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    DRUG:

    inavolisib (GDC-0077)

    i
    Other names: GDC-0077, GDC 0077, GDC0077, RG6114, RG-6114, RG 6114, RO7113755, RO 7113755
    Company:
    Roche
    Drug class:
    PIK3CA inhibitor
    Related drugs:
    26d
    BOUQUET: A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors (clinicaltrials.gov)
    P2, N=550, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    ER (Estrogen receptor)
    |
    Avastin (bevacizumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • paclitaxel • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Verzenio (abemaciclib) • cyclophosphamide • letrozole • ipatasertib (RG7440) • triptorelin • goserelin acetate • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    2ms
    GO39374: To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer (clinicaltrials.gov)
    P1, N=256, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Herceptin (trastuzumab) • Ibrance (palbociclib) • Perjeta (pertuzumab) • fulvestrant • letrozole • metformin • inavolisib (GDC-0077)
    2ms
    MyTACTIC: A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response (clinicaltrials.gov)
    P2, N=252, Completed, Genentech, Inc. | Active, not recruiting --> Completed
    Trial completion • Tumor mutational burden • Metastases
    |
    Tecentriq (atezolizumab) • Rozlytrek (entrectinib) • paclitaxel • docetaxel • Alecensa (alectinib) • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • capecitabine • Gavreto (pralsetinib) • Tukysa (tucatinib) • ipatasertib (RG7440) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf) • tiragolumab (RG6058)
    2ms
    A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC) (clinicaltrials.gov)
    P1, N=422, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2026 --> Apr 2026
    Trial completion date • Metastases
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • divarasib (RG6330) • inavolisib (GDC-0077) • SY-5609 • tiragolumab (RG6058)
    3ms
    INAVO120: A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=325, Active, not recruiting, Hoffmann-La Roche | Phase classification: P2/3 --> P3
    Phase classification • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • fulvestrant • inavolisib (GDC-0077)
    3ms
    AFT-50 EndoMAP: A phase Ib/II multi-cohort study of targeted agents for patients with recurrent or persistent endometrial cancer (SGO 2024)
    Approximately, 30% of recurrent EC pts fall into this category. Pairing ICI with targeted therapies carries the potential to elicit prolonged anti-tumor effects. Atezolizumab (Atezo) is a humanized monoclonal PD-L1 inhibitor that has demonstrated monotherapy antitumor activity with an acceptable safety profile in relapsed recurrent EC...In cohort A, pts may be eligible for one of the following doublets: Atezo+ipatasertib (PIK3CA/PTEN/AKT1-altered cancers), Atezo+talazoparib (tumors with genomic loss of heterozygosity (LOH) ≥16%), Atezo+Trastuzumab emtansine (ERBB2/HER2 mutated and/or amplified tumors), and Atezo+Tiragolumab (MSI-H and/or TMB>10 mut/MB). The Atezo+bevacizumab (biomarker unmatched) arm is closed to enrollment...Pts will receive Atezo in addition to the targeted agent (at the study approved dosing schedule) until progression, unacceptable toxicity, pt or physician decision to withdraw from the study, death, or study termination. Pts in cohort B, will be eligible for inavolisib (PIK3CA/PTEN/AKT1-altered cancers) + letrozole. The primary endpoint for Cohort A is confirmed overall response rate (ORR) for each cohort, and for Cohort B is progression free survival at 6 months...As a platform study, additional arms may be added, as supported by evolving understanding of EC and molecular targets. EndoMAP is actively enrolling at 18 sites in the US with a target of 25 sites nationwide.
    P1/2 data • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    MSI-H/dMMR • HER-2 amplification • HER-2 mutation
    |
    FoundationOne® CDx
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • Kadcyla (ado-trastuzumab emtansine) • Talzenna (talazoparib) • letrozole • ipatasertib (RG7440) • inavolisib (GDC-0077) • tiragolumab (RG6058)
    4ms
    Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations (YIR 2024)
    Background: PIK3CA mