{"doi":"10.1136/jitc-2021-002446","title":"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","abstract":"BACKGROUND: 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.","journal":"Journal for ImmunoTherapy of Cancer","year":2021,"id":171817,"datarank":1.0178957824360766,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.5235202525354271,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.5235202525354271,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":24,"citers_with_citation_signal":21,"citers_with_endowment":21,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03013491"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":282233,"name":"Omid Hamid","orcid":"0000-0002-8238-4655","position":1,"is_corresponding":false},{"id":706773,"name":"Elisabeth G.E. de Vries","orcid":"0000-0002-8949-7425","position":2,"is_corresponding":false},{"id":25300,"name":"Patrick A. Ott","orcid":"0000-0002-4253-943X","position":3,"is_corresponding":false},{"id":707214,"name":"Javier García-Corbacho","orcid":null,"position":4,"is_corresponding":false},{"id":706774,"name":"Valentina Boni","orcid":"0000-0002-8675-0018","position":5,"is_corresponding":false},{"id":567086,"name":"Johanna C. Bendell","orcid":"0000-0001-9426-5891","position":6,"is_corresponding":false},{"id":311732,"name":"Karen A. Autio","orcid":"0000-0003-0720-0390","position":7,"is_corresponding":false},{"id":706775,"name":"Daniel C. Cho","orcid":"0000-0002-4248-6382","position":8,"is_corresponding":false},{"id":639045,"name":"Ruth Plummer","orcid":"0000-0003-0107-1444","position":9,"is_corresponding":false},{"id":707215,"name":"Mark Stroh","orcid":null,"position":10,"is_corresponding":false},{"id":707216,"name":"Lawrence Lu","orcid":null,"position":11,"is_corresponding":false},{"id":706776,"name":"Fiona Thistlethwaite","orcid":"0000-0002-4832-7008","position":12,"is_corresponding":false},{"id":595044,"name":"Rachel E. Sanborn","orcid":"0000-0003-0542-6054","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T23:46:33.067299Z","pmid":"34301808","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}