^
    8d
    Testing the Addition of Copanlisib to Usual Treatment (Fulvestrant and Abemaciclib) in Metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=24, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P1/2 --> P1 | Trial completion date: Mar 2025 --> Jul 2025
    Phase classification • Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog)
    |
    HER-2 amplification • HER-2 negative • PGR positive • HER-2 negative + PGR positive
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    |
    Verzenio (abemaciclib) • fulvestrant • Aliqopa (copanlisib)
    2ms
    A Study of Copanlisib in Combination with Degarelix in People with Prostate Cancer (clinicaltrials.gov)
    P1/2, N=0, Withdrawn, Memorial Sloan Kettering Cancer Center | N=37 --> 0 | Active, not recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • Combination therapy
    |
    Aliqopa (copanlisib) • Firmagon (degarelix)
    2ms
    A Study to Learn More About Copanlisib Treatment Patterns in People With Indolent Non-Hodgkin Lymphoma, a Type of Cancer That Grows and Spread Slowly and Develops in the Lymphatic System (a Part of Immune System) in Taiwan Under Real-word Conditions (clinicaltrials.gov)
    P=N/A, N=6, Completed, Bayer | Active, not recruiting --> Completed | N=50 --> 6
    Trial completion • Enrollment change
    |
    Aliqopa (copanlisib)
    2ms
    A Study of Copanlisib in Combination with Degarelix in People with Prostate Cancer (clinicaltrials.gov)
    P1/2, N=37, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy
    |
    Aliqopa (copanlisib) • Firmagon (degarelix)
    3ms
    Dose De-escalation Study of the PI3k Alpha/Delta Inhibitor, Copanlisib Given in Combination With the Immunotherapeutic Agents, Nivolumab and Rituximab in Patients With Relapsed/Refractory Indolent Lymphoma (clinicaltrials.gov)
    P1, N=6, Terminated, University of Michigan Rogel Cancer Center | N=35 --> 6 | Trial completion date: Jun 2026 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Nov 2023; Loss of study funding
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    Opdivo (nivolumab) • Rituxan (rituximab) • Aliqopa (copanlisib)
    3ms
    Depside and depsidone-rich hydroalcoholic extract, resourced from the lichen Parmelinella wallichiana (Taylor) Elix & Hale selectively restricts non-small cell lung Cancer by modulating p53, FOXO1 and PALLADIN genes. (PubMed, Fitoterapia)
    Then, an in silico docking with these lichen-derived metabolites against the PI3Kα receptor predicted these compounds has a binding affinity close to a standard PI3Kα inhibitor copanlisib. The study concludes that the extract restricts lung cancer possibly through the PI3Kα/FOXO1 axis and thus Parmelinella wallichiana represents a potential resource for anti-lung cancer drug development in future.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BAX (BCL2-associated X protein)
    |
    BAX expression
    |
    Aliqopa (copanlisib)
    4ms
    FIL_Copa-RB: Copanlisib With Rituximab-Bendamustine in Patients With Relapsed-Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov)
    P2, N=37, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Aug 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • BCL6 (B-cell CLL/lymphoma 6)
    |
    Rituxan (rituximab) • Aliqopa (copanlisib) • bendamustine
    5ms
    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: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    Opdivo (nivolumab) • Aliqopa (copanlisib)
    5ms
    Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA adverse event reporting system. (PubMed, Expert Opin Drug Saf)
    Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibitingPI3Kδ) were developed to target the PI3K pathway...The safety profiles of the five PI3K inhibitorsvary concerning adverse events. These findings could guide drug selection andinform future prospective research.
