taselisib (GDC-0032) / Roche - LARVOL DELTA

Mechanisms of Acquired Resistance to PI3K Inhibitors in Breast Cancer: The Central Role of Autophagy (SABCS 2025) - "Taken together, our findings suggest that autophagy activation serves as a key adaptive mechanism driving acquired resistance to PI3K inhibitors such as taselisib in breast cancer. Targeting autophagy-related pathways may represent a promising therapeutic strategy to overcome or delay resistance and enhance the clinical efficacy of PI3K-targeted treatments."

Preclinical • Breast Cancer • Oncology • Solid Tumor • ATG5 • BECN1 • PIK3CA • PTEN • SQSTM1

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."

Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PIK3CA • PIK3CB • PIK3CD • PIK3CG

Body mass index (BMI) in postmenopausal patients (pts) with estrogen receptor (ER)-positive, HER2-negative early breast cancer (eBC): An exploratory analysis of LORELEI (ESMO 2025) - P2 | "The addition of taselisib appeared to mitigate this effect. In pts with obesity treated with letrozole + placebo, higher levels of pS6, a downstream Effector of the PI3K pathway, were associated with higher ORR."

Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • IL6

PIK3CA helical but not kinase mutations and enrichment of M2 macrophages predict response to taselisib in the LORELEI phase II randomized trial (ESMO 2025) - P2 | "Table: 116MO ORR taselisib (%) ORR placebo (%) Odd ratio, CI95% P-value univariate P-value multivariate Helical domain PIK3CA- mutants All (68/159, 43%) 69% 33% 4.7 (1.8-12.5) < 0.01 < 0.01 E542K 83% 10% 34 (2.7-2119) < 0.01 0.02 E545K 59% 44% 1.86 (0.52-6.61) 0.34 - Kinase domain PIK3CA-mutants All (58/159, 36%) 47% 43% 1.2 (0.5-2.9) 0.98 - H1047R 42% 43% 0.98 (0.35-7.77) 0.94 - Invasive lobular breast cancers All (80/334, 24%) 63% 47% 1.9 (0.8-4.6) 0.21 - PIK3CA- mutants 64% 48% 1.72 (0.4-6.9) 0.54 - PIK3CA wild-type 62% 47% 1.82 (0.4-8.7) 0.50 - Breast cancer of NST All (209/334, 63%) 46% 38% 1.4 (0.8-2.4) 0.22 - PIK3CA- mutant 51% 34% 2.0 (0.9-4.8) 0.08 - PIK3CA wild-type (116/334, 35%) 42% 41% (0.5-2.2) 0.93 - Conclusions PIK3CA HDmt but not KDmt predict response to taselisib in early-stage ER+/HER2- BCs. In ILC, macrophage polarization and T cell reinvigoration may contribute to taselisib efficacy."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD8 • CX3CR1 • ER • HER-2 • PIK3CA

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 | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Biomarker • Trial completion date • Trial primary completion date • Bladder Cancer • Brain Cancer • Breast Cancer • Cervical Cancer • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Hematological Malignancies • Hormone Receptor Positive Breast Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Refractory Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Thyroid Gland Carcinoma • Uterine Cancer • CD4 • MSI

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 • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

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."

Heterogeneity • IO biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • CD8 • EGR1 • GDF15 • RSPO3 • TGFBR2

Unlocking therapeutic potential of rigosertib as a selective therapy for ovarian cancer (AACR 2025) - "Subsequent combination drug screening revealed a cooperative effect between rigosertib and PI3K inhibitor (taselisib), suggesting that combining rigosertib with taselisib which restricts mTOR activation enhances therapeutic efficacy. This combination showed synergy across ovarian cancer cell lines, organoids, and xenograft models, with xenograft studies showing a significant reduction in tumor burden. These findings highlight the potential of rigosertib, especially when paired with PI3K inhibitors, to target the unique mutational landscape of ovarian cancer, offering a promising direction for more effective treatments."

Oncology • Ovarian Cancer • Solid Tumor

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 | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Breast Cancer • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • PIK3CA

Distinct dysregulated pathways in sporadic and Lynch syndrome-associated colorectal cancer offer insights for targeted treatment. (PubMed, FEBS Lett) - "Moreover, our findings highlight the therapeutic potential of PI3K-Akt pathway inhibitors, such as taselisib, for LS-associated CRC patients with high pathway dependency. Similarly, Wnt signalling pathway inhibitors, such as XAV939, offer a promising therapeutic approach for sporadic CRC. These findings underscore the importance of understanding the biological basis of disease for developing targeted therapies tailored to CRC subtype-specific oncogenic pathways."

Journal • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor

PIPA: Combination of PI3 Kinase Inhibitors and PAlbociclib (clinicaltrials.gov) - P1 | N=79 | Completed | Sponsor: Royal Marsden NHS Foundation Trust | Unknown status ➔ Completed

Combination therapy • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1S1 • ER • GSK3B • HER-2 • KRAS • PIK3CA • PTH2R

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 | Sponsor: Otto Metzger, MD | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

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 | Sponsor: 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.

Combination therapy • Metastases • Phase classification • Trial termination • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • HER-2 • PIK3CA

Rational Design of Targeted Gold Nanoclusters with High Affinity to Integrin αvβ3 for Combination Cancer Therapy. (PubMed, Bioconjug Chem) - "The AuNCs were functionalized with anticancer drugs (5-fluorouracil or signaling pathways inhibitors, such as capivasertib, linifanib, tanespimycin, and taselisib) and integrin-targeting peptides (RGD4C or QS13), and we identified the optimal mixed ligand layer to enhance their binding affinity to the cancer cell receptor. Our simulations also revealed that Mn2+ cations are crucial for stabilizing the αvβ3-AuNC complex. These findings demonstrate the potential of carefully designing the surface composition of TNDDSs to optimize their target affinity and specificity."

Journal • Oncology

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) - P1/2, P3 | "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."

Combination therapy • Journal • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

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 • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Oncology • Rheumatology • Seronegative Spondyloarthropathies • IL17A • MTA1

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."

Combination therapy • Journal • Metastases • P1 data • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Positive Breast Cancer • Mucositis • Oncology • Solid Tumor • Stomatitis • PIK3CA

PIK3CA mutation and response to neoadjuvant taselisib and endocrine therapy: A biomarker study of the LORELEI trial (ESMO-BC 2024) - P2 | "Non-responders with PIK3CA MT tumors showed enrichment of immune related signaling in the taselisib arm. Further analyses will be presented."

Biomarker • Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

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 | Sponsor: National Cancer Institute (NCI)

Trial completion date • Breast Cancer • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • PIK3CA

Kinome expression profiling improves risk stratification and therapeutic targeting in myelodysplastic syndromes. (PubMed, Blood Adv) - "By investigating the Genomics of Drug Sensitivity in Cancer (GDSC) database, we identified axitinib and taselisib as candidate compounds that could potentially target the KISS-high myeloblasts. Altogether, our findings suggest that KISS holds the potential to improve the current prognostic scheme of MDS and inform novel therapeutic opportunities."

Journal • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ASXL1 • MAST4 • NPM1 • NTRK1 • PAK6 • PTK7 • RUNX1 • STAG2 • TP53

Machine learning-based disulfidptosis-related lncRNA signature predicts prognosis, immune infiltration and drug sensitivity in hepatocellular carcinoma. (PubMed, Sci Rep) - "Additionally, the high-risk group exhibited higher sensitivity to Afatinib, Fulvestrant, Gefitinib, Osimertinib, Sapitinib, and Taselisib. In conclusion, our study highlighted the potential utility of the constructed DRLPS in the prognosis prediction of HCC patients, which demonstrated promising clinical application value."

IO biomarker • Journal • Machine learning • Cognitive Disorders • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • ZNF23

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 | Active, not recruiting | Sponsor: Otto Metzger, MD | Trial completion date: Dec 2023 ➔ May 2024

Combination therapy • Metastases • Trial completion date • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

A comprehensive review of small molecules targeting PI3K pathway: Exploring the structural development for the treatment of breast cancer. (PubMed, Bioorg Chem) - "Various heterocyclic small molecules are undergoing clinical trials, such as Alpelisib, the first orally available FDA-approved drug targeting PI3K; others include buparlisib, pictilisib, and taselisib, which inhibit class I PI3K. These drugs are used for the treatment of breast cancer but still have various side effects with their high cost. Therefore, the primary goal of this review is to include all current advances in the development of anticancer medicines that target PI3K over-activation in the treatment of breast cancer."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Multi-omics approaches establishing histone modification based prognostic model in glioma patients and further verification of the carcinogenesis mechanism. (PubMed, Funct Integr Genomics) - "5-Fluorouracil_1073 and Taselisib_1561 were predicted as potential treatment options for GBM patients, while ABT737_1910 and Wnt_C59-1622 exhibited superior response in GBM patients of the HR group. We presented a novel prognostic model for patients with GBM, based on histone modification-related genes. In addition, we identified the crucial role of the TMEM176A in the regulation of GBM carcinogenic phenotypes for the first time."

Epigenetic controller • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • AEBP1 • CD8 • CD81 • TGFB1 • TP53

Transcriptome data-based status of PI3K/AKT/mTOR pathway indicates heterogeneity and immune modulation in patients with pancreatic ductal adenocarcinoma. (PubMed, J Gene Med) - "These findings suggest that targeting the PI3K/AKT/mTOR pathway may have therapeutic potential in PDAC, and distinct pathway states, immune modulation and tumor microenvironments have prognostic value."

Heterogeneity • Journal • Gastrointestinal Cancer • Immune Modulation • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD8