{"doi":"10.1002/hon.70094_232","title":"232 | COMBINATION OF THE INTRAVENOUS PI3K INHIBITOR COPANLISIB IN COMBINATION WITH OBINUTUZUMAB IN PATIENTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA AND HIGH TUMOR BURDEN","abstract":"Background: Immunochemotherapy has demonstrated long-term efficacy in follicular lymphoma but is associated with significant toxicity. The PI3K inhibitor copanlisib has shown promising response rates in relapsed indolent lymphoma. Methods: This prospective, multicenter, single-arm phase 2 trial evaluated the efficacy and safety of a chemotherapy-free regimen of copanlisib plus obinutuzumab in adult patients with previously untreated advanced-stage follicular lymphoma. Patients received six 28-day induction cycles of copanlisib and obinutuzumab, followed by consolidation and maintenance in responders for a total duration of 120 weeks. The primary endpoint was one-year progression-free survival (PFS) status. The trial was powered to detect a 10% improvement over 85% one-year PFS (expected with chemotherapy only) in a one-sided binomial test with 5% significance level. Secondary endpoints included overall response rate (ORR), failure-free survival (FFS), duration of response (DoR), continuous PFS, overall survival (OS) and minimal residual disease (MRD). Results: Among 102 enrolled patients, 93 were evaluable at one year: 76 (82%) achieved a remission including 17 (18%) complete response (CR). 2 (2%) had stable disease, 11 (12%) disease progression, and 4 (4%) died within one year. The one-year PFS was 84%, not meeting the prespecified improvement over the expected PFS of 85% (p = 0.68). After a median follow-up of 2.4 years, FFS was 84% [95% CI: 77, 92] at one year and 70% [95% CI: 61, 80] at two years. DoR from end of induction was 87% [95% CI: 80, 94] at one year and 71% [95% CI: 61, 83] at two years. Two-year PFS probability was 75% [95% CI: 67, 84]. One- and two-year OS probabilities were 97% [95% CI: 93, 100] and 92% [95% CI: 87, 98]. A molecular marker for MRD was identified in 68 of 101 patients at baseline, most commonly Bcl-2/IgH-rearrangement (76%). Among 60 evaluable patients at the end of induction, 73% achieved a molecular remission. MRD positivity was more common in bone marrow (39% of 29) than peripheral blood (20% of 60). At one year from registration, 16% of 44 evaluable patients were MRD-positive. The probability of MRD-positivity at one year was much higher in patients MRD+ than MRD- at end of induction-(p < 0.0001). The most frequent grade 3/4 AEs included hypertension (198 AEs, 29 patients), hyperglycemia (47 AEs, 20 patients), neutropenia (24 AEs, 17 patients), pneumonia (18 AEs, 14 patients), and COVID-19 (5 AEs, 4 patients). Five fatal events included two COVID-19 cases, bacterial sepsis, suicide and Pneumocystis jirovecii pneumonia. Conclusion: Copanlisib plus Obinutuzumab did not achieve the prespecified PFS improvement but demonstrated durable responses and manageable toxicity, suggesting potential benefit for selected patients. Research funding declaration: The study is financially funded by Bayer HealthCare Pharmaceuticals Inc and Roche Pharma AG, Encore Abstract: EHA 2025 Keywords: non-Hodgkin; molecular targeted therapies; combination therapies Potential sources of conflict of interest: M. Hänel Consultant or advisory role: Kite/Gilead, Janssen, Sobi, Amgen, Roche, Takeda, Sanofi-Aventis, GSK, Incyte, Pfizer, BMS Honoraria: Kite/Gilead, Sobi, BMS, Novartis C. Pott Consultant or advisory role: Roche Honoraria: Roche M. Dreyling Consultant or advisory role: Abbvie, AstraZeneca, AvenCell, Beigene, BMS, Genmab, Gilead/Kite, Incyte, Janssen, Lilly/Loxo, Novartis, Roche, Sobi Honoraria: AstraZeneca, Beigene, BMS, Gilead/Kite, Janssen, Lilly, Roche","journal":"Hematological Oncology","year":2025,"id":568546,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1037563,"name":"Vindi Jurinović","orcid":null,"position":1,"is_corresponding":false},{"id":1472821,"name":"Ulf Schnetzke","orcid":"0000-0001-7455-8988","position":2,"is_corresponding":false},{"id":1472822,"name":"Mathias Hänel","orcid":"0000-0002-4767-3275","position":3,"is_corresponding":false},{"id":1472773,"name":"Christiane Pott","orcid":"0009-0005-9260-8340","position":4,"is_corresponding":false},{"id":1021006,"name":"Enrico Schalk","orcid":"0000-0003-1892-5098","position":5,"is_corresponding":false},{"id":1021000,"name":"Martin Schmidt‐Hieber","orcid":"0000-0002-3071-6945","position":6,"is_corresponding":false},{"id":1472823,"name":"Katharina Clemm von Hohenberg","orcid":"0000-0002-2853-208X","position":7,"is_corresponding":false},{"id":1472824,"name":"Eva Hoster","orcid":"0000-0002-0749-1389","position":8,"is_corresponding":false},{"id":1200345,"name":"Tobias Tix","orcid":null,"position":9,"is_corresponding":false},{"id":1473400,"name":"Sabine Witt","orcid":null,"position":10,"is_corresponding":false},{"id":1473401,"name":"M. Dreyling","orcid":null,"position":11,"is_corresponding":false},{"id":1473399,"name":"C Schmidt","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:56:52.212268Z","pmid":null,"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":[]}