    P4 data • Journal • Adverse events
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
    |
    Piqray (alpelisib) • Aliqopa (copanlisib) • Zydelig (idelalisib) • Copiktra (duvelisib) • Ukoniq (umbralisib)
    5ms
    Targeting CD25+ lymphoma cells with the antibody-drug conjugate camidanlumab tesirine as a single agent or in combination with targeted agents. (PubMed, Br J Haematol)
    When camidanlumab tesirine-containing combinations were evaluated in four T-cell lymphoma models, the most active partners were everolimus, copanlisib, venetoclax, vorinostat, and pralatrexate, followed by bortezomib, romidepsin, bendamustine, and 5-azacytidine. The strong camidanlumab tesirine single-agent anti-lymphoma activity and the in vitro synergisms with targeted agents identify potential combination partners for future clinical studies.
    Journal • Combination therapy
    |
    IL2RA (Interleukin 2 receptor, alpha)
    |
    Venclexta (venetoclax) • everolimus • bortezomib • azacitidine • Aliqopa (copanlisib) • Zolinza (vorinostat) • bendamustine • Istodax (romidepsin) • camidanlumab tesirine (ADCT-301) • Folotyn (pralatrexate)
    5ms
    Copanlisib With Dose-Adjusted EPOCH-R in Relapsed and Refractory Burkitt Lymphoma and Other High-Grade B-cell Lymphomas (clinicaltrials.gov)
    P1, N=8, Terminated, National Cancer Institute (NCI) | Completed --> Terminated; The study was terminated early because copanlisib was removed from the market by the Food and Drug Administration (FDA) and the manufacturer.
    Trial termination
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
    |
    Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • Aliqopa (copanlisib) • vincristine • Marqibo (vincristine liposomal)
    6ms
    First-in-class inhibitor of HSP110 blocks BCR activation through SYK phosphorylation in diffuse large B-cell lymphoma. (PubMed, Leukemia)
    Finally, the combination of the HSP110 inhibitor with the PI3K inhibitor copanlisib decreases SYK/BTK and AKT phosphorylation synergistically, leading to suppression of tumor growth in cell line xenografts and strong reduction in patient-derived xenografts. In conclusion, by regulating the BCR/TLR signaling pathway, HSP110 inhibitors are potential drug candidates for ABC-DLBCL patients.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • SYK (Spleen tyrosine kinase) • HSPH1 (Heat Shock Protein Family H (Hsp110) Member 1)
    |
    Aliqopa (copanlisib)
    6ms
    Targeting the RAS upstream and downstream signaling pathway for Cancer treatment. (PubMed, Eur J Pharmacol)
    For instance, RTK inhibitors such as imatinib and afatinib selectively target these receptors, hindering ligand binding and reducing signaling initiation...Other inhibitors, like lonafarnib targeting Farnesyltransferase and GGTI 2418 targeting geranylgeranyl Transferase, disrupt post-translational modifications of proteins...Targeting downstream components with RAF inhibitors such as vemurafenib, dabrafenib, and sorafenib, along with MEK inhibitors like trametinib and binimetinib, has shown promising outcomes in treating cancers with BRAF-V600E mutations, including myeloma, colorectal, and thyroid cancers. Furthermore, inhibitors of PI3K (e.g., apitolisib, copanlisib), AKT (e.g., ipatasertib, perifosine), and mTOR (e.g., sirolimus, temsirolimus) exhibit promising efficacy against various cancers such as Invasive Breast Cancer, Lymphoma, Neoplasms, and hematological malignancies. This review offers an overview of small molecule inhibitors targeting specific proteins within the RAS upstream and downstream signaling pathways in cancer.
    Review • Journal
    |
    BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    Mekinist (trametinib) • Gilotrif (afatinib) • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • sorafenib • imatinib • Mektovi (binimetinib) • Torisel (temsirolimus) • Aliqopa (copanlisib) • ipatasertib (RG7440) • sirolimus • apitolisib (GDC-0980) • perifosine (D21266) • PTX-100
    6ms
    Niraparib and Copanlisib in Treating Patients With Recurrent Endometrial, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov)
    P1, N=31, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    Zejula (niraparib) • Aliqopa (copanlisib)
    6ms
    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 2024 --> Oct 2026 | Trial primary completion date: Aug 2024 --> Oct 2026
    Trial completion date • Trial primary completion date • Combination therapy
    |
    ER (Estrogen receptor) • 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)
    |
    fulvestrant • Aliqopa (copanlisib)
    7ms
    Copanlisib and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov)
    P1/2, N=8, Active, not recruiting, City of Hope Medical Center | Suspended --> Active, not recruiting | N=23 --> 8
    Enrollment closed • Enrollment change
    |
    BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • PAX5 (Paired Box 5) • CD5 (CD5 Molecule)
    |
    Venclexta (venetoclax) • Aliqopa (copanlisib)
    7ms
    Combined inhibition of class 1-PI3K-alpha and delta isoforms causes senolysis by inducing p21WAF1/CIP1 proteasomal degradation in senescent cells. (PubMed, Cell Death Dis)
    The Pan-PI3K-inhibitor wortmannin and its clinical derivative, PX-866, were identified to act as senolytics...Other Pan-PI3K inhibitors, such as the FDA-approved drug BAY80-6946 (Copanlisib, Aliqopa®), also efficiently and specifically eliminated senescent cells. Interestingly, only the simultaneous inhibition of both PI3K class I alpha (with BYL-719 (Alpelisib, Piqray®)) and delta (with CAL-101 (Idelalisib, Zydelig®)) isoforms was sufficient to induce senolysis, whereas single application of these inhibitors had no effect...This led to a timely induction of apoptosis in senescent tumor cells. Taken together, the senolytic properties of PI3K-inhibitors reveal a novel dimension of these promising compounds, which holds particular potential when employed alongside DNA damaging agents in combination tumor therapies.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    Piqray (alpelisib) • Aliqopa (copanlisib) • Zydelig (idelalisib) • sonolisib (PX 866)
    7ms
    CHRONOS-3: Copanlisib and Rituximab in Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL) (clinicaltrials.gov)
    P3, N=458, Active, not recruiting, Bayer | Trial completion date: May 2024 --> Aug 2024
    Trial completion date • Combination therapy
    |
    CD20 positive
    |
    Rituxan (rituximab) • Aliqopa (copanlisib)
    7ms
    Evaluation of copanlisib in combination with eribulin in triple negative breast cancer patient-derived xenograft models. (PubMed, Cancer Res Commun)
    These data support further clinical development for the combination of copanlisib and eribulin. These data led to a phase I/II trial of copanlisib and eribulin in patients with metastatic TNBC.
    Preclinical • Journal • Combination therapy
    |
    PTEN (Phosphatase and tensin homolog)
    |
    Halaven (eribulin mesylate) • Aliqopa (copanlisib)
    8ms
    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)
    New P2 trial
    |
    Aliqopa (copanlisib)
    8ms
    Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix. (PubMed, Proc Natl Acad Sci U S A)
    However, combinations of copanlisib/afatinib and copanlisib/elimusertib were significantly more effective in controlling NETc tumor growth. These findings define the genetic landscape of NETc and suggest that a large subset of these highly lethal malignancies might benefit from existing targeted therapies.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • PVT1 (Pvt1 Oncogene) • RPL10 (Ribosomal Protein L10)
    |
    KRAS mutation • PIK3CA mutation • ARID1A mutation • KMT2D mutation
    |
    Gilotrif (afatinib) • Aliqopa (copanlisib) • elimusertib (BAY 1895344)
    8ms
    Testing Copanlisib as Potentially Targeting Treatment in Cancers With PTEN Loss (MATCH - Subprotocol Z1G) (clinicaltrials.gov)
    P2, N=35, Active, not recruiting, National Cancer Institute (NCI)
    New P2 trial
    |
    Aliqopa (copanlisib)
    9ms
