Aliqopa (copanlisib) / Bayer - LARVOL DELTA

Durvalumab and Copanlisib Combination in Unresectable Stage III NSCLC Consolidation with Exceptional PFS (ESMO 2025) - No abstract available

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Copanlisib With Ibrutinib for Patients With Recurrent/ Refractory Primary Central Nervous System Lymphoma (PCNSL) (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma

Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma: A Phase 2 Study (SOHO 2025) - "Nearly all patients with untreated FL have tumors responsive to PI3K inhibition with copanlisib. Copanlisib with rituximab for 6 cycles has a low rate of autoimmune toxicities and achieves durable remissions."

P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

NCI-2018-01880: Copanlisib and Nivolumab in Treating Patients With Richter's Transformation or Transformed Indolent Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jul 2025 ➔ Nov 2025 | Trial primary completion date: Jul 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Waldenstrom Macroglobulinemia • PD-L1

LCD: Lung Cancer With Copanlisib and Durvalumab (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Zhonglin Hao | Trial completion date: Jun 2025 ➔ Nov 2025 | Trial primary completion date: Jun 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

THE BTK DEGRADER BGB-16673 AND THE BCL2 INHIBITOR SONROTOCLAX SHOWS ANTI-TUMOR ACTIVITY AS SINGLE AGENTS AND IN COMBINATION IN MARGINAL ZONE LYMPHOMA MODELS (ICML 2025) - "The activity did not differ from the BTK inhibitor zanubrutinib and, accordingly, was limited in cells resistant to ibrutinib (n. = 2), idelalisib (n...= 1), and copanlisib/venetoclax (n...Karpas1718, SSK41, VL51 and HC1 were exposed to BGB-16673 plus lenalidomide, selinexor, venetoclax, sonrotoclax (BGB-11417), bendamustine, tazemetostat and rituximab... Its ability to degrade BTK protein, combined with its synergistic effects with other targeted therapies, positions BGB-16673 as a promising candidate for further development in MZL patients. The 2nd generation BCL2 inhibitor sonrotoclax appears as another drug to be explored in the same patient populations, possibly combining the two molecules."

B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • BCL2L1 • CRBN • MCL1

Lessons learned from experience of phosphatidylinositol 3-kinase inhibitors in chronic lymphocytic leukemia and lymphoma. (PubMed, Haematologica) - "The recently published CHRONOS-4 clinical trial4, a randomized placebocontrolled study comparing copanlisib in combination with bendamustine plus rituximab and placebo with bendamustine plus rituximab, demonstrated that adding copanlisib to the standard-of-care bendamustine plus rituximab did not improve survival and increased toxicity. In this article, we examine the scientific rationale, clinical experience, regulatory hurdles, and future developments of PI3K inhibitors. We analyze the complexity of balancing PI3K therapeutic potential and safety."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

BCL-2 family inhibition enhances MTORC1/2 inhibition in PIK3CA mutant colorectal cancer. (PubMed, Mol Cancer Ther) - "Across multiple in vitro and in vivo CRC models, navitoclax enhanced PI3K/MTOR inhibition (copanlisib, sapanisertib, and dactolisib) and induced apoptosis. Furthermore, we identify BCL-xL as the major BCL-2 family target important for the response to this combination in this setting. This provides a strong rationale for MTORC1/2 and BCL-2 family inhibition as a potential treatment strategy for PIK3CA mutant CRCs."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • BCL2 • BCL2L1 • KRAS • PIK3CA

Copanlisib Plus Venetoclax in R/R DLBCL (clinicaltrials.gov) - P1/2 | N=48 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Jun 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Oct 2026 ➔ Aug 2025

Trial completion date • Breast Cancer • Endometrial Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • PGR • PI3K • PIK3CA • PIK3R1 • PTEN

Safety and efficacyof the combination of copanlisib and nivolumab in patients with Richter's transformation or transformed non-Hodgkin lymphoma: results from a phase I trial. (PubMed, Haematologica) - "Responding RT patients exhibited sustained activation of IFN-α and IFN-γ signaling pathways in CD4+ and CD8+ T cells. Overall, treatment with copanlisib and nivolumab demonstrated manageable toxicity and promising clinical efficacy in tNHL patients."

Journal • P1 data • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • CD4 • CD8 • IFNA1 • IFNG • MYC

COMBINATION OF THE INTRAVENOUS PI3K INHIBITOR COPANLISIB IN COMBINATION WITH OBINUTUZUMAB IN PATIENTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA AND HIGH TUMOR BURDEN (ICML 2025) - "Copanlisib plus Obinutuzumab did not achieve the prespecified PFS improvement but demonstrated durable responses and manageable toxicity, suggesting potential benefit for selected patients."

Clinical • Combination therapy • IO biomarker • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Oncology • BCL2

A PROSPECTIVE MULTICENTER PHASE 2 STUDY OF THE CHEMOTHERAPY-FREE COMBINATION OF THE INTRAVENOUS PHOSPHATIDYLINOSITOL-3-KINASE (PI3K) INHIBITOR COPANLISIB IN COMBINATION WITH OBINUTUZUMAB IN PATIENTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA (FL) AND A HIGH TUMOR BURDEN (ALTERNATIVE-C) (EHA 2025) - "Copanlisib plus obinutuzumab did not achieve the prespecified PFS improvement but demonstrated durable responses and manageable toxicity, suggesting potential benefit for selected patients."

Clinical • Combination therapy • IO biomarker • P2 data • Cardiovascular • Diabetes • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertension • Indolent Lymphoma • Infectious Disease • Lymphoma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • BCL2

Copanlisib in combination with rituximab and bendamustine for transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma patients: Results from the phase II multicentre FIL Copa-BR trial from Fondazione Italiana Linfomi (FIL). (PubMed, Br J Haematol) - "Due to limited efficacy, poor tolerability and emerging alternative treatments, the trial was terminated prematurely. Copa-BR showed limited activity and an unfavourable safety profile, discouraging further investigation of this combination in ASCT- and CAR-T-ineligible R/R DLBCL."

Journal • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Thrombocytopenia • Transplantation

Copanlisib and Avelumab as a Maintenance Therapy for Advanced Bladder Cancer (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: VA Office of Research and Development | N=29 ➔ 0 | Trial completion date: Jun 2029 ➔ Jun 2025 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Dec 2028 ➔ Jun 2025

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Digital spatial profiling of advanced solid tumors and lymphomas from a phase 1 trial of copanlisib and nivolumab. (ASCO 2025) - P1 | "As part of the exploratory objectives in the Phase 1B trial (NCT03502733) evaluating adult patients(pts) with solid tumors and lymphomas copanisib (C), nivolumab (N) + ipilumumab (I), we employed the NanoString-Bruker GeoMx DSP platform to evaluate spatial heterogeneity in differentially regulated biomarkers... GeoMx DSP demonstrated its capability to investigate phospho-signaling and immune profiles in tumor and stromal compartments of small biopsies, highlighting its potential to enhance the understanding of TMEs in clinical studies. Further applications may provide critical insights for clinical cancer trials."

IO biomarker • Metastases • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • CD20 • CD8 • CD80 • CTLA4 • FOXP3 • PD-1 • PD-L1 • PIK3IP1 • PTPRC

Industry promotion of oncology drugs with accelerated approval that failed confirmatory trials. (ASCO 2025) - "Pepaxto was excluded from our analysis as it had no reported payments on OpenPayments...Following announcement of negative postapproval confirmatory study results, average monthly payments received by all physicians increased for Marqibo (vinCRIStine sulfate) from $138 in the year preceding announcement to $164 during the period between announcement of negative results and market withdrawal, but decreased for Farydak (panobinostat) ($12,317 to $4,916), Blenrep (belantamab mafodotin) ($152,417 to $119,394), and Ukoniq (umbralisib) ($23,139 to $14,130). Lartruvo (olaratumab) and Aliqopa (copanlisib) had almost no payments after announcement of negative confirmatory study results. Industry payments for oncology drugs with accelerated approvals mostly decreased after announcement of negative confirmatory trial results; however, there was evidence of continued promotion for certain drugs until a request for voluntary withdrawal was made by FDA. This suggests that regulatory..."

Oncology

Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer (clinicaltrials.gov) - P1 | N=17 | Terminated | Sponsor: Mayo Clinic | N=39 ➔ 17 | Suspended ➔ Terminated; funding - sponsor filing Chapter 11 bankruptcy

Enrollment change • Trial termination • Breast Cancer • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Marginal Zone Lymphoma • Mycosis Fungoides • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma

Combinatorial screen with standard of care and selected anticancer agents identifies multiple combinations with activity against a panel of patient-derived colorectal organoids (AACR 2025) - "Following compound addition, organoid growth was measured by live bright field imaging every 24 h and cell viability was determined by CellTiter-Glo 3D at 48 h and 168 h. Modest responses were observed in most models from the combination of leucovorin with 5-FU; however, >1 log of cytotoxicity was observed in only several models. The panel was more responsive to FOLFOX, which was consistent with the sensitivity of models to oxaliplatin. Responses to TAS-102 varied and >1 log of cytotoxicity was observed in several models...Combination of the BCL-2/BCL-xL inhibitor pelcitoclax plus cobimetinib achieved >1 log of cytotoxicity in most organoid models. Combinations of cobimetinib with the EGFR inhibitors erlotinib, afatinib or cetuximab demonstrated synergy in many organoids according to the Bliss independence model and frequently achieved ≥1 log of cytotoxicity...The combination of cobimetinib and MRTX1133 had synergistic activity by Bliss independence in multiple..."

Clinical • Oncology • BCL2 • BCL2L1 • BRAF • KRAS • PIK3CA

Development of anti-CD21 Chimeric Antigen Receptor (CAR)-T Cells for T-Cell Acute Lymphoblastic Leukemia (T-ALL) - CAR engineering for a complex antigen. (ASGCT 2025) - "The dual αδ PI3K inhibitor copanlisib upregulated CD21 in T-ALL cell lines and PDX both in vitro and in vivo. Anti-CD21 Fab-CAR-T cells, targeting membrane-proximal epitopes, showed potent anti-CD21 activity. Pharmacological upregulation of CD21 can enhance efficacy in low antigen density. This novel approach avoids fratricide and T-cell aplasia, offering promise for treating T-ALL Disease Focus of Abstract:Leukemia"

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD21 • CD7

Testing the Addition of Copanlisib to Eribulin in Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Completed ➔ Active, not recruiting | Trial completion date: Mar 2024 ➔ May 2026

Enrollment closed • Trial completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • PGR • PIK3CA • PTEN

Phosphatidylinositol 3-Kinase Inhibition and Allogeneic Stem Cell Transplantation Can Overcome Chemotherapy Resistance in Refractory Burkitt Lymphoma. (PubMed, J Hematol) - "Our report demonstrates that targeting B-cell receptor signaling via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway with copanlisib can overcome chemotherapy resistance and achieve complete remission in relapsed Burkitt lymphoma. This novel approach, followed by consolidation with allogeneic hematopoietic stem cell transplantation can provide durable complete remission by harnessing the immune graft-versus-lymphoma effect in chemoresistant Burkitt lymphoma."

Journal • Bone Marrow Transplantation • Burkitt Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Transplantation

Co-alterations in PIK3CA and ARID1A lead to greater sensitivity to PI3K pathway inhibition (AACR 2025) - "Previously we have shown that patients with mutations in both genes are more sensitive to copanlisib (cop) treatment than those with just PIK3CA(PK) mutation...An enhanced response was observed with some other PI3K inhibitors, including sapanisertib (PK=0.13; PKAD=0.014; p < 0.005) everolimus (PK=0.66, PKAD=0.36; p < 0.005) and capivasertib (PK=0.85; PKAD=0.47; p < 0.05). Cancers with PK and AD alterations have enhanced efficacy to PI3K pathway inhibition, especially those inhibitors with downstream activity against AKT or MTOR. Further mechanistic and in vivo studies are warranted in addition to further clinical validation."

Colorectal Cancer • Endometrial Cancer • Oncology • Solid Tumor • ARID1A • IFNG • IL6 • PIK3CA

Copanlisib and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=8 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Mar 2025 ➔ Feb 2026 | Trial primary completion date: Mar 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • BCL2 • CCND1 • CD20 • CD5 • PAX5

Retraction Note: Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer. (PubMed, Cell Death Dis) - No abstract available

Journal • Colorectal Cancer • Oncology • Solid Tumor • FOXO3