Aliqopa (copanlisib) / Bayer - LARVOL DELTA

BrUOG360: A phase Ib/II study of copanlisib combined with rucaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2022) - P1/2 | " Enrollment criteria included progressive mCRPC, prior androgen inhibitors (abiraterone, enzalutamide, and/or apalutamide); prior taxane chemotherapy was allowed...Seven pts (63%) received prior chemotherapy (docetaxel [7], cabazitaxel [3])... The combination of rucaparib and copanlisib is well tolerated. The RP2D was rucaparib 400mg BID with copanlisib 45mg (D1, D15; 28-day cycle) with signal of efficacy. Enrollment in a phase 2 expansion cohort in HR-mutated mCRPC is ongoing."

Clinical • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • FANCA • PALB2

BrUOG360: A phase Ib/II study of copanlisib combined with rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) (AACR 2023) - P1/2 | "We describe preliminary results of a phase Ib/II study investigating safety of the combination of copanlisib (pan-class I PI3Ki) and rucaparib (PARP-1, -2 and -3 inhibitor). Enrollment criteria included progressive mCRPC, prior androgen inhibitors (abiraterone, enzalutamide, and/or apalutamide); prior taxane chemotherapy was allowed...Nine patients (69%) received prior chemotherapy (docetaxel [6], cabazitaxel [3])... The combination of rucaparib and copanlisib is well tolerated. The RP2D was rucaparib 400mg BID with copanlisib 45mg (D1, D15; 28-day cycle) with signal of efficacy in patients with and without HRD. Clinical trial information: NCT04253262."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA1 • BRCA2 • CDK12 • FANCA • PALB2

CHRONOS-4: Phase 3 study of copanlisib plus rituximab-based immunochemotherapy in relapsed indolent B-cell lymphoma. (PubMed, Blood Adv) - P3 | "Patients (n=524) were randomized (1:1) to copanlisib (60 mg IV) plus immunochemotherapy (rituximab and bendamustine [R-B] or placebo plus R-B). Overall, copanlisib plus R-B did not provide clinical benefit versus placebo plus R-B and was associated with worse tolerability in patients with relapsed iNHL. ClinicalTrials.gov: NCT02626455."

Clinical • Journal • P3 data • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Lymphoma • Non-Hodgkin’s 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

Safety and efficacy of copanlisib in combination with nivolumab: a Phase Ib study in patients with advanced solid tumors. (PubMed, Cancer Res Commun) - "No new safety concerns were identified with this combination, and preliminary efficacy indicated an anti-tumor effect. Data supported an immunomodulatory effect of copanlisib, suggesting that this combination may enhance the efficacy of ICIs."

IO biomarker • Journal • P1 data • Bladder Cancer • Oncology • Solid Tumor

A phase 1 trial of copanlisib plus ibrutinib in relapsed/refractory mantle cell lymphoma. (PubMed, Blood Adv) - No abstract available

Journal • P1 data • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. (PubMed, Lancet Oncol) - P1/2 | "Fixed-duration mosunetuzumab has a favourable safety profile and induces high rates of complete remissions, allowing potential administration as an outpatient regimen, in patients with relapsed or refractory follicular lymphoma and two or more previous therapies."

Journal • P2 data • Diabetes • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Inflammation • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Renal Disease

Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "Copanlisib plus rituximab improved progression-free survival in patients with relapsed indolent non-Hodgkin lymphoma compared with placebo plus rituximab. To our knowledge, copanlisib is the first PI3K inhibitor to be safely combined with rituximab and the first to show broad and superior efficacy in combination with rituximab in patients with relapsed indolent non-Hodgkin lymphoma."

Clinical • Journal • P3 data • Diabetes • Hematological Malignancies • Hypertension • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia

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

COPANIRA: Phase Ib trial of copanlisib (PI3K inhibitor) and niraparib (PARP inhibitor) in recurrent ovarian and endometrial cancer (SGO 2024) - P1 | "The combination of copanlisib and niraparib was not well tolerated. Although clinical benefit was achieved in a moderate proportion of patients, the ORR was low. Assessment of molecular correlates of response and resistance is ongoing."

