg of cofetuzumab pelidotin by IV every 3 weeks
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| Related Clinical Trial | |||||
| NCT Number | NCT04189614 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1b Efficacy and Safety Study of Cofetuzumab Pelidotin (ABBV-647, a PTK7-Targeting Antibody Drug Conjugate) in Subjects With PTK7-Expressing, Recurrent Non-Small Cell Lung Cancer | ||||
| Primary Endpoint |
The primary efficacy endpoint is Objective Response Rate (ORR), measured up to 3 years, defined as the percentage of participants achieving confirmed complete response (CR) or partial response (PR) per RECIST v1.1.
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| Other Endpoint |
Secondary endpoints include Duration of Response (DOR) (time from initial response to progression/death), Progression-Free Survival (PFS) (time from first dose to progression/death), and Overall Survival (OS) (time from first dose to death from any cause), all assessed over ~3 years.
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References