^
    1m
    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
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    PIK3CA mutation
    |
    Aliqopa (copanlisib)
    1m
    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, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027
    Trial completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    Aliqopa (copanlisib)
    1m
    EAY131-Z1G: Testing Copanlisib as Potentially Targeting Treatment in Cancers With PTEN Loss (MATCH - Subprotocol Z1G) (clinicaltrials.gov)
    P2, N=22, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027
    Trial completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
    |
    Aliqopa (copanlisib)
    1m
    EAY131-Z1H: Testing Copanlisib as Potentially Targeting Treatment in Cancers With PTEN Expression (MATCH - Subprotocol Z1H) (clinicaltrials.gov)
    P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026
    Trial completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
    |
    PTEN mutation
    |
    Aliqopa (copanlisib)
    2ms
    Copanlisib With Ibrutinib for Patients With Recurrent/ Refractory Primary Central Nervous System Lymphoma (PCNSL) (clinicaltrials.gov)
    P1/2, N=18, Completed, 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
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    Imbruvica (ibrutinib) • Aliqopa (copanlisib)
    3ms
    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, 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
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PI3K (Phosphoinositide 3-kinases)
    |
    PIK3CA mutation • PTEN deletion
    |
    fulvestrant • Aliqopa (copanlisib)
    3ms
    Copanlisib Plus Venetoclax in R/R DLBCL (clinicaltrials.gov)
    P1/2, N=48, Active, not recruiting, 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
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    BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
    |
    Venclexta (venetoclax) • Aliqopa (copanlisib)
    3ms
    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, 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
    |
    PD-L1 (Programmed death ligand 1)
    |
    Opdivo (nivolumab) • Aliqopa (copanlisib)
    3ms
    Copanlisib Plus Venetoclax in R/R DLBCL (clinicaltrials.gov)
    P1/2, N=48, Active, not recruiting, 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
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
    |
    Venclexta (venetoclax) • Aliqopa (copanlisib)
    4ms
    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, National Cancer Institute (NCI) | N=102 --> 54 | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Oct 2025
    Enrollment change • Trial completion date • Trial primary completion date • Checkpoint inhibition • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation • PTEN mutation
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Aliqopa (copanlisib) • ABP 206 (nivolumab biosimilar)
    4ms
    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, M.D. Anderson Cancer Center | Trial completion date: Aug 2025 --> Feb 2027
    Trial completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PI3K (Phosphoinositide 3-kinases)
    |
    PIK3CA mutation • PTEN deletion
    |
    fulvestrant • Aliqopa (copanlisib)
    5ms
    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.
    P1/2 data • Journal
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C)
    |
    Rubraca (rucaparib) • Aliqopa (copanlisib)