Aliqopa (copanlisib) / Bayer - LARVOL DELTA

IL-1-driven signaling promotes resistance to PI3K and BCL2 inhibitors in B-cell lymphoma preclinical models (AACR 2026) - "A 1,400-compound FDA-approved library was used in combination with copanlisib/venetoclax. VL51 cells with acquired resistance to PI3K/BCL2 inhibitors were characterized by an upregulation of IL1α and IL1β, elevated ERK and STAT3 phosphorylation, and increased expression of pro-survival and cytokine-responsive proteins. IL-1-driven reprogramming promotes resistance to PI3K and BCL2 inhibition in B-cell lymphoma via activation of NF-κB, STAT3, and metabolic survival pathways. Targeting IL-1 signaling or downstream effectors may overcome resistance and offer a promising therapeutic strategy for relapsed or refractory B-cell lymphomas."

IO biomarker • Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALDH1A1 • AURKA • IL1A • IL1B

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

Targeting insulin to improve endometrial cancer (AACR 2026) - "By employing diazoxide and canagliflozin, pharmacological agents that counteract hyperinsulinemia, we can decrease insulin levels in the tumor while enhancing the apoptotic response to the PI3K inhibitors copanlisib and alpelisib. Additionally, we show that ketogenic diet reduces systemic insulin and improves efficacy of PI3K inhibition in xenograft models of endometrial cancer. These findings have significant implications for ongoing clinical trials of PI3K pathway inhibitors and suggest a method for increased treatment efficacy in cancer patients."

Tumor mutational burden • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer • PIK3CA • PTEN • TMB

Pharmacokinetics of a series of anticancer agents in immunodeficient female NOD scid gamma mice (AACR 2026) - "These PK data are critical for understanding the antitumor activities of agents studied by the PDXNet and will aid investigators in developing new approach methodologies for preclinical safety studies in preparation for human clinical trials."

PK/PD data • Preclinical • Oncology • BCL2 • CDK4 • FGFR • MAP2K1 • PARP1

PIK3CA and ARID1A co-altered tumors are sensitive to AKT inhibitor, capivasertib (AACR 2026) - "These cancers had enhanced sensitivity to PI3K inhibition with copanlisib (cop) in the MATCH trial arm Z1F. PIK3CA and ARID1A co-altered tumors have enhanced sensitivity to capi relative to PIK3CA mutant tumors, potentially through induction of Bims. Capi should be investigated further clinically in PIK3CA and ARID1A co-altered cancers. Additionally, further studies identifying novel drug combinations with capi are warranted to further enhance patient response"

Colorectal Cancer • Oncology • Solid Tumor • AKT1S1 • ARID1A • BCL2L1 • CASP3 • MCL1 • PIK3CA • RPS6

Pharmacoscopy in soft tissue sarcoma, a single-cell ex vivo drug response testing platform (Sarcoma-RC 2026) - "Treatment with the PI3K/mTOR inhibitors omipalisib and copanlisib significantly improved survival (P = 0.027 and P = 0.036, respectively) and reduced tumor growth, compared to vehicle treatment. Legal entity responsible for the study The authors. Funding Iten Kohaut Stiftung."

Preclinical • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Identification of Potential Therapeutic Agents for Primary Amebic Meningoencephalitis Using Text Mining and Bioinformatics Analyses. (PubMed, Anal Cell Pathol (Amst)) - "In addition, arsenic trioxide, bortezomib, dasatinib, bosutinib, bevacizumab, paclitaxel, midostaurin, tamoxifen, copanlisib, and pazopanib were identified as potential drugs targeting PAM using PanDrugs software. Our analyses revealed that text mining-related PAM genes were enriched in several pathways, such as peroxisomes and protein localization. We suggest that PAM is linked to other diseases, such as Zellweger's syndrome, leishmaniasis, and periodontitis, and provide potential drugs for effective treatment."

Journal • Atherosclerosis • Cardiovascular • CNS Disorders • Dental Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Malaria • Nephrology • Periodontitis • Rheumatoid Arthritis • Rheumatology

EAY131-Z1G: Testing Copanlisib as Potentially Targeting Treatment in Cancers With PTEN Loss (MATCH - Subprotocol Z1G) (clinicaltrials.gov) - P2 | N=22 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Jan 2027

Trial completion date • Oncology • Solid Tumor • BRAF • HRAS • KRAS • PIK3CA • PTEN

Rational Design of Potent and Orally Efficacious PI3Kα/δ Degrader for PIK3CA Mutant Breast Cancer without Hyperglycemic Liability. (PubMed, J Med Chem) - "This approach enabled the rational design of copanlisib-based PROTACs, with top compound D5 achieving catalytic degradation efficiency (PI3Kα DC50 = 0.05 nM in T47D cells), >10,000-fold degradation selectivity over the PI3Kβ and PI3Kγ isoforms and minimal off-target effects across >7000 profiled proteins...Orally administered D5 (40 mg/kg) significantly inhibited tumor growth (65% TGI) in xenograft models without inducing metabolic dysregulation. D5 may offer a therapeutic option for human breast cancer harboring the PIK3CA H1047R mutation."

Journal • Breast Cancer • Diabetes • Metabolic Disorders • Oncology • Solid Tumor • Targeted Protein Degradation • PIK3CA • PIK3CB • PIK3CG

EAY131-Z1H: Testing Copanlisib as Potentially Targeting Treatment in Cancers With PTEN Expression (MATCH - Subprotocol Z1H) (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • BRAF • HRAS • KRAS • PIK3CA • PTEN

NCI-2022-06209: Testing Copanlisib as a Potential Targeted Treatment in Cancers With PIK3CA Mutations (MATCH-Subprotocol Z1F) (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Jan 2027

Trial completion date • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • PIK3CA

Continuous Flow Paper Spray Ionization Mass Spectrometry for In-Depth Characterization of Anticancer Drugs in Tissues: Addressing Mass Spectral Complexity. (PubMed, J Am Soc Mass Spectrom) - "Using patient-derived xenograft (PDX) mouse model tissue samples, we observed differential absorption of three anticancer drugs, palbociclib, copanlisib, and olaparib. Tandem mass spectrometric analysis explored the in-source chemical reactivity of these drugs, leading to significant spectral complexity. Our findings highlight the importance of careful spectral interpretation in complex biological matrices and support the development of future rapid quantitative CFPSI analysis of these drugs in tissue samples."

Journal • Oncology

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

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

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

Combination Therapy with Copanlisib and Niraparib in Patients with Recurrent Endometrial and Ovarian Cancer (COPANIRA): Efficacy, Toxicity, and Translational Insights. (PubMed, Clin Cancer Res) - "The combination of copanlisib and niraparib demonstrated limited tolerability, and the objective response rate was modest. However, functional proteomic analyses identified candidate biomarkers-particularly Akt pathway substrates-which may inform future strategies to optimize PI3K and PARP inhibitor combinations."

Journal • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor

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

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

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

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

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

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

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 | Terminated | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Feb 2027 ➔ Dec 2025 | Active, not recruiting ➔ Terminated; Copanlisib development was discontinued by Bayer following withdrawal of copanlisib in relapsed follicular lymphoma in November 2023.

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

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