^
2d
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)
4d
Can Duvelisib and Eganelisib work for both cancer and COVID-19? Molecular-level insights from MD simulations and enhanced samplings. (PubMed, Phys Chem Chem Phys)
Finally, analyses implied Duvelisib and Eganelisib as promising dual-purposed anti-COVID and anticancer drugs, potentially targeting Mpro and PI3Kγ to stop virus replication and cytokine storms concomitantly. We also distinguished hotspot residues imparting significant interactions.
Journal
|
PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma)
|
Copiktra (duvelisib) • eganelisib (IPI-549)
7d
Pediatric Patients Aged 4 to 11 Years With APDS (clinicaltrials.gov)
P3, N=15, Active, not recruiting, Pharming Technologies B.V. | Recruiting --> Active, not recruiting
Enrollment closed
|
CD20 (Membrane Spanning 4-Domains A1) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
|
CD20 positive
7d
New P2 trial • Combination therapy
|
BCL2 (B-cell CLL/lymphoma 2)
|
Venclexta (venetoclax) • Gazyva (obinutuzumab) • Itari (linperlisib)
10d
Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas. (PubMed, Br J Haematol)
The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.
Journal
|
PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
|
Brukinsa (zanubrutinib) • zandelisib (ME-401)
16d
Testing the Addition of Copanlisib to Usual Treatment (Fulvestrant and Abemaciclib) in Metastatic Breast Cancer (clinicaltrials.gov)
P1/2, N=24, Active, not recruiting, National Cancer Institute (NCI) | N=204 --> 24 | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Jun 2023
Enrollment change • Trial completion date • Trial primary 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
|
Prosigna™ Breast Cancer Prognostic Gene Signature Assay
|
Verzenio (abemaciclib) • fulvestrant • Aliqopa (copanlisib)
16d
Study of INCB040093 in Subjects With Previously Treated B-Cell Malignancies (clinicaltrials.gov)
P1, N=121, Active, not recruiting, Incyte Corporation | Trial completion date: Feb 2024 --> Aug 2024 | Trial primary completion date: Feb 2024 --> Aug 2024
Trial completion date • Trial primary completion date
|
itacitinib (INCB039110) • dezapelisib (INCB040093)
16d
Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy (clinicaltrials.gov)
P1, N=43, Recruiting, Washington University School of Medicine | Trial completion date: Oct 2029 --> May 2030 | Trial primary completion date: May 2025 --> Dec 2025
Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
Copiktra (duvelisib)
17d
Enrollment closed • Trial primary completion date • Combination therapy
|
Gazyva (obinutuzumab) • Aliqopa (copanlisib)
24d
Efficacy and Safety of Tenalisib in Patients With Metastatic Triple Negative Breast Cancer (TNBC) (clinicaltrials.gov)
P2, N=40, Recruiting, Rhizen Pharmaceuticals SA | Not yet recruiting --> Recruiting
Enrollment open • Metastases
|
tenalisib (RP6530)
25d
Glucose Metabolism in Acute Myeloid Leukemia Cell Line Is Regulated via Combinational PI3K/AKT/mTOR Pathway Inhibitors. (PubMed, Iran J Pharm Res)
HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination. A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.
Preclinical • Journal
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • HK2 (Hexokinase 2) • PKM (Pyruvate Kinase M1/2)
|
everolimus • Zydelig (idelalisib) • MK-2206
27d
Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas (clinicaltrials.gov)
P1, N=53, Active, not recruiting, Hutchmed | Trial completion date: Aug 2023 --> Dec 2024 | Trial primary completion date: Aug 2023 --> Jul 2024
Trial completion date • Trial primary completion date
|
amdizalisib (HMPL-689)
30d
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)
30d
Pembrolizumab + Idelalisib for Lung Cancer Study (clinicaltrials.gov)
P1/2, N=4, Terminated, Asha Nayak | N=40 --> 4 | Unknown status --> Terminated; The study was terminated due to poor accrual.
