A Phase 1 Dose-Escalation Study of PF-06671008, a Bispecific T-Cell-Engaging Therapy Targeting P-Cadherin in Patients With Advanced Solid Tumors

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 May 2

PMID 35493516

Authors

James J Harding

Ignacio Garrido-Laguna

Xiaoying Chen

Cynthia Basu

Afshin Dowlati

Alison Forgie

Andrea T Hooper

Cris Kamperschroer

Steven I Max

Allison Moreau

Megan Shannon

Gilbert Y Wong

David S Hong

Affiliations

Soon will be listed here.

Abstract

Clinical Trial Registration: URL: https://clinicaltrials.gov/ct2/show/NCT02659631, ClinicalTrials.gov Identifier: NCT02659631.

Citing Articles

Oncology Clinical Trials Targeting Members of the Cadherin Superfamily: A Review.

Keeling J, Falchook G J Immunother Precis Oncol. 2025; 8(1):23-33.

PMID: 39811419 PMC: 11728384. DOI: 10.36401/JIPO-24-20.

A trial of radiolabeled antibody yttrium-90-FF-21101 for the treatment of advanced ovarian and other cancers.

Mahalingam D, Owonikoko T, Delpassand E, Mulcahy M, Kalyan A, Ulahannan S Cancer. 2025; 131(1):e35680.

PMID: 39748726 PMC: 11696210. DOI: 10.1002/cncr.35680.

Logic-gated and contextual control of immunotherapy for solid tumors: contrasting multi-specific T cell engagers and CAR-T cell therapies.

Nolan-Stevaux O, Smith R Front Immunol. 2024; 15:1490911.

PMID: 39606234 PMC: 11599190. DOI: 10.3389/fimmu.2024.1490911.

Update on current and new potential immunotherapies in breast cancer, from bench to bedside.

Alaluf E, Shalamov M, Sonnenblick A Front Immunol. 2024; 15:1287824.

PMID: 38433837 PMC: 10905744. DOI: 10.3389/fimmu.2024.1287824.

Revolutionizing cancer immunotherapy: unleashing the potential of bispecific antibodies for targeted treatment.

Guo X, Wu Y, Xue Y, Xie N, Shen G Front Immunol. 2023; 14:1291836.

PMID: 38106416 PMC: 10722299. DOI: 10.3389/fimmu.2023.1291836.

References

Runcie K, Budman D, John V, Seetharamu N . Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics. Mol Med. 2018; 24(1):50. PMC: 6154901. DOI: 10.1186/s10020-018-0051-4. View

Topp M, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S . Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014; 32(36):4134-40. DOI: 10.1200/JCO.2014.56.3247. View

Berx G, van Roy F . Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol. 2010; 1(6):a003129. PMC: 2882122. DOI: 10.1101/cshperspect.a003129. View

Kebenko M, Goebeler M, Wolf M, Hasenburg A, Seggewiss-Bernhardt R, Ritter B . A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors. Oncoimmunology. 2018; 7(8):e1450710. PMC: 6136859. DOI: 10.1080/2162402X.2018.1450710. View

Vieira A, Paredes J . P-cadherin and the journey to cancer metastasis. Mol Cancer. 2015; 14:178. PMC: 4595126. DOI: 10.1186/s12943-015-0448-4. View

Park J, Park E, Han S, Im S, Kim T, Kim W . Down-regulation of P-cadherin with PF-03732010 inhibits cell migration and tumor growth in gastric cancer. Invest New Drugs. 2011; 30(4):1404-12. DOI: 10.1007/s10637-011-9710-9. View

Hummel H, Kufer P, Grullich C, Seggewiss-Bernhardt R, Deschler-Baier B, Chatterjee M . Pasotuxizumab, a BiTE immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings. Immunotherapy. 2020; 13(2):125-141. DOI: 10.2217/imt-2020-0256. View

VAN Roy F, Berx G . The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008; 65(23):3756-88. PMC: 11131785. DOI: 10.1007/s00018-008-8281-1. View

Root A, Cao W, Li B, LaPan P, Meade C, Sanford J . Development of PF-06671008, a Highly Potent Anti-P-cadherin/Anti-CD3 Bispecific DART Molecule with Extended Half-Life for the Treatment of Cancer. Antibodies (Basel). 2019; 5(1). PMC: 6698862. DOI: 10.3390/antib5010006. View

10.

Velasquez M, Bonifant C, Gottschalk S . Redirecting T cells to hematological malignancies with bispecific antibodies. Blood. 2017; 131(1):30-38. PMC: 5755042. DOI: 10.1182/blood-2017-06-741058. View

11.

Moore P, Zhang W, Rainey G, Burke S, Li H, Huang L . Application of dual affinity retargeting molecules to achieve optimal redirected T-cell killing of B-cell lymphoma. Blood. 2011; 117(17):4542-51. DOI: 10.1182/blood-2010-09-306449. View

12.

Van Marck V, Stove C, Jacobs K, Van den Eynden G, Bracke M . P-cadherin in adhesion and invasion: opposite roles in colon and bladder carcinoma. Int J Cancer. 2010; 128(5):1031-44. DOI: 10.1002/ijc.25427. View

13.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

14.

Saber H, Del Valle P, Ricks T, Leighton J . An FDA oncology analysis of CD3 bispecific constructs and first-in-human dose selection. Regul Toxicol Pharmacol. 2017; 90:144-152. DOI: 10.1016/j.yrtph.2017.09.001. View

15.

Kantarjian H, Stein A, Gokbuget N, Fielding A, Schuh A, Ribera J . Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017; 376(9):836-847. PMC: 5881572. DOI: 10.1056/NEJMoa1609783. View

16.

Subbiah V, Erwin W, Mawlawi O, McCoy A, Wages D, Wheeler C . Phase I Study of P-cadherin-targeted Radioimmunotherapy with Y-FF-21101 Monoclonal Antibody in Solid Tumors. Clin Cancer Res. 2020; 26(22):5830-5842. DOI: 10.1158/1078-0432.CCR-20-0037. View

17.

Kamperschroer C, Shenton J, Lebrec H, Leighton J, Moore P, Thomas O . Summary of a workshop on preclinical and translational safety assessment of CD3 bispecifics. J Immunotoxicol. 2020; 17(1):67-85. DOI: 10.1080/1547691X.2020.1729902. View

18.

van Roy F . Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer. 2014; 14(2):121-34. DOI: 10.1038/nrc3647. View

19.

Yu S, Li A, Liu Q, Yuan X, Xu H, Jiao D . Recent advances of bispecific antibodies in solid tumors. J Hematol Oncol. 2017; 10(1):155. PMC: 5607507. DOI: 10.1186/s13045-017-0522-z. View

20.

Fisher T, Hooper A, Lucas J, Clark T, Rohner A, Peano B . A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established solid tumors in mice. Cancer Immunol Immunother. 2017; 67(2):247-259. PMC: 11028296. DOI: 10.1007/s00262-017-2081-0. View