Aliqopa (copanlisib) / Bayer - LARVOL DELTA

Characterization of pityriasis rubra pilaris with hematological malignancies: Paraneoplastic disease and targeted therapy reactions (ASH 2025) - "The ALL patient was related to ponatinib, the non-Hodgkin's lymphoma case was related to copanlisib, 2 CLL patients were related to duvelisib, and 2 CLL were related to idealisib...With regards to paraneoplastic treatment, topical treatment included corticosteroids, emollients, topical urea, retinoids, and fluorouracil. Systemic treatments included methotrexate, systemic corticosteroids, and phototherapy...Specialists should maintain a high index of suspicion for PRP as a paraneoplastic signal or drug-related adverse event. Future studies are needed to elucidate such presentations and guide management."

Chronic Lymphocytic Leukemia • Dermatology • Dermatopathology • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

Discovery of drug combinations with momelotinib to improve myelofibrosis outcomes (ASH 2025) - "The VAF screen identified numerous inhibitors of signaling pathways operating parallel to the JAK-STAT signaling pathway including SHP2 (migoprotafib), PI3K (copanlisib), MEK (cobimetinib), agents targeting BET (BMS-986158), and STAT transcriptional targets, including BCLxL (navitoclax). The hepcidin screen identified inhibitors that combined to further suppress expression of the HiBiT transgene including CDK4 (atirmociclib) and MDM2 (navtemadlin). Notably, selinexor, an XPO1 inhibitor, combined positively with momelotinib to both kill malignant cells and suppress hepcidin expression. These results highlight several promising drug combinations that could enhance outcomes for MF patients by effectively controlling anemia and halting disease progression. These discoveries provide the scientific justification to identify optimal combination regimens aimed at addressing the multifaceted challenges of myelofibrosis."

IO biomarker • Myelofibrosis • ACVR1 • BCL2L1 • BMP6 • CDK4 • JAK1

Representation of older adults in registrational trials associated with therapeutic approvals in follicular lymphoma (ASH 2025) - "Of the drugs approved, 2 were bispecific antibodies (BsAb,epcoritamab, mosunetuzumab), 3 were chimeric antigen receptor-T (CAR-T) products (lisocabtagene,axicabtagene, tisagenleucel), 3 were PI3K inhibitors (umbralisib, copanlisib, duvelisib), 2 were monoclonalantibodies (obinutuzumab with chemotherapy, obinutuzumab with bendamustine), and 1 each ofselective EZH2 inhibitor (tazemetostat), immunomodulator (lenalidomide with rituximab), and BTKinhibitor (zanubrutinib). Most registrational trials for FL do report a subgroup of OA, although inclusion of OAremains suboptimal at 37%. Representation and reporting of pts≥ 75 yrs is significantly low at only 8%,despite this group representing 20% pts at diagnosis. Reporting of trials should include and distinguishpts ≥65 yrs and ≥75 yrs for subgroup analyses."

Clinical • Follicular Lymphoma • Geriatric Disorders • Hematological Malignancies • Lymphoma

THE RAF/MEK INHIBITOR VS-6766 SHOWS EFFICACY IN RAS-MUTANT PEDIATRIC PRECLINICAL XENOGRAFT MODELS- A REPORT FROM THE PEDIATRIC PRECLINICAL IN VIVO TESTING CONSORTIUM (CTOS 2025) - "To evaluate drug combinations, RMS PDXs were treated with VS-6766 in doublet with 14 other drugs targeting additional areas of the MAPK/ERK pathway along with untreated control, VS-6766 alone, and vincristine + irinotecan (standard of care) for a total of 17 treatment groups...In combination testing, survival advantage was most notable when VS-6766 was combined with VS-4718 (FAK), everolimus (mTOR), copanlisib (PI3Kδ/α), capivasertib (AKT), BBP-398 (SHP2) and LY3023414 (PI3K) compared to VS-6766 alone. VS-6766 exhibited antitumor activity across several pediatric cancers... VS-6766 exhibited antitumor activity across several pediatric cancers. As single agent, there was activity in the majority of solid tumor models tested with prolongation of time on study and stabilization of disease. Solid tumor models harboring RAS mutations appear more likely to respond, although limited non-mutant models were tested."

Preclinical • Hematological Malignancies • Leukemia • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • HRAS • KRAS • NF1 • NRAS • PIK3CD

LCD: Lung Cancer With Copanlisib and Durvalumab (clinicaltrials.gov) - P1 | N=11 | Completed | Sponsor: Zhonglin Hao | Active, not recruiting ➔ Completed

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

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: Aug 2025 ➔ Feb 2027

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

biomarker Driven Strategies for Targeted Elimination of Hypoxia Adapted Lymphoma Cells (ASH 2023) - "Sensitivity of HA cells to 2-deoxyglucose, an inhibitor of glycolysis was markedly increased (Figure 1)...Sensitivity of HA cells to a panel of the tested cytotoxic drugs (cytarabin, cisplatin, bortezomib) and targeted agents (venetoclax, S63545, A1155463, TRAIL, polatuzumab vedotin, IM-156, copanlisib) was either unchanged or increased (compared to sensitivity of the original cell lines cultured under normoxia)...In translation, P4HA1, BCL-XL, and structural proteins of the glycolytic pathway may represent novel drugable targets for more effective elimination of hypoxia-adapted lymphoma cells. Financial Support: Ministry of Health of the Czech Republic AZV NU23-03-00172, Grant Agency of the Czech Republic GA23-05377S, and National Institute for Cancer Research (EXCELES) LX22NPO5102."

Biomarker • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2L1 • P4HA1

Phase Ib study of copanlisib, a pan PI3K inhibitor, in combination with ibrutinib, a BTK inhibitor, in relapsed or refractory primary CNS lymphoma (WFNOS 2025) - "Prior treatments included methotrexate (MTX) (n=18), ibrutinib (n=6), radiation (n=2), and transplant (n=5). Eighteen patients were enrolled; 14 to concurrent therapy, 4 sequential. Median age was 63 (range, 40-80), ECOG 1 (0-2), 10 women, 4 men. Patients had a median of 2 prior treatments (range, 1-10) and 11 (61%) were chemo-refractory."

Combination therapy • P1 data • Cardiovascular • CNS Lymphoma • Diabetes • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Primary Central Nervous System Lymphoma • Respiratory Diseases • Thrombocytopenia • CYP3A4

Phase Ib study of copanlisib, a pan PI3K inhibitor, in combination with ibrutinib, a BTK inhibitor, in relapsed or refractory primary CNS lymphoma (SNO 2025) - "Prior treatments included methotrexate (MTX) (n=18), ibrutinib (n=6), radiation (n=2), and transplant (n=5). Eighteen patients were enrolled; 14 to concurrent therapy, 4 sequential. Median age was 63 (range, 40-80), ECOG 1 (0-2), 10 women, 4 men. Patients had a median of 2 prior treatments (range, 1-10) and 11 (61%) were chemo-refractory."

Combination therapy • P1 data • Cardiovascular • CNS Lymphoma • Diabetes • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Primary Central Nervous System Lymphoma • Respiratory Diseases • Thrombocytopenia • CYP3A4

Targeting Epigenetic Resistance Mechanisms to PI3 Kinase Inhibition in Leukemic Stem Cells (ASH 2023) - "We found that dual inhibition with copanlisib and the EZH1/2 inhibitor valemetostat leads to a combinatorial effect to strongly decrease the proliferation of AML cell lines and AML patient samples. Overall, our data suggests that PI3K plays an important role in leukemic stem cells, and that EZH2 downregulation is a non-genetic mechanism of resistance to PI3K inhibition. Additionally, our findings indicate that combining PI3K inhibitors with EZH1/2 dual inhibitors could be a promising therapeutic approach to reduce LSCs, prevent resistance, and prolong survival in AML patients."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • EZH2 • HOXA9 • KMT2A • MEIS1 • PIK3CA

The Role of PI3K Inhibition in Suppressing Pancreatic Cancer Progression: Mechanistic Insights From Copanlisib Studies. (PubMed, Arch Pharm (Weinheim)) - "Collectively, these findings provide preliminary validation for the concept that PI3K inhibitor copanlisib significantly inhibits pancreatic cancer cell proliferation and tumor growth in both in vitro and in vivo settings, promoting apoptosis and suppressing the PI3K signaling pathway, which indicates its potential in pancreatic cancer treatment. We anticipate that these findings will serve as a reference for the clinical application of PI3K inhibitors in managing pancreatic cancer."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Phase I Study of Copanlisib and Venetoclax in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (ASH 2023) - P1/2 | "Copanlisib plus venetoclax is feasible and safe in pts with R/R DLBCL, with no DLTs observed. While it is possible that copanlisib plus venetoclax is active in select genomic subgroups of DLBCL, there was limited activity in this unselected, heavily pre-treated patient population."

Clinical • IO biomarker • P1 data • B Cell Lymphoma • Cardiovascular • Diabetes • Diffuse Large B Cell Lymphoma • Fatigue • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Hypertension • Lymphoma • Metabolic Disorders • Musculoskeletal Diseases • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

BrUOG360: A phase Ib/II study of copanlisib in combination with rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). (PubMed, Cancer Res Commun) - "Copa/R had a favorable safety profile with a signal of efficacy supporting future studies of PARPi with PI3Ki."

Journal • P1/2 data • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • FANCA • PTEN • RAD51C

Pooled Exposure-Response (ER) and Quantitative Benefit/Risk (B/R) Analyses Support the Approved Copanlisib Intermittent Dosing Regimen (ASH 2023) - "The pivotal studies, CHRONOS-1 and CHRONOS-3, established the benefit/risk of copanlisib 60 mg on Day 1, 8, 15 of 28-day cycle as monotherapy in 3L+ relapsed follicular lymphoma and in combination with rituximab in 2L+ non-Hodgkin's lymphoma, respectively. The completed quantitative analyses substantiate the favorable B/R for the copanlisib 60 mg on days 1, 8, and 15 of a 28-day cycle dosing regimen."

Cardiovascular • Diabetes • Fatigue • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • PIK3CA

A Systematic Literature Review (SLR) and Meta-Analysis of Clinical Evidence of Second Line or Later (2L+) Treatments for Follicular Lymphoma (FL) in Adult Patients (ASH 2023) - "Eligible treatments included CAR T cell therapies (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel), T cell engagers (mosunetuzumab, glofitamab, epcoritamab, odronextamab), phosphatidylinositol 3-kinase (PI3K) inhibitors (copanlisib, duvelisib, idelalisib), HSCT, yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, and conventional therapies (immunochemotherapies, single- or multiagent chemo- or immunotherapies, and alkylating agents). This SLR demonstrated an evolving FL treatment landscape, with new agents such as CAR T cell therapies and T cell engagers exhibiting potential for improving effectiveness of treatment for patients in 3L+, 4L+, and 2L+ POD24 populations."

Retrospective data • Review • Bone Marrow Transplantation • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Copanlisib in Combination with Nivolumab in Subjects with Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Primary Mediastinal Large B-Cell Lymphoma: A Phase II Study (ASH 2023) - P2 | "C-N combination had modest clinical activity in pts with R/R DLBCL with some prolonged responses. However, due to the relatively high number of cardiac events and the changing therapeutic landscape with recent approvals, a decision was made to halt the study. These findings likely reflect possibly older and sicker patient population."

Clinical • Combination therapy • IO biomarker • P2 data • Atrial Fibrillation • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Primary Mediastinal Large B-Cell Lymphoma • PIK3CA

Safety, Efficacy and T-Cell Predictive Biomarkers in a Phase I Trial of Copanlisib+Nivolumab in Patients with Richter's Transformation (RT) or Transformed Non-Hodgkin Lymphoma (tNHL) (ASH 2023) - P1 | "Downregulation of MYC in the tumor, activation of the apoptotic program in Tregs and enhanced CD8 T-cell IFN response were associated with treatment response in RT. Accrual is ongoing."

Biomarker • Clinical • IO biomarker • P1 data • Anemia • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Thrombocytopenia • Waldenstrom Macroglobulinemia • CD8 • CTLA4 • MYC • PD-1 • PIK3CA

Copanlisib in Combination with Rituximab and Bendamustine for Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: Results from the Phase II Multicenter Fil_Copa-Rb Trial from Fondazione Italiana Linfomi (FIL) (ASH 2023) - "Copa-RB study was conducted in a difficult-to treat R/R DLBCL cohort (elderly, advanced stage) during COVID pandemic that affected its management. Copa-RB induced a good ORR, but it was short lasting with unfavorable safety profile, so the overall activity was modest and did not support further the development of this combination in this setting of patients. A subset of patients had a long-lasting response."

Clinical • Combination therapy • IO biomarker • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Thrombocytopenia • Transplantation

Preliminary Analysis of an Ongoing Phase II Study of Response-Adapted Therapy with Copanlisib and Rituximab for Untreated Follicular Lymphoma (ASH 2023) - P2 | "CRs were observed in pts deemed high-risk by the GEP assay and FLIPI score. The safety profile is excellent, with mostly G1-2 toxicities manageable with supportive care."

P2 data • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hepatitis B • Human Immunodeficiency Virus • Immunology • Infectious Disease • Lymphoma • Mucositis • Neutropenia • Oncology • PIK3CA

MODULE 1: Evolving Role of Novel Treatment Strategies in Follicular Lymphoma (FL) (ASH 2023) - "Supported by educational grants from AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Genentech, a member of the Roche Group, Genmab US Inc, Merck and Seagen Inc. Appropriate integration of obinutuzumab into current FL treatment algorithms Long-term clinical trial findings with lenalidomide/rituximab (R2) among patients with treatment-naïve and relapsed/refractory (R/R) FL; current role in clinical practice Efficacy and safety outcomes reported from the Phase III CHRONOS-3 trial evaluating copanlisib with rituximab for R/R FL; current clinical role Key findings with and optimal use of tazemetostat for R/R FL with and without EZH2 mutations Rationale for combining tazemetostat with R2 for FL; early safety run-in data with and ongoing assessment of this combination among patients who have received 1 or more prior systemic therapies in the Phase Ib/III SYMPHONY-1 trial Other promising novel agents and strategies under investigation for newly diagnosed and R/R FL"

Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Final Update of Safety, Efficacy and T-Cell Predictive Biomarkers from a Phase I Trial of Copanlisib+Nivolumab in Patients with Richter's Transformation (RT) or Transformed Non-Hodgkin Lymphoma (tNHL) (ASH 2024) - P1 | "COPA 45 mg IV on days 1, 8 and 15 was the MTD/RP2D. Downregulation of MYC in the tumor and enhanced T-cell IFN signaling following treatment were associated with response in RT."

Biomarker • Clinical • IO biomarker • P1 data • Anemia • CNS Disorders • Diabetes • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Musculoskeletal Pain • Neutropenia • Non-Hodgkin’s Lymphoma • Pain • Respiratory Diseases • Richter's Syndrome • Thrombocytopenia • Waldenstrom Macroglobulinemia • CD4 • CD8 • CTLA4 • IFNA1 • IFNG • MYC • PIK3CA

Exploiting TCF3-Driven Oncogenic Circuits in Burkitt Lymphoma (ASH 2024) - "Subsequently, we targeted the BCR signaling cascade with inhibitors of proximal BCR signaling, including the PI3Kα/δ inhibitor copanlisib, and demonstrated sensitivity in all cell lines with functional BCR...Most interestingly, using three novel patient-derived xenograft models of BL patients in NOD SCID gamma (NSG) mice, we demonstrated that a combination of the CD20- and CD38-directed mAbs, rituximab and daratumumab, significantly decreases tumor growth and increased overall survival of NSG mice compared to mice single agent treated or vehicle control...Our functional genomics-based study revealed proximal inhibitors of BCR signaling and anti-CD38 antibodies as druggable TCF3-driven transcriptional targets in BL warranting further clinical testing. Finally, this study highlights the relevance of the approach to search for druggable downstream targets of undruggable, genetically-driven upstream regulators, which can also be applied to other diseases."

IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Mediastinal B Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • Waldenstrom Macroglobulinemia • CD20 • CD79A • CD79B • IGH • MYC • PIK3CA • TCF3

Unbiased combination screening on repurposed drugs reveals synergistic potential of copanlisib and cerivastatin against chemoresistant high-grade serous ovarian cancer. (PubMed, J Ovarian Res) - "This study demonstrates the application of multiplex drug combination screening to identify effective synergistic therapies. Co-targeting PI3-kinase and HMG-CoA reductase could be repurposed as a potent combination to treat chemoresistant HGSOC."

Journal • Platinum resistant • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

Phase Ib study of copanlisib, a pan PI3K inhibitor, in combination with ibrutinib, a BTK inhibitor, in relapsed or refractory primary CNS lymphoma (WFNOS 2025) - "Prior treatments included methotrexate (MTX) (n=18), ibrutinib (n=6), radiation (n=2), and transplant (n=5). Eighteen patients were enrolled; 14 to concurrent therapy, 4 sequential. Median age was 63 (range, 40-80), ECOG 1 (0-2), 10 women, 4 men. Patients had a median of 2 prior treatments (range, 1-10) and 11 (61%) were chemo-refractory."

Combination therapy • P1 data • Cardiovascular • CNS Lymphoma • Diabetes • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Primary Central Nervous System Lymphoma • Respiratory Diseases • Thrombocytopenia • CYP3A4

Copanlisib in combination with venetoclax in patients with relapsed/refractory mantle cell lymphoma. (PubMed, Leuk Lymphoma) - No abstract available

Journal • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology