{"doi":"10.1002/cam4.6877","title":"Phase I study of sapanisertib (CB‐228/TAK‐228/MLN0128) in combination with ziv‐aflibercept in patients with advanced solid tumors","abstract":"BACKGROUND: Sapanisertib is a potent ATP-competitive, dual inhibitor of mTORC1/2. Ziv-aflibercept is a recombinant fusion protein comprising human VEGF receptor extracellular domains fused to human immunoglobulin G1. HIF-1α inhibition in combination with anti-angiogenic therapy is a promising anti-tumor strategy. This Phase 1 dose-escalation/expansion study assessed safety/ tolerability of sapanisertib in combination with ziv-aflibercept in advanced solid tumors. METHODS: Fifty-five patients with heavily pre-treated advanced metastatic solid tumors resistant or refractory to standard treatment received treatment on a range of dose levels. RESULTS: Fifty-five patients were enrolled and treated across a range of dose levels. Forty were female (73%), median age was 62 (range: 21-79), and ECOG PS was 0 (9, 16%) or 1 (46, 84%). Most common tumor types included ovarian (8), colorectal (8), sarcoma (8), breast (3), cervical (4), and endometrial (4). Median number of prior lines of therapy was 4 (range 2-11). Sapanisertib 4 mg orally 3 days on and 4 days off plus 3 mg/kg ziv-aflibercept IV every 2 weeks on a 28-day cycle was defined as the maximum tolerated dose. Most frequent treatment-related grade ≥2 adverse events included hypertension, fatigue, anorexia, hypertriglyceridemia, diarrhea, nausea, mucositis, and serum lipase increase. There were no grade 5 events. In patients with evaluable disease (n = 50), 37 patients (74%) achieved stable disease (SD) as best response, two patients (4%) achieved a confirmed partial response (PR); disease control rate (DCR) (CR + SD + PR) was 78%. CONCLUSION: The combination of sapanisertib and ziv-aflibercept was generally tolerable and demonstrated anti-tumor activity in heavily pre-treated patients with advanced malignancies.","journal":"Cancer Medicine","year":2024,"id":453376,"datarank":0.41812151312886026,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.08853782652842729,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.08853782652842729,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":7,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02159989resesese"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":266106,"name":"Bettzy Stephen","orcid":"0000-0003-1653-2012","position":1,"is_corresponding":false},{"id":241553,"name":"Siqing Fu","orcid":"0000-0002-1933-0419","position":2,"is_corresponding":false},{"id":266107,"name":"Daniel D. Karp","orcid":"0000-0002-5017-328X","position":3,"is_corresponding":false},{"id":226642,"name":"Vivek Subbiah","orcid":"0000-0002-6064-6837","position":4,"is_corresponding":false},{"id":269051,"name":"Jordi Rodon Ahnert","orcid":null,"position":5,"is_corresponding":false},{"id":258839,"name":"Sarina A. Piha‐Paul","orcid":"0000-0001-9455-1660","position":6,"is_corresponding":false},{"id":237210,"name":"John Wright","orcid":"0000-0001-9572-7293","position":7,"is_corresponding":false},{"id":1276303,"name":"Senait N. Fessahaye","orcid":null,"position":8,"is_corresponding":false},{"id":427290,"name":"Fengying Ouyang","orcid":null,"position":9,"is_corresponding":false},{"id":666212,"name":"Bülent Yılmaz","orcid":"0000-0002-9458-2253","position":10,"is_corresponding":false},{"id":70220,"name":"Funda Meric‐Bernstam","orcid":"0000-0001-6816-6072","position":11,"is_corresponding":false},{"id":266105,"name":"Aung Naing","orcid":"0000-0002-4803-8513","position":12,"is_corresponding":false},{"id":660100,"name":"Niamh Coleman","orcid":"0000-0002-5803-9528","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:02:58.784290Z","pmid":"38400671","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":[]}