cofetuzumab pelidotin (ABBV-647) / Pfizer, AbbVie - LARVOL DELTA

Design and development of biparatopic antibody-drug conjugates against protein tyrosine kinase 7 (AACR 2025) - P1 | "ADCs were produced by conjugating the top biparatopic and monoparatopic antibodies to ZD06519, a topoisomerase 1 inhibitor payload used in ZW191, an ADC targeting FRα under evaluation in a phase 1 clinical trial (NCT06555744). Across multiple cancer cell lines with varying PTK7 expression we compared a lead monoparatopic antibody and cofetuzumab with the top biparatopic antibody which demonstrated greater cell surface decoration and better internalization. At clinically relevant doses, the biparatopic ZD06519 ADC was more efficacious than cofetuzumab pelidotin in triple negative breast cancer and lung cancer cell line derived xenograft models. Additional studies of the PTK7 biparatopic ADC in patient-derived xenograft models and a non-human primate tolerability study are planned."

Breast Cancer • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1 • PTK7

A phase 1b study of cofetuzumab pelidotin monotherapy in patients with PTK7-expressing recurrent non-small cell lung cancer. (PubMed, Lung Cancer) - "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."

Journal • Monotherapy • P1 data • Alopecia • Hematological Disorders • Immunology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PTK7

A phase 1b study of cofetuzumab pelidotin monotherapy in patients with PTK7-expressing recurrent non-small cell lung cancer (Lung Cancer) - P1b | N=65 | NCT04189614 | Sponsor: AbbVie | "Overall, 65 patients received Cofe-P; 51 had PTK7 expression of ≥90 % tumor cells with ≥ 2 + staining intensity by immunohistochemistry. All patients reported adverse events (AEs), most commonly alopecia (52 %) and decreased neutrophil count (43 %); 69 % had grade ≥3 AEs, including grade ≥3 neutropenia in 25 %. Treatment-related AEs were reported in 94 % of patients; none were fatal. Overall, ORR was 18 %; in patients with PTK7 expression of ≥90 % tumor cells with ≥2 + staining and non-squamous epidermal growth factor receptor (EGFR) wild type or mutant, or squamous NSCLC, ORR was 21 %, 15 %, and 13 %, respectively. Overall, median DOR was 7.2 months, median PFS was 5.5 months, and median OS was 12.6 months; longest DOR (median 9.0 months), PFS (median 6.8 months), and OS (median 12.6 months) were in patients with non-squamous EGFR-mutant NSCLC."

P1 data • Non Small Cell Lung Cancer

Preclinical characterization of LY4175408, a novel PTK7 targeting antibody-drug conjugate, utilizing exatecan via a hydrophilic polysarcosine linker platform (EORTC-NCI-AACR 2024) - "A phase I trial investigating cofetuzumab pelidotin, an antibody-drug conjugate (ADC) containing an auristatin microtubule inhibitor, showed efficacy in different tumor types but displayed notable toxicities... LY4175408 is a novel therapeutic candidate for treating PTK7-positive tumors. An IND submission is anticipated for 2025."

Late-breaking abstract • Preclinical • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • PTK7

Protein Tyrosine Kinase 7 (PTK7) in Breast Cancer: A Retrospective Analysis of Tumour Expression and Association with Clinical Outcome. (PubMed, Cancers (Basel)) - "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."

Clinical data • Journal • Retrospective data • Breast Cancer • Colon Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • PTK7

An Efficacy and Safety Study of Cofetuzumab Pelidotin in Participants With PTK7-Expressing, Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=65 | Active, not recruiting | Sponsor: AbbVie | Phase classification: P1b ➔ P1 | Trial completion date: Feb 2024 ➔ Dec 2024 | Trial primary completion date: Feb 2024 ➔ Dec 2024

Phase classification • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PTK7

A novel PTK7-directed antibody-drug conjugate (ADC) PRO1107 demonstrated broad antitumor activity with a promising safety profile in preclinical models (SITC 2023) - "An in-house synthesized analog of cofetuzumab pelidotin, a clinical-stage PTK7-directed DAR4 ADC, was included as the benchmarking agent in key studies. It may also carry an expanded therapeutic index compared to other antitubulin-based ADCs on conventional linker-drug platforms. PRO1107 is a highly exciting novel agent to bring forward to the clinic for the treatment of various solid tumors."

Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • PTK7

Phase Ib study of cofetuzumab pelidotin, an anti-PTK7 antibody-drug conjugate, in patients with PTK7-expressing recurrent non-small cell lung cancer (rNSCLC) (ESMO 2023) - P1, P1b | "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+."

Clinical • IO biomarker • P1 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PTK7

An Efficacy and Safety Study of Cofetuzumab Pelidotin in Participants With PTK7-Expressing, Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=65 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Nov 2023 ➔ Feb 2024 | Trial primary completion date: Nov 2023 ➔ Feb 2024

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PTK7

MTX-13, a novel PTK7-directed antibody-drug conjugate with widened therapeutic index shows sustained tumor regressions for a broader spectrum of PTK7-positive tumors. (PubMed, Mol Cancer Ther) - "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."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PTK7

An Efficacy and Safety Study of Cofetuzumab Pelidotin in Participants With PTK7-Expressing, Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=65 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PTK7

Evaluation of the prevalence of MET and protein tyrosine kinase 7 expression in non-small cell lung cancer to evaluate overlap of ADC antigens. (ASCO 2023) - P2 | "Cofetuzumab pelidotin (ABBV-647), an ADC with a similar composition to Teliso-V, contains an anti-protein tyrosine kinase 7 (PTK7) monoclonal antibody (hu6MO24) conjugated to a microtubule-inhibiting cytotoxin, Aur0101 auristatin, via a cleavable cysteine-reactive linker. MET OE and PTK7 expression by IHC were found to be complementary in patients with non-squamous EGFR WT/unknown NSCLC. About 32% of patients were positive for MET OE or PTK7 expression or both. Data represent patients from a single center and more pre-treatment tissue samples that were viable and available."

Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • PTK7

Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention. (PubMed, Cell Death Dis) - "We performed proteomics analyses upon PTK7 knockdown in OC cells and identified novel downstream effectors such as synuclein-γ (SNCG), SALL2, and PP1γ, and these findings were corroborated in ex vivo primary samples using PTK7 monoclonal antibody cofetuzumab. Furthermore, using high-throughput drug sensitivity testing (525 drugs) we show that targeting PTK7 exhibited synergistic activity with chemotherapeutic agent paclitaxel, CHK1/2 inhibitor prexasertib, and PLK1 inhibitor GSK461364, among others, in OC cells and ex vivo primary samples. Taken together, our study provides unique insight into the function of PTK7, which helps to define its role in mediating aberrant Wnt signaling in ovarian cancer."

Journal • CNS Disorders • Oncology • Ovarian Cancer • Psychiatry • Solid Tumor

An Efficacy and Safety Study of Cofetuzumab Pelidotin in Participants With PTK7-Expressing, Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=60 | Recruiting | Sponsor: AbbVie | Trial completion date: Aug 2023 ➔ Nov 2023 | Trial primary completion date: Oct 2022 ➔ Nov 2023

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Joint Disposition Properties and Comprehensive Pharmacokinetic Characterization of Antibody-Drug Conjugates. (PubMed, AAPS J) - "For instance, the linker stability estimates for PF-06650808, PF-06647020, and PF-06664178 were 0.31, 0.14, and 0.096, respectively, from the JDM-based analyses vs. 0.23, 0.11, and 0.086 by the model-based approach. Additionally, the JDMs were estimated for a number of FDA-approved or otherwise well-documented ADCs, showing their utilities in comparing ADCs in terms of favorable PK characteristics."

Journal • PK/PD data

Antibody-drug conjugate (ADC) joint disposition properties and their clinical utilities for comparative assessments in terms of favorable pharmacokinetic (PK) characteristics. (ASCO 2022) - " The joint disposition metrics representing linker stability (AUCmAb/AUCTab), therapeutic exposure ratio (CLPL/CLADC) and effective drug-antibody ratio (DAR) (AUCCPL/AUCADC), were derived mathematically from a framework of typical ADC designs and verified via modeling approaches using PK data of 3 clinical candidates, an anti-Trop2 ADC (PF-06664178) [King GT, et al. Invest New Drugs 2018;36(5):836-847], an anti-Notch3 ADC (PF-06650808) [Rosen LS, et al. Invest New Drugs 2020;38(1):120-130], and an anti-PTK7 ADC (PF-06647020) [Maitland ML, et al... Three joint disposition metrics were derived for integrated PK characterization of ADCs using conventional PK analytes. Their clinical utilities were explored in assessing among ADCs in terms of favorable PK characteristics. Analyses of additional ADCs may be needed to further validate these metrics for broader usage."

Clinical • PK/PD data • Oncology • NOTCH3

Initial phase I safety study of gedatolisib plus cofetuzumab pelidotin for patients with metastatic triple-negative breast cancer. (PubMed, Clin Cancer Res) - "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."

Journal • P1 data • Anorexia • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • Mucositis • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7 (PTK7), in Advanced Solid Tumors. (PubMed, Clin Cancer Res) - P1 | "This PTK7-targeted ADC demonstrated therapeutic activity in previously treated patients with OvCa, NSCLC, and TNBC at a dose range of 2.1-3.2 mg/kg, supporting further clinical evaluation to refine dose, schedule, and predictive tissue biomarker testing in patients with advanced malignancies."

Journal • P1 data • Alopecia • Breast Cancer • Fatigue • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pain • Solid Tumor • Triple Negative Breast Cancer

Actively Targeted Nanomedicines in Breast Cancer: From Pre-Clinal Investigation to Clinic. (PubMed, Cancers (Basel)) - "Currently, there are 14 nanomedicines that have reached the clinic for the treatment of breast cancer, 4 of which are already approved (Kadcyla, Enhertu, Trodelvy, and Abraxane)...In TNBC these conjugates (Trodelvy, Glembatumumab-Vedotin, Ladiratuzumab-vedotin, Cofetuzumab-pelidotin, and PF-06647263) are directed against various targets, in particular Trop-2 glycoprotein, NMB glycoprotein, Zinc transporter LIV-1, and Ephrin receptor-4, to achieve this selective accumulation, and include campthotecins, calicheamins, or auristatins as drugs. Apart from the antibody-drug conjugates, there are other active targeted nanosystems that have reached the clinic for the treatment of these tumors such as Abraxane and Nab-rapamicyn (albumin nanoparticles entrapping placlitaxel and rapamycin respectively) and various liposomes (MM-302, C225-ILS-Dox, and MM-310) loaded with doxorubicin or docetaxel and coated with ligands targeted to Ephrin A2, EPGF, or HER-2 receptors. In this work,..."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

"Dr. @HosseinBorghaei @FoxChaseCancer discussed ADCs for AXL (Enapotamab Vedotin, BA3001), ROR, and protein tyrosine kinase 7 (PTK7) (PF-06647020) for treatment of #lungcancer at #TTLC22. @lcrf_org" (@EugeneManley)

Lung Cancer • Oncology • Solid Tumor • AXL

Protein tyrosine kinase 7 (PTK7) biomarker analysis in patients (pts) treated with PF-06647020, a PTK7 antibody-drug conjugate (ADC), in a phase I dose expansion study (AACR 2019) - "A novel CLIA validated LDT was developed and implemented to assess PTK7 baseline levels in FFPE tumors from pts treated with PF-06647020. Clinical responses tended to correlate with H-scores that were higher than the mean for each tumor type."

Biomarker • Clinical • P1 data

PF-06647020 (PF-7020), an antibody-drug conjugate (ADC) targeting protein tyrosine kinase 7 (PTK7), in patients (pts) with advanced solid tumors: Results of a phase I dose escalation and expansion study. (ASCO 2018) - P1; "Promising antitumor activity and manageable safety profile of PF-7020 were observed in pts with advanced OVCA, NSCLC and TNBC resistant to SoC. Further investigation of PF-7020 is ongoing."

Clinical • P1 data • Non Small Cell Lung Cancer • Ovarian Cancer • Triple Negative Breast Cancer

[VIRTUAL] A phase 1b, open-label, single-arm study of cofetuzumab pelidotin (a PTK7-targeting antibody-drug conjugate) in patients with PTK7-expressing, recurrent non-small cell lung cancer (NSCLC). (ASCO 2021) - P1b | "Cofetuzumab pelidotin (2.8 mg/kg) is administered intravenously every 3 weeks until the patient experiences disease progression, intolerable toxicity, or other study treatment discontinuation criteria are met . The study commenced on February 13, 2020 and enrollment is ongoing."

Clinical • IO biomarker • P1 data • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] An initial safety study of gedatolisib plus cofetuzumab pelidotin for metastatic triple-negative breast cancer (SABCS 2020) - P1 | "The combination of gedatolisib + cofetuzumab pelidotin for the treatment of metastatic TNBC was found to be well tolerated and demonstrated promising clinical activity. Further investigation of this drug combination in metastatic TNBC is warranted. Trial Registration: NCT03243331"

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Triple Negative Breast Cancer • HER-2

An Efficacy and Safety Study of Cofetuzumab Pelidotin in Participants With PTK7-Expressing, Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1b; N=60; Recruiting; Sponsor: AbbVie; N=40 ➔ 60; Trial completion date: Oct 2022 ➔ Aug 2023

Clinical • Enrollment change • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor