Citations 3
535 EVEREST-2: a phase 1/2 study of A2B694, a logic-gated Tmod CAR T therapy to treat solid tumors expressing mesothelin (MSLN) with HLA-A*02 loss of heterozygosity: initial safety and efficacy results
Hecht, J. Randolph, Spencer, Kristen , Marar, Rosalyn, Avila, Monica , Patel, Sandip Pravin , Maloney, David G. , Ulrickson, Matthew L. , Neal, Joel M, He, Kai , Go, William Y., Mitchell, Jasmine , Lou, Yanyan, Kundranda, Madappa N. , Mardiros, Armen, Bretzlaff, William, Xuan, Jacqueline D, Welch, John S. , Molina, Julian R. , Ward, Jeffrey P. , Kirtane, Kedar , Garon, Edward B. , Creelan, Ben , Maus, Marcela V , Eng, Cathy , Hazim, Antonious , Warner, Allison Betof , Neal, Joel M, Dorigo, Oliver , Vu, Peter , Xuan, Jacqueline D, Wise, Andrea, Ng, Eric W, Punekar, Salman R.
Regular and Young Investigator Award Abstracts | November 10, 2025 | Volume: No volume available | Issue: No issue available | Pages: A611-A612
627 EVEREST-2: a seamless phase 1/2 study of A2B694, a logic-gated Tmod CAR T-cell therapy, in patients with mesothelin-expressing solid tumors with human leukocyte antigen-A*02 loss of heterozygosity
Molina, Julian R. , Avila, Monica , Konecny, Gottfried E. , Block, Matthew S. , Lou, Yanyan, Xuan, Jacqueline D, Eskander, Ramez N. , Ong, Gayanie, Langeberg, Wendy J., Mardiros, Armen, Maloney, David G. , Welch, John S. , Hecht, J. Randolph , Hazim, Antonious , Dorigo, Oliver , Punekar, Salman R. , Simeone, Diane M. , Kirtane, Kedar , Ward, Jeffrey P. , Specht, Jennifer M. , Boyd, Leslie R. , Park, Jong Chul , Xuan, Jacqueline D, Davila, Marco L , Maus, Marcela V , Locke, Frederick L. , Wise, Andrea
Regular and Young Investigator Award Abstracts | November 5, 2024 | Volume: No volume available | Issue: No issue available | Pages: A721-A722
Phase 1 first-in-human study of PF-07257876, a novel CD47/PD-L1 bispecific checkpoint inhibitor, in patients with PD-1/PD-L1-refractory and -naïve advanced solid tumors.
Carneiro, Benedito A. , Safran, Howard , Hamid, Omid , Savvides, Panos, Gutierrez, Martin , Zhao, Yujie , Abbruzzese, James L. , Weroha, Saravut J., Harris, Loleta D., Kent, Sean , Pierceall, William E., Skoura, Athanasia, Zheng, Jenny, Kern, Kenneth A. , Santana-Dávila, Rafael , Beck, J. Thaddeus , Spira, Alexander I. , Savvides, Panos, Ward, Jeffrey P. , Thomas, Jacob Stephen
Journal of Clinical Oncology | June 4, 2023 | Volume: 41 | Issue: 16_suppl | Pages: 2529-2529
10.1200/jco.2023.41.16_suppl.2529
2529 Background: Tumor expression of the antiphagocytic protein CD47 (integrin associated protein) may lead to immunotherapy resistance (IO-R). PF-07257876 is a novel, IgG1, Fc-active, bispecific antibody targeting CD47 and PD-L1 designed to reverse IO-R, decrease anemia risk, and eliminate a priming dose. We report a Phase 1 dose escalation study (NCT04881045) in patients (pts) with advanced solid tumors, both IO-refractory and IO-naïve. Methods: The study enrolled pts ≥18 yrs with advanced non–small-cell lung carcinoma (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN) with PD-L1 expression >1% post anti-PD-1/PD-L1 therapy. Pts with other PD-L1+ tumors known to express CD47 were included (prior IO not required). Pts received PF-07257876 at escalating dose levels in 28-day cycles. Primary objectives were safety (dose-limiting toxicity [DLT] rate), tolerability, and determination of Recommended Phase 2 Dose (RP2D). Secondary and exploratory objectives included pharmacokinetics (PK), blood receptor occupancy (RO), CD47 levels by immunohistochemistry (IHC), tissue biopsy findings, and objective response rate (ORR) per RECIST v.1.1. Results: As of 20OCT2022, 18 pts were enrolled (NSCLC: n = 6; SCCHN: n = 4; other: n = 8). Median (range) age 68 (46–79) yrs. PF-07257876 was given at ascending doses, 150-2400 mg by subcutaneous (SC) injection or SC infusion every 2 weeks. 16 (89%) pts had treatment-related adverse events (TRAEs): Grades 1/2: n = 12 (67%); Grade 3: n = 1 (6%); Grade 4: n = 3 (17%); no Grade 5. Most common TRAEs: injection site reaction/erythema (n = 13, 72%), thrombocytopenia (n = 6, 33%), anemia (n = 5, 28%), and nausea (n = 4, 22%). DLTs occurred in 2 of 3 pts at the highest tested dose (Grade 4 neutropenia and thrombocytopenia, n = 1; Grade 4 thrombocytopenia, n = 1; both pts recovered). One pt with IO-R SCCHN had a confirmed partial response (duration of response 16 wks). ORR was 5.6% (1/18). Drug exposure increase after 1st dose was not dose proportional. Blood RO was > 95% for PD-L1 and > 70% for CD47 with drug exposure. All pts’ baseline CD47 IHC levels were moderate to high. Pharmacodynamics cytokine profiling showed notable dose-response increases of IFNg, TNFa, CXCL9/10, CCL3/4, without IL-6 increase. Conclusions: PF-07257876 was well tolerated with manageable toxicity. Incidence and grade of anemia or thrombocytopenia were manageable. Target engagement of CD47 and PD-L1 in peripheral blood was high. Innate and adaptive cytokine modulation was observed. Antitumor activity was modest. Expansion is ongoing at 1800 mg. Clinical trial information: NCT04881045 .