cofetuzumab pelidotin (ABBV-647)

P1, N=65, Terminated, AbbVie | Active, not recruiting --> Terminated; Strategic considerations

P1, N=65, Active, not recruiting, AbbVie | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2025 --> May 2026

P1, N=65, Active, not recruiting, AbbVie | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Cofe-P demonstrated a manageable safety profile and preliminary efficacy across NSCLC histologies and EGFR mutation status. These data support PTK7 as a valid therapeutic target for NSCLC.

PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has been investigated in phase I clinical trials for triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer...PTK7 protein and mRNA expression were associated with breast cancer-specific survival of patients with a poor prognostic Nottingham Prognostic Index (NPI) and a moderate prognostic NPI, respectively. Taken together, these data indicate that PTK7 expression is associated with patient outcome in subgroups of breast cancer patients.

P1, N=65, Active, not recruiting, AbbVie | Phase classification: P1b --> P1 | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> Dec 2024

CI, confidence intervals; CBR, clinical benefit rate; CR, complete response; EGFR, epidermal growth factor; mDOR, median duration of response; mPFS, median progression free survival; NSQ, nonsquamous; ORR, objective response rate; PR, partial response; PTK7, protein tyrosine kinase 7; pts, patients; SD, stable disease; WT, wild type. Conclusions Cofe-P was well-tolerated with encouraging antitumor activity observed in rNSCLC and 30% ORR in the subpopulation with NSQ EGFR WT NSCLC and PTK7 ≥90%/≥2+.

P1b, N=65, Active, not recruiting, AbbVie | Trial completion date: Nov 2023 --> Feb 2024 | Trial primary completion date: Nov 2023 --> Feb 2024

When using a potent microtubule inhibitor (Aur0101), PTK7-targeting antibody-drug conjugate (ADC), h6M24-vc0101 (PF-06647020/Cofetuzumab pelidotin) is efficacious only in limited tumor types with low response rates in a phase I trial...MTX-13 displayed a favorable pharmacokinetic and safety profile in monkey with a highest non-severely toxic dose (HNSTD) of >30 mg/kg, significantly higher than 3-5 mg/kg of HNSTD for h6M24-vc0101. The higher therapeutic index of MTX-13 bodes well for its clinical translation with a potential to expand responding patient population beyond that of current PTK7-targeting ADCs.

P1b, N=65, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

The combination of gedatolisib + cofetuzumab pelidotin was well tolerated and demonstrated promising clinical activity. Further investigation of this drug combination in metastatic TNBC is warranted.