Enrollment change • Trial termination • Checkpoint inhibition
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
|
EGFR mutation • ALK mutation • ALK translocation
|
Keytruda (pembrolizumab) • Zydelig (idelalisib)
30d
Phase classification
|
Rituxan (rituximab) • lenalidomide • doxorubicin hydrochloride • cyclophosphamide • parsaclisib (INCB50465) • Monjuvi (tafasitamab-cxix)
1m
Evaluation of the cardiac safety of parsaclisib, a selective PI3Kδ inhibitor, in patients with previously treated B-cell malignancies: Results from the CITADEL-101 study. (PubMed, Pharmacol Res Perspect)
From the concentration-ΔQTcF analyses, the predicted ΔQTcF (90% CI) for all dose levels was between 0.365 (-1.75 to 2.48) and 7.87 ms (0.921-14.8), with the highest upper limit of CIs well below 20 ms, and therefore, a large QT/QTc effect was ruled out up to the highest dose level (45 mg) investigated. Overall, parsaclisib at the dose ranges studied did not reveal concentration-dependent effects on change in QTcF and did not have a significant effect on HR or cardiac conduction.
Journal
|
PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
|
parsaclisib (INCB50465)
1m
BR-101801-CT-101: BR101801 in Adult Patients With Advanced Hematologic Malignancies( Phase I) (clinicaltrials.gov)
P1, N=30, Active, not recruiting, Boryung Pharmaceutical Co., Ltd | Recruiting --> Active, not recruiting
Enrollment closed
|
BR101801
1m
PI3Kδ inhibition alleviates the brain injury during cerebral ischemia reperfusion via suppressing pericyte contraction in a TNF-α dependent manner. (PubMed, Exp Neurol)
CAL-101 suppressed the TNF-α-induced TRPV2 expression in OGD/R-treated PCs, thus inhibiting the Ca2+ uptake and PC contraction. Collectively, this study suggests that PI3Kδ is a critical regulator of PC function during ischemic stroke.
Journal
|
TNFA (Tumor Necrosis Factor-Alpha) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • TRPV2 (Transient Receptor Potential Cation Channel Subfamily V Member 2)
|
Zydelig (idelalisib)
1m
Intermittent Duvelisib Dosing in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov)
P2, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024
Trial completion date • Trial primary completion date
|
BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • FCER2 (Fc Fragment Of IgE Receptor II)
|
Chr t(11;14) • CCND1 overexpression
|
Copiktra (duvelisib) • ETP-47187
1m
A Study of INCB050465 in Subjects With Relapsed or Refractory Marginal Zone Lymphoma (CITADEL-204) (clinicaltrials.gov)
P2, N=110, Active, not recruiting, Incyte Corporation | Trial completion date: Dec 2023 --> May 2024
Trial completion date
|
parsaclisib (INCB50465)
1m
PI3K Delta Inhibitor in Relapsed / Refractory Autoimmune Hemolytic Anemia Patients After Receiving Two or More Lines of Therapy (clinicaltrials.gov)
P1, N=4, Terminated, Institute of Hematology & Blood Diseases Hospital, China | N=20 --> 4 | Trial completion date: Dec 2024 --> Feb 2024 | Recruiting --> Terminated; Did not meet the anticipated outcome.
Enrollment change • Trial completion date • Trial termination
|
Itari (linperlisib)
1m
Design, synthesis, molecular docking, and in vitro studies of 2-mercaptoquinazolin-4(3H)-ones as potential anti-breast cancer agents. (PubMed, Saudi Pharm J)
This study investigated the potential anticancer activity of some novel quinazolinone derivatives that were designed on the structural framework of two approved anticancer drugs, Ispinesib (KSP inhibitor) and Idelalisib (PI3Kδ inhibitor), to find out solutions for TNBC. The relative gene expression of pro-apoptotic and anti-apoptotic genes revealed an overexpression of the P53 and BAX genes and a downregulation of the BCL-2 gene by real-time PCR. So, this work proved that compounds 3a, 3b, and 3e could be developed as anticancer candidates, via their P53-dependent apoptotic activity.
Preclinical • Journal • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • BCL2 (B-cell CLL/lymphoma 2) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • BAX (BCL2-associated X protein) • ANXA5 (Annexin A5)
|
HER-2 expression • BAX expression
|
Zydelig (idelalisib) • ispinesib (SB-715992)
1m
Design, synthesis, molecular modelling and biological evaluation of novel 6-amino-5-cyano-2-thiopyrimidine derivatives as potent anticancer agents against leukemia and apoptotic inducers. (PubMed, J Enzyme Inhib Med Chem)
Molecular analysis of Duvelisib and compound 1c in PI3K was performed. Finally, these results suggest that 2-thiopyrimidine derivative 1c might serve as a model for designing novel anticancer drugs in the future.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • CASP3 (Caspase 3)
|
Copiktra (duvelisib)
2ms
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)
2ms
Integrating cfDNA liquid biopsy and organoid-based drug screening reveals PI3K signaling as a promising therapeutic target in colorectal cancer. (PubMed, J Transl Med)
Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.
Preclinical • Journal • Liquid biopsy • Biopsy
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • SMAD4 (SMAD family member 4) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
|
TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • SMAD4 mutation
|
everolimus • Piqray (alpelisib) • Zydelig (idelalisib)
2ms
Trial completion
|
Copiktra (duvelisib)
2ms
Phase 2 study of add-on parsaclisib in myelofibrosis patients with suboptimal response to ruxolitinib: Final results. (PubMed, Blood Adv)
Hemoglobin levels remained steady. The addition of parsaclisib to stable dose ruxolitinib can reduce splenomegaly and improve symptoms, with manageable toxicity in patients with myelofibrosis with suboptimal response to ruxolitinib.
P2 data • Journal
|
PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
|
Jakafi (ruxolitinib) • parsaclisib (INCB50465)
2ms
Combination of Pembrolizumab With TGR-1202 in Patients With Relapsed/Refractory CLL and B-cell NHL (clinicaltrials.gov)
P1, N=20, Active, not recruiting, University of Chicago | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2027
Trial completion date • Trial primary completion date
|
Keytruda (pembrolizumab) • Ukoniq (umbralisib)
2ms
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)
2ms
Efficacy and Safety of Linperlisib in Relapsed/Refractory Large Granular T Lymphocytic Leukemia (clinicaltrials.gov)
P2, N=41, Recruiting, Institute of Hematology & Blood Diseases Hospital, China
New P2 trial
|
Itari (linperlisib)
2ms
New P1/2 trial • Combination therapy
|
Aliqopa (copanlisib) • Firmagon (degarelix)
2ms
Acalabrutinib (ACP-196) in Combination With ACP-319, for Treatment of B-Cell Malignancies (clinicaltrials.gov)
P1/2, N=40, Active, not recruiting, Acerta Pharma BV | Trial completion date: Dec 2025 --> Apr 2026
Trial completion date • Combination therapy
|
Calquence (acalabrutinib) • ACP-319
2ms
KLRG1 Cell Depletion As A Novel Therapeutic Strategy In Patients With Mature T-cell lymphoma Subtypes. (PubMed, Clin Cancer Res)
Our findings suggest the potential benefit of a broader treatment strategy combining therapeutic antibodies with PI3Ki for the treatment of patients with mature T-cell and NK-cell neoplasms.
Journal
|
CD8 (cluster of differentiation 8) • NCAM1 (Neural cell adhesion molecule 1) • KLRG1 (Killer Cell Lectin Like Receptor G1) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)
|
KLRG1 expression
|
Copiktra (duvelisib)
2ms
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)
2ms
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)
3ms
PI3Kδ Inhibition Potentiates Glucocorticoids in B-lymphoblastic Leukemia by Decreasing Receptor Phosphorylation and Enhancing Gene Regulation. (PubMed, Cancers (Basel))
This mechanism and the response of patient specimens suggest that idelalisib will benefit most patients with B-ALL, but particularly patients with less responsive, including high-risk, disease. This combination is also promising for the development of less toxic glucocorticoid-sparing therapies.
Journal
|
PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • MAPK1 (Mitogen-activated protein kinase 1)
|
Zydelig (idelalisib)
3ms
A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL (clinicaltrials.gov)
P1, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2023 --> Mar 2024
Trial completion date • Combination therapy
|
Imbruvica (ibrutinib) • Ukoniq (umbralisib)
3ms
BR101801 enhances the radiosensitivity of p53-deficient colorectal cancer cells by inducing G2/M arrest, apoptosis, and senescence in a p53-independent manner. (PubMed, Am J Cancer Res)
Moreover, BR101801 exerted robust synergistic effects on IR-induced cell cycle arrest, apoptosis, and tumor growth inhibition, even in radioresistant HCT116 p53 cells. Overall, these findings provide a scientific rationale for combining BR101801 with IR as a new therapeutic strategy to overcome radioresistance induced by p53 deficiency.
Journal
|
PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma)
|
BR101801
3ms
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)
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 | 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)
3ms
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)