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dc.contributor.authorSanborn, R. E.
dc.contributor.authorHamid, O.
dc.contributor.authorde Vries, E. G.
dc.contributor.authorOtt, P. A.
dc.contributor.authorGarcia-Corbacho, J.
dc.contributor.authorBoni, V.
dc.contributor.authorBendell, J.
dc.contributor.authorAutio, K. A.
dc.contributor.authorCho, D. C.
dc.contributor.authorPlummer, R.
dc.contributor.authorStroh, M.
dc.contributor.authorLu, L
dc.contributor.authorThistlethwaite, Fiona C
dc.date.accessioned2021-08-17T12:22:46Z
dc.date.available2021-08-17T12:22:46Z
dc.date.issued2021en
dc.identifier.citationSanborn RE, Hamid O, de Vries EG, Ott PA, Garcia-Corbacho J, Boni V, et al. CX-072 (pacmilimab), a Probody PD-L1 inhibitor, in combination with ipilimumab in patients with advanced solid tumors (PROCLAIM-CX-072): a first-in-human, dose-finding study. J Immunother Cancer. 2021 Jul;9(7):e002446.en
dc.identifier.pmid34301808en
dc.identifier.doi10.1136/jitc-2021-002446en
dc.identifier.urihttp://hdl.handle.net/10541/624455
dc.description.abstractBackground: Probody® therapeutics are antibody prodrugs designed to be activated by tumor-associated proteases. This conditional activation restricts antibody binding to the tumor microenvironment, thereby minimizing 'off-tumor' toxicity. Here, we report the phase 1 data from the first-in-human study of CX-072 (pacmilimab), a Probody immune checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1), in combination with the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab. Methods: Adults (n=27) with advanced solid tumors (naive to PD-L1/programmed cell death protein 1 or CTLA-4 inhibitors) were enrolled in the phase 1 combination therapy dose-escalation portion of this multicenter, open-label, phase 1/2 study (NCT03013491). Dose-escalation pacmilimab/ipilimumab followed a standard 3+3 design and continued until the maximum tolerated dose (MTD) was determined. Pacmilimab+ipilimumab was administered intravenously every 3 weeks for four cycles, followed by pacmilimab administered every 2 weeks as monotherapy. The primary objective was identification of dose-limiting toxicities and determination of the MTD. Other endpoints included the rate of objective response (Response Evaluation Criteria In Solid Tumors v.1.1). Results: Twenty-seven patients were enrolled in pacmilimab (mg/kg)+ipilimumab (mg/kg) dose-escalation cohorts: 0.3+3 (n=6); 1+3 (n=3); 3+3 (n=3); 10+3 (n=8); 10+6 (n=6); and 10+10 (n=1). Dose-limiting toxicities occurred in three patients, one at the 0.3+3 dose level (grade 3 dyspnea/pneumonitis) and two at the 10+6 dose level (grade 3 colitis, grade 3 increased aspartate aminotransferase). The MTD and recommended phase 2 dose was pacmilimab 10 mg/kg+ipilimumab 3 mg/kg administered every 3 weeks. Pacmilimab-related grade 3-4 adverse events (AEs) and grade 3-4 immune-related AEs were reported in nine (33%) and six (22%) patients, respectively. Three patients (11%) discontinued treatment because of AEs. The overall response rate was 19% (95% CI 6.3 to 38.1), with one complete (anal squamous cell carcinoma) and four partial responses (cancer of unknown primary, leiomyosarcoma, mesothelioma, testicular cancer). Responses lasted for >12 months in four patients. Conclusions: The MTD and recommended phase 2 dose of pacmilimab (10 mg/kg)+ipilimumab (3 mg/kg) every 3 weeks is active and has a favorable tolerability profile.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1136/jitc-2021-002446en
dc.titleCX-072 (pacmilimab), a Probody PD-L1 inhibitor, in combination with ipilimumab in patients with advanced solid tumors (PROCLAIM-CX-072): a first-in-human, dose-finding studyen
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USAen
dc.identifier.journalJournal for Immunotherapy of Canceren
dc.description.noteen]
refterms.dateFOA2021-08-18T09:58:14Z


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