Aliqopa (copanlisib) / Bayer - LARVOL DELTA

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

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

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

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

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 (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

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

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

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

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

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

Copanlisib Plus Venetoclax in R/R DLBCL (clinicaltrials.gov) - P1/2 | N=48 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Apr 2026 ➔ Jul 2026 | Trial primary completion date: Apr 2026 ➔ Jul 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

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: Nov 2025 ➔ Nov 2026 | Trial primary completion date: Nov 2025 ➔ Nov 2026

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

Copanlisib Plus Venetoclax in R/R DLBCL (clinicaltrials.gov) - P1/2 | N=48 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Dec 2025 ➔ Apr 2026 | Trial primary completion date: Oct 2025 ➔ Apr 2026

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

Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN (clinicaltrials.gov) - P1/2 | N=54 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=102 ➔ 54 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Oct 2025

Biomarker • Checkpoint inhibition • Enrollment change • IO biomarker • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • PD-L1 • PIK3CA • PTEN

Representation of Older Adults in Registrational Trials Associated with Therapeutic Approvals in Follicular Lymphoma (SIOG 2025) - "FL trials had low OA enrolment, with inadequate reporting and participation of adults over 75 yrs. Enhanced age subgroup reporting and OA enrolment are needed to ensure that trial outcomes are more representative of the broader patient population, particularly the elderly, who are most affected by FL."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Representation of Older Adults in Registrational Trials Associated with Therapeutic Approvals in Follicular Lymphoma (SIOG 2025) - "FL trials had low OA enrolment, with inadequate reporting and participation of adults over 75 yrs. Enhanced age subgroup reporting and OA enrolment are needed to ensure that trial outcomes are more representative of the broader patient population, particularly the elderly, who are most affected by FL."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Representation of Older Adults in Registrational Trials Associated with Therapeutic Approvals in Follicular Lymphoma (SIOG 2025) - "FL trials had low OA enrolment, with inadequate reporting and participation of adults over 75 yrs. Enhanced age subgroup reporting and OA enrolment are needed to ensure that trial outcomes are more representative of the broader patient population, particularly the elderly, who are most affected by FL."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Representation of Older Adults in Registrational Trials Associated with Therapeutic Approvals in Follicular Lymphoma (SIOG 2025) - "FL trials had low OA enrolment, with inadequate reporting and participation of adults over 75 yrs. Enhanced age subgroup reporting and OA enrolment are needed to ensure that trial outcomes are more representative of the broader patient population, particularly the elderly, who are most affected by FL."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

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

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