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    DRUG:

    taselisib (GDC-0032)

    i
    Other names: GDC-0032, RG7604, RO5537381
    Company:
    Roche
    Drug class:
    PI3Kα inhibitor
    Related drugs:
    27d
    PI3K inhibitors: Efficacy in diverse cancer forms. (PubMed, Cancer Treat Res Commun)
    The PI3K inhibitors GDC-0032 and INK1117 for PI3K-α and AZD8186 for PI3K-β are now being studied in clinical trials. Research on the clinical development, therapeutic utility, and structural insights of new PI3K inhibitors is the main emphasis of this review. The inhibitors have been shown promising anticancer activity relationships.
    Review • Journal
    |
    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) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    taselisib (GDC-0032) • AZD8186 • serabelisib (MLN1117)
    2ms
    NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov)
    P2, N=6452, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    MSI (Microsatellite instability) • CD4 (CD4 Molecule)
    |
    Opdivo (nivolumab) • Herceptin (trastuzumab) • Mekinist (trametinib) • Xalkori (crizotinib) • Tagrisso (osimertinib) • Gilotrif (afatinib) • Ibrance (palbociclib) • dasatinib • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • sunitinib • Kadcyla (ado-trastuzumab emtansine) • Balversa (erdafitinib) • Mektovi (binimetinib) • adavosertib (AZD1775) • Truqap (capivasertib) • Aliqopa (copanlisib) • fexagratinib (ABSK091) • sapanisertib (CB-228) • ipatasertib (RG7440) • taselisib (GDC-0032) • omipalisib (GSK2126458) • ulixertinib (BVD-523) • Erivedge (vismodegib) • Trazimera (trastuzumab-qyyp) • Fakzynja (defactinib) • GSK2636771 • Paletan (pertuzumab biosimilar) • relatlimab (BMS-986016) • ABP 206 (nivolumab biosimilar) • Pertuvia (pertuzumab biosimilar)
    5ms
    Disease Modeling and External Model Evaluation Through Clinical Data Sharing Platform for HR+/HER2- Breast Cancer. (PubMed, CPT Pharmacometrics Syst Pharmacol)
    The CONFIRM study (Phase 3 study comparing fulvestrant 250 vs. 500 mg) was used for model development, and the PALOMA-3 and SANDPIPER Phase 3 studies (palbociclib and taselisib) were used for external model qualifications. The TGI-OS model showed large underestimation for the OS for PALOMA-3; nevertheless, the predicted treatment effect (hazard ratio of OS) was in good agreement with the observation for both studies, suggesting its potential as a tool to support drug development decisions. While integrating shared clinical trial data from multiple sources, facilitated by platforms like Vivli, is crucial for advancing predictive modeling efforts, caution should be exercised when such models are applied for new studies, especially when there are breakthroughs in the treatment landscape.
    Clinical data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HR positive • HER-2 negative
    |
    Ibrance (palbociclib) • fulvestrant • taselisib (GDC-0032)
    7ms
    Deciphering of intra-tumoural heterogeneity and the interplay between metastasis-associated meta-program and myofibroblasts in gastric cancer. (PubMed, Clin Transl Med)
    Seven robust meta-programs (MP1-MP7) were identified in gastric cancer. MP7 was strongly correlated with cancer metastasis and poor survival of gastric cancer patients. MP7 promoted fibroblast transformation into myCAFs via GDF15/TGFBR2, creating an immune lockdown microenvironment. MyCAFs induced MP7 transformation via the RSPO3/EGR1 pathway, promoting gastric cancer cell migration. Taselisib and Lapatinib were potent inhibitors of MP7 GC cells.
    Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • GDF15 (Growth differentiation factor 15) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • RSPO3 (R-Spondin 3) • EGR1 (Early Growth Response 1)
    |
    lapatinib • taselisib (GDC-0032)
    8ms
    EAY131-I: Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I) (clinicaltrials.gov)
    P2, N=70, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026
    Trial completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    taselisib (GDC-0032)
    1year
    Phase Ib Dose-escalation Trial of Taselisib (GDC-0032) in Combination With Anti-HER2 Therapies in Participants With Advanced HER2+ Breast Cancer (clinicaltrials.gov)
    P1, N=68, Completed, Otto Metzger, MD | Active, not recruiting --> Completed
    Trial completion
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    Herceptin (trastuzumab) • paclitaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • taselisib (GDC-0032)
    1year
    PIPA: Combination of PI3 Kinase Inhibitors and PAlbociclib (clinicaltrials.gov)
    P1, N=79, Completed, Royal Marsden NHS Foundation Trust | Unknown status --> Completed
    Trial completion • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • GSK3B (Glycogen Synthase Kinase 3 Beta) • PTH2R (Parathyroid Hormone 2 Receptor) • AKT1S1 (AKT1 Substrate 1)
    |
    KRAS mutation • PIK3CA mutation
    |
    Ibrance (palbociclib) • fulvestrant • pictilisib (GDC-0941) • taselisib (GDC-0032)
    over1year
    A Dose Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Participants With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma (NHL) and in Combination With Endocrine Therapy in Locally Advanced or Metastatic Hormone Receptor-Positive Breast Cancer (clinicaltrials.gov)
    P1, N=674, Terminated, Genentech, Inc. | Phase classification: P1/2 --> P1 | Completed --> Terminated; The Sponsor discontinued the manufacturing and development of taselisib due to modest clinical benefit and limited tolerability.
    Phase classification • Trial termination • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    fulvestrant • letrozole • taselisib (GDC-0032)
    over1year
    Quantitative characterization of the effects of fulvestrant alone or in combination with taselisib (PI3Kinase inhibitor) on longitudinal tumor growth in patients with estrogen receptor-positive, HER2-negative, PIK3CA-mutant, advanced or metastatic breast cancer. (PubMed, Cancer Chemother Pharmacol)
    These results have important implications for understanding the therapeutic impact of combination treatment approaches and individualized responses to these treatments. Finally, this work, emphasizes the importance of model informed drug development for targeted cancer therapy.
    Journal • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    fulvestrant • taselisib (GDC-0032)
    over1year
    Sex dimorphism of IL-17-secreting peripheral blood mononuclear cells in ankylosing spondylitis based on bioinformatics analysis and machine learning. (PubMed, BMC Musculoskelet Disord)
    We analyzed the sex dimorphism of IL-17-secreting PBMCs in AS. The results showed that mast cell activation was stronger in males, while the expression of TNF was higher in females. In addition, through machine learning and the CMAP database, we found that genes such as METRN and TMC4 may promote the development of AS, and drugs such as atorvastatin potentially could be used for AS treatment.
    Journal • Machine learning
    |
    IL17A (Interleukin 17A)
    |
    taselisib (GDC-0032)
    over1year
    Phase Ib dose-escalation trial of taselisib (GDC-0032) in combination with HER2-directed therapies in patients with advanced HER2+ breast cancer. (PubMed, ESMO Open)
    PIK3CA targeting with taselisib in combination with HER2-targeted therapies was associated with both promising efficacy and substantial toxicities.
    P1 data • Journal • Combination therapy • Metastases
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    paclitaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • fulvestrant • taselisib (GDC-0032)
    over1year
    Testing GDC-0032 (Taselisib) as a Potential Targeted Treatment in Cancers With PIK3CA Genetic Changes (MATCH-Subprotocol I) (clinicaltrials.gov)
    P2, N=70, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation
    |
    taselisib (GDC-0032)