P1 data • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA

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

Phase II Study of Copanlisib in Patients With Tumors With PIK3CA Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F. (PubMed, J Clin Oncol) - "The study met its primary end point with an ORR of 16% (P = .0341) with copanlisib showing clinical activity in select tumors with PIK3CA mutation in the refractory setting."

Journal • P2 data • Breast Cancer • Diabetes • Fatigue • Gastrointestinal Disorder • Hematological Malignancies • HER2 Positive Breast Cancer • Hypertension • Lymphoma • Oncology • Solid Tumor • HER-2 • KRAS • PIK3CA • PTEN

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: Aug 2026 ➔ Jul 2027

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

Testing the Combination of Copanlisib, Nivolumab and Ipilimumab in Patients With Advanced Cancer and Lymphoma (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Aug 2027 | Trial primary completion date: Jul 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

COPA-R-CHOP: Copanlisib in Combination With Rituximab and CHOP Chemotherapy in Patients With Previously Untreated DLBCL (clinicaltrials.gov) - P2 | N=62 | Completed | Sponsor: University Hospital Muenster | Active, not recruiting ➔ Completed

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

Sex-Specific Safety Profiles of PI3K Inhibitors: A Real-World Pharmacovigilance Study Based on FAERS Database. (PubMed, Clin Ther) - "This research identifies sex-specific AE patterns for PI3K inhibitors. Subsequent to FDR correction, significant PT level sex differences were detected for alpelisib, yet not for idelalisib. Moreover, no differences at the standard of care SOC level persisted for either drug. The findings regarding copanlisib and duvelisib remain indeterminate. These results provide clinically relevant signals for sex-tailored AE surveillance and necessitate prospective validation."

Adverse events • Journal • Real-world evidence • Diabetes

Copanlisib in combination with nivolumab formicrosatellite stable colorectal cancer: a phase 1/2 trial. (PubMed, Nat Commun) - P1/2 | "Secondary endpoints are median progression-free survival (Cohort A: 1.7 months; Cohort B: 1.6 months), median overall survival (Cohort A: 8.5 months; Cohort B: 6.7 months), duration of response (Cohort A: 13.1 months; Cohort B: 17 months) and 6-month disease control rate (Cohort A: 2/17; Cohort B: 3/22). Secondary endpoints were not statistically different between these cohorts."

IO biomarker • Journal • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor • PIK3CA

Clinical outcomes of the chemo-free approach in relapsed/refractory follicular lymphoma: A network meta-analysis. (PubMed, Br J Haematol) - "Epcoritamab plus rituximab (R2) achieved the top SUCRA rankings for OS, PFS and ORR, while tafasitamab plus R2 consistently ranked second, with a better safety profile. R2 alone showed intermediate efficacy and good tolerability, whereas zanubrutinib plus anti-CD20 demonstrated modest efficacy with lower toxicity. Bortezomib and copanlisib-based combinations ranked lowest for efficacy, with phosphoinositide 3-kinase (PI3K) inhibitor-based regimens showing the least favourable benefit-risk profile...This NMA indicates that immune-centric, anti-CD20-anchored combinations represent the most effective chemotherapy-free strategies for R/R FL. Combinations incorporating anti-CD19 or CD20/CD3 bispecific antibodies appear to offer deeper disease control, particularly in high-risk and rituximab-refractory disease."

Clinical data • Journal • Retrospective data • Review • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Combined inhibition of CDK4/6 and PI3K pathways exhibit highly synergistic activity and translational potential in Ewing sarcoma. (PubMed, Transl Oncol) - "The results of the screen revealed that a PI3K inhibitor, copanlisib, combined with a CDK4/6 inhibitor, ribociclib, exhibited strong synergistic anti-Ewing sarcoma activity. In two xenograft models of Ewing sarcoma, we demonstrated that the combination significantly prolonged survival compared to treatment with either vehicle or single-agent therapy alone. Our findings identify a new candidate therapy combination for Ewing sarcoma and provide a resource of additional potential synergistic combinations for future validation."

Journal • Ewing Sarcoma • Oncology • Pediatrics • Sarcoma • Solid Tumor • CDK4 • EWSR1 • FLI1

Machine learning-driven identification of pan-PI3K inhibitors: A hybrid virtual screening approach combining naïve Bayesian classification, pharmacophore modeling, and consensus scoring-based molecular docking. (PubMed, Biophys Chem) - "The VS method was validated for its strong predictive accuracy by successfully identifying the commercially available pan-PI3K inhibitor copanlisib. The hybrid VS strategy was applied to the SPECS database, leading to the discovery of several promising PI3K inhibitor compounds. The machine learning-based VS approach is expected to offer meaningful insights and a practical framework for discovering novel PI3K inhibitors."

Journal • Oncology

Chaperone-Mediated Autophagy-Directed Degradation of PI3K in Tumor Cells: Development of Multifunctional Peptide-Drug Conjugates With Enhanced Penetration and Selectivity. (PubMed, Arch Pharm (Weinheim)) - "In vivo experiments using NCI-H460 xenograft models demonstrated that TCCC-1 achieved up to 97.0% tumor suppression at high doses, surpassing the efficacy of Copanlisib, without causing significant systemic toxicity, organ damage, or metabolic disturbances such as hyperglycemia. These results highlight TCCC-1 as a promising therapeutic candidate that leverages CMA for precise PI3K degradation, offering enhanced penetration and selectivity against tumors."

Journal • Diabetes • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Niraparib and Copanlisib in Treating Patients With Recurrent Endometrial, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: Dec 2026 ➔ Jun 2026 | Trial primary completion date: Dec 2026 ➔ Jun 2026

Platinum resistant • Platinum sensitive • Trial completion • Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA • MUC16

Donor-specific toxicity of copanlisib identified using immune-humanized mice. (PubMed, Cancer Immunol Immunother) - "However, analysis of the histopathology by donor revealed clear differences, with one donor showing significant pathology, regardless of treatment dose or route, while the other two donors showed little to no adverse treatment effects. Flow cytometric analysis showed the affected donor had significantly more activated T-cells present in the bone marrow regardless of dose or route of administration.Although our findings represent only one of three donors used in immune-humanized mice, this study suggests that some immune modulating therapeutic toxicity could be associated with specific genetic factors from individual patients rather than being dose related."

Journal • Preclinical • Follicular Lymphoma • Hematological Malignancies • Inflammation • Lymphoma • Oncology

Bone Marrow Stromal Cells Drive Resistance to B-Cell Receptor Signaling Targeted Agents in B-Cell Non-Hodgkin Lymphoma (EACR 2026) - "Targeting IL-6 with sirukumab, partially rescued VL51 sensitivity in the co-culture to copanlisib and, to a lesser extent, to ibrutinib. We established a novel 3D co-culture model that recapitulates the interactions between B-cell lymphoma and the BM microenvironment. Our findings demonstrate that BMSCs reduce the sensitivity of lymphoma cell lines to copanlisib and ibrutinib and identify IGFBP-3, Serpin E1, and PTX-3 as potential secreted mediators of resistance. This platform provides a novel scalable system for investigating resistance mechanisms to clinically relevant therapies."

Stroma • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • IGFBP3 • IL6 • PTX3

Combination Treatment Targeting Cancer Stem Cell Subpopulation Reverting Chemoresistance in Germ Cells Tumors (EACR 2026) - "Material and A broad panel of parental and cisplatin-resistant (CisR) isogenic GCT cell lines was analyzed for TACSTD2 (TROP-2) expression by RT-qPCR, and sensitivity to sacituzumab govitecan was assessed at day 3 using an endpoint luminescence assay. To explore strategies for overcoming chemoresistance, combination treatments were performed with a panel of targeted pathway inhibitors affecting cell cycle, DNA damage response, transcriptional regulation, and oncogenic signaling (Tuvusertib [CDK7 inhibitor], Ceralasertib [ATR inhibitor], Adavosertib [WEE1 inhibitor], Simvastatin, Copanlisib, ABVV-744, Cyclosporin A, Dasatinib, Crizotinib, Tozasertib, Alpelisib, Selumetinib) to evaluate potential synergistic effects.Result and We focused on the transmembrane glycoprotein TROP-2 (trophoblast cell surface antigen 2), involved in proliferation, migration, and invasiveness, which is overexpressed in multiple solid tumors... Our findings support further investigation of..."

Cancer stem • Clinical • Germ Cell Tumors • Oncology • Solid Tumor • Testicular Cancer • TACSTD2