    BrUOG 360: A Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=13, Active, not recruiting, Brown University | Trial completion date: May 2024 --> Jan 2027 | Trial primary completion date: Jan 2024 --> Jan 2027
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRIP1 mutation
    |
    Rubraca (rucaparib) • Aliqopa (copanlisib)
    9ms
    Copanlisib and Avelumab as a Maintenance Therapy for Advanced Bladder Cancer (clinicaltrials.gov)
    P1/2, N=29, Not yet recruiting, VA Office of Research and Development | Phase classification: P2 --> P1/2 | Trial completion date: Jun 2028 --> Dec 2028 | Trial primary completion date: Dec 2027 --> Jun 2028
    Phase classification • Trial completion date • Trial primary completion date • Metastases
    |
    Bavencio (avelumab) • Aliqopa (copanlisib)
    9ms
    Testing the Addition of Copanlisib to Usual Treatment (Fulvestrant and Abemaciclib) in Metastatic Breast Cancer (clinicaltrials.gov)
    P1/2; N=204 --> 24 | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Jun 2023
    Combination therapy • Trial completion date • Trial primary completion date • Enrollment change • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog)
    |
    HER-2 amplification • HER-2 negative • PGR positive
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    |
    Verzenio (abemaciclib) • fulvestrant • Aliqopa (copanlisib)
    9ms
    Alternative-C: 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 (clinicaltrials.gov)
    P2, N=98, Active, not recruiting, Ludwig-Maximilians - University of Munich | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2022 --> Sep 2023
    Enrollment closed • Trial primary completion date • Combination therapy
    |
    Gazyva (obinutuzumab) • Aliqopa (copanlisib)
    10ms
    Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)
    P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual
    Trial termination
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • sunitinib • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical
    10ms
    Vemurafenib Plus Copanlisib in Radioiodine-Refractory (RAIR) Thyroid Cancers (clinicaltrials.gov)
    P1, N=8, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2023
    Trial completion • Trial completion date
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • BRAF V600
    |
    Zelboraf (vemurafenib) • Aliqopa (copanlisib)
    10ms
    Expanded Access to Provide Copanlisib for Patients With Cancer Who Are Experiencing a Positive Response, as Determined by Their Doctors (clinicaltrials.gov)
    P=N/A, N=0, No Longer Available, Bayer
    New trial
    |
    Aliqopa (copanlisib)
    10ms
    LCD: Lung Cancer With Copanlisib and Durvalumab (clinicaltrials.gov)
    P1, N=11, Active, not recruiting, Zhonglin Hao | Recruiting --> Active, not recruiting | N=18 --> 11 | Trial completion date: Jun 2031 --> Jun 2025 | Trial primary completion date: Jun 2031 --> Jun 2025
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    Imfinzi (durvalumab) • Aliqopa (copanlisib)
    11ms
    β1 integrin mediates unresponsiveness to PI3Kα inhibition for radiochemosensitization of 3D HNSCC models. (PubMed, Biomed Pharmacother)
    Here, we investigated the radiochemosensitizing potential and adaptation mechanisms of four PI3K inhibitors, Alpelisib, Copanlisib, AZD8186, and Idelalisib in eight HNSCC models grown under physiological, three-dimensional matrix conditions. Finally, we demonstrate that targeting of the cell adhesion molecule β1 integrin on top of Alpelisib sensitizes non-responders to radiochemotherapy. Taken together, our study demonstrates the sensitizing potential of Alpelisib and other PI3K inhibitors in HNSCC models and uncovers a novel β1 integrin-dependent mechanism that may prove useful in overcoming resistance to PI3K inhibitors.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    Piqray (alpelisib) • Aliqopa (copanlisib) • Zydelig (idelalisib) • AZD8186
    11ms
    Lung Fibroblasts Take up Breast Cancer Cell-derived Extracellular Vesicles Partially Through MEK2-dependent Macropinocytosis. (PubMed, Cancer Res Commun)
    Among the drugs identified to inhibit EV uptake without exerting significant cytotoxicity, we validated the dose-dependent effect of Trametinib (a MEK1/2 inhibitor) and Copanlisib (a PI3K inhibitor). Through a phenotypic screen, we found that MEK inhibitor Trametinib suppressed EV uptake and macropinocytosis in lung fibroblasts, and that EV uptake is mediated by MEK2 in these cells. Our results suggest that MEK2 inhibition could serve as a strategy to block cancer EV uptake by lung fibroblasts.
