taselisib (GDC-0032) / Roche - LARVOL DELTA

PI3K inhibition in combination with tamoxifen in patients with metastatic HR+/HER2- breast cancer: clinical and circulating tumor DNA results. (PubMed, Clin Cancer Res) - "Our findings suggest efficacy of PI3K inhibition + tamoxifen beyond second-line treatment and after prior targeted therapies, including CDK4/6 inhibition in metastatic HR+/HER2- breast cancer although the magnitude of benefit did not outweigh the tolerability of this combination. Exploratory biomarker analysis indicates that tumor fraction determined in ctDNA differentiates patients based on prognosis and may help to optimize patient selection for targeted treatment strategies."

Circulating tumor DNA • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

Advances in the Targeted Therapy for PIK3CA-Related Overgrowth Spectrum (PROS): From Molecular Mechanisms to Clinical Translation. (PubMed, Pediatr Blood Cancer) - "Other agents, including taselisib and miransertib, have shown limited clinical benefits, and their further development has been constrained by safety concerns and insufficient efficacy. Although mTOR inhibitors, such as sirolimus, have shown partial efficacy in symptom control, durable responses remain uncommon, and recurrence after treatment discontinuation has been observed. Long-term safety, particularly in pediatric populations, remains to be fully established. In conclusion, targeted therapies, particularly alpelisib, represent a significant advancement in the management of PROS, although optimization of patient selection, long-term risk assessment, and strategies to minimize recurrence remain important unmet needs."

Journal • Review • Pediatrics • PIK3CA

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 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

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

Body mass index in postmenopausal women with estrogen receptor-positive, HER2-negative early breast cancer: An exploratory analysis of the LORELEI trial. (PubMed, Eur J Cancer) - P2 | "Obesity was associated with lower ORR with letrozole alone, whereas this association was not observed in patients treated with taselisib."

Journal • Breast Cancer • Diabetes • Estrogen Receptor Positive Breast Cancer • Genetic Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Obesity • Oncology • Solid Tumor • ER • HER-2 • IL6

Taselisib, a PI3K inhibitor, alleviates neuropathic pain through HIF-1a-mediated angiogenesis in a rat model of chronic constriction injury. (PubMed, Neuroimmunomodulation) - "Taselisib alleviates neuropathic pain by disrupting HIF-1α-mediated angiogenic, inflammatory, and metabolic signaling. Targeting the PI3K-HIF-1α axis offers a promising therapeutic approach."

Journal • Preclinical • Inflammation • Metabolic Disorders • Neuralgia • Pain • HIF1A • IL1B • IL6 • PFKM • RELA • SLC2A1

Integrative multi-omics and machine learning reveal PLAUR as a Pan-Cancer prognostic biomarker and potential therapeutic target. (PubMed, Bioorg Chem) - "We identified four FDA-approved drugs (5-Fluorouracil, Irinotecan, Talazoparib, Gemcitabine) that may have potential binding affinity to PLAUR through in silico analyses, and in vitro functional assays using the human tongue squamous cell carcinoma cell line CAL-27. Furthermore, we characterized peroxidasin (PXDN) as a core PLAUR-interacting hub and propose five candidate drugs (IGF1R-3801, Taselisib, Dasatinib, 5-Fluorouracil, and Alpelisib) for a synergistic dual-target strategy. Our work establishes PLAUR as a pivotal pan-cancer biomarker and potential therapeutic target, providing a rational framework for precision oncology."

Biomarker • Journal • Pan tumor • Oncology • Squamous Cell Carcinoma • Tongue Carcinoma • PLAUR

Integrated analysis of programmed cell death-related genes identifies CORO1A as an apoptosis-associated gene in acute myeloid leukemia. (PubMed, PeerJ) - "OncoPredict suggested higher sensitivity in the high-risk group to 5-fluorouracil, PI3K-AKT-mTOR inhibitors (afuresertib, pictilisib, taselisib, dactolisib), and the MET inhibitor savolitinib. Multi-omic integration of PCD-related genes delineates PCD-driven heterogeneity in AML and yields a robust five-gene prognostic model with therapeutic implications. CORO1A emerges as a potential apoptosis-associated oncogene that promoting AML cell survival."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • BCL2 • CD31 • CORO • CXCR3 • IL10 • ITGA4 • PECAM1 • PPBP

Comparative risk of hyperglycemia with PI3K, AKT, and mTOR inhibitors in breast cancer: A systematic review and meta-analysis (ESMO-BC 2026) - "Alpelisib demonstrated the highest risk of hyperglycemia (any-grade RR 6.90, 95% CI 5.01–9.51; grade ≥3 RR 58.75, 95% CI 16.96–203.49). Inavolisib was also associated with increased risk (any-grade RR 4.69, 95% CI 3.13–7.04; grade ≥3 RR 23.28, 95% CI 1.38–391.84; single trial). Capivasertib and taselisib showed intermediate risk (capivasertib: any-grade RR 3.53, 95% CI 2.42–5.16; grade ≥3 RR 10.02, 95% CI 2.70–37.16; taselisib: any-grade RR 3.19, 95% CI 1.64–6.21; grade ≥3 RR 14.61, 95% CI 2.79–76.38). Everolimus demonstrated the lowest relative risk (any-grade RR 2.19, 95% CI 1.80–2.68), with grade ≥3 hyperglycemia not reaching statistical significance (RR 5.89, 95% CI 0.74–47.13). All PAM pathway inhibitors were associated with an increased risk of hyperglycemia compared with control regimens, with clear stratification by drug class. All PAM pathway inhibitors were associated with an increased risk of hyperglycemia compared with control regimens, with clear..."

Retrospective data • Review • Breast Cancer • Oncology • Solid Tumor • IR • PIK3CA

A tumor microenvironment-focused signature based on m6A and lactylation modification predicts prognosis and immunotherapy response in hepatocellular carcinoma. (PubMed, Discov Oncol) - "Specifically, the high-risk group exhibited increased immune cell infiltration, lower IC50 values for several drugs including 5-fluorouracil, afatinib, crizotinib, cediranib, taselisib, and staurosporine; Whereas the low-risk group displayed reduced stromal component proportions and better responses to entinostat, irinotecan, KRAS inhibitors, cisplatin, axitinib, and topotecan. The lactylation-m6A related prognostic model exhibited robust predictive efficiency in HCC. TCOF1 and HDAC1 may be promising tumor biomarkers for HCC and more researches are needed to validate these results."

Biomarker • IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • HDAC1 • KRAS

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 2026 ➔ Mar 2027

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

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

FAM64A Potentiates Bladder Carcinoma Tumorigenesis and Metastasis Through PI3K/mTORC2/AKT Pathway Activation. (PubMed, Cancers (Basel)) - "Taselisib reversed FAM64A-induced EMT and malignant phenotypes. FAM64A drives BLCA progression via PI3K/mTORC2/AKT-mediated EMT, serving as a potential prognostic biomarker and therapeutic target for metastatic BLCA."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • AR • CCNB1 • SNAI2 • VIM

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

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

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