Aliqopa (copanlisib) / Bayer - LARVOL DELTA

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

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 • Hematological Malignancies • Lymphoma

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

Alpha-enolase influences ATP pool of cytoplasm and lactate homeostasis by regulating glycolysis in gastric cancer. (PubMed, Signal Transduct Target Ther) - "Furthermore, pharmacological studies revealed that metformin combined with copanlisib significantly inhibited tumors by blocking the energy metabolism pathways PI3K/AKT and AMPK/mTOR. Rationally, targeting multiple nodes along the ENO1-ATP/lactate-AMPK/PI3K/AKT-mTOR axis may be effective for GC treatment, as indicated by the significant suppression of tumor growth by metformin (which inhibits ATP production) plus syrosingopine (which disrupts lactate homeostasis). In conclusion, the complex interplay between metabolism and tumor stemness offers novel therapeutic directions and potential treatment strategies for GC."

Biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • ENO1

Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Jan 2027 ➔ Sep 2025

Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Durvalumab and copanlisib combination in unresectable stage III NSCLC consolidation with exceptional PFS (ESMO 2025) - P1 | "Legal entity responsible for the study University of Kentucky, Markey Cancer Center, USA. Funding Markey Cancer Center."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PIK3CD

NCI10217: Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov) - P1 | N=39 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Sep 2026

Biomarker • Trial completion date • Oncology • Solid Tumor • BARD1 • BRCA1 • BRCA2 • BRIP1 • CD4 • FANCA • NBN • PIK3CA • RAD51 • RAD51B • RAD51C • RAD51D

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov) - P2 | N=6452 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Biomarker • Trial completion date • Trial primary completion date • Bladder Cancer • Brain Cancer • Breast Cancer • Cervical Cancer • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Hematological Malignancies • Hormone Receptor Positive Breast Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Refractory Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Thyroid Gland Carcinoma • Uterine Cancer • CD4 • MSI

Testing the Addition of Copanlisib to Usual Treatment (Fulvestrant and Abemaciclib) in Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2024 ➔ Aug 2026 | Completed ➔ Active, not recruiting

Enrollment closed • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR • PIK3CA • PTEN

CA209-8LC: Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=48 | Completed | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting ➔ Completed

Mismatch repair • pMMR • Trial completion • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS

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

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

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