    Journal
    |
    MAP2K2 (Mitogen-activated protein kinase kinase 2)
    |
    Mekinist (trametinib) • Aliqopa (copanlisib)
    11ms
    A Study of Copanlisib in Combination With Degarelix in People With Prostate Cancer (clinicaltrials.gov)
    P1/2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center
    New P1/2 trial • Combination therapy
    |
    Aliqopa (copanlisib) • Firmagon (degarelix)
    11ms
    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: Oct 2026 --> Aug 2024 | Trial primary completion date: Oct 2026 --> Aug 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    ER (Estrogen receptor) • 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)
    |
    ER positive • PIK3CA mutation • PTEN deletion • PIK3R1 mutation
    |
    fulvestrant • Aliqopa (copanlisib)
    11ms
    Dual targeting of the androgen receptor and PI3K/AKT/mTOR pathways in prostate cancer models improves antitumor efficacy and promotes cell apoptosis. (PubMed, Mol Oncol)
    Combination treatment with the AR inhibitor darolutamide led to enhanced apoptosis in these cell lines, the effects being most pronounced upon cotreatment with the pan-PI3K inhibitor copanlisib. Importantly, immunohistochemistry analysis of these treated tumors showed increased apoptosis, as revealed by elevated levels of cleaved caspase 3 and Bcl-2-binding component 3 (BBC3). In conclusion, these data demonstrate that concurrent blockade of the PI3K/AKT/mTOR and AR pathways has superior antitumor efficacy and induces apoptosis in androgen-sensitive prostate cancer cell lines and PDX models.
    Preclinical • Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • AR (Androgen receptor) • CASP3 (Caspase 3) • CASP7 (Caspase 7) • BBC3 (BCL2 Binding Component 3)
    |
    Aliqopa (copanlisib) • Nubeqa (darolutamide)
    12ms
    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, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 --> Jun 2025
    Trial completion date • Mismatch repair
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • BRAF wild-type • NRAS wild-type
    |
    Opdivo (nivolumab) • Aliqopa (copanlisib)
    12ms
    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 | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Jul 2024 | Trial primary completion date: Dec 2023 --> Jul 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Opdivo (nivolumab) • Aliqopa (copanlisib)
    12ms
    COPA-R-CHOP: Copanlisib in Combination With Rituximab and CHOP Chemotherapy in Patients With Previously Untreated DLBCL (clinicaltrials.gov)
    P2, N=62, Active, not recruiting, University Hospital Muenster | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Apr 2025 | Trial primary completion date: Jun 2024 --> Apr 2025
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
    |
    BCL6 rearrangement • BCL2 rearrangement
    |
    Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • Aliqopa (copanlisib)
    12ms
    Testing the Addition of Copanlisib to Eribulin for the Treatment of Advanced-Stage Triple Negative Breast Cancer (clinicaltrials.gov)
    P1/2, N=106, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog)
    |
    HER-2 amplification • HER-2 negative • PIK3CA mutation • PTEN mutation
    |
    Halaven (eribulin mesylate) • Aliqopa (copanlisib)
    12ms
    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=102, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Checkpoint inhibition • IO biomarker • Metastases
    |
    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 • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Aliqopa (copanlisib) • ABP 206 (nivolumab biosimilar)
    12ms
    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 | Recruiting --> Active, not recruiting | N=78 --> 7
    Enrollment closed • Enrollment change • Combination therapy
    |
    ER (Estrogen receptor) • 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)
    |
    ER positive • PIK3CA mutation • PTEN deletion • PIK3R1 mutation
    |
    fulvestrant • Aliqopa (copanlisib)
    12ms
    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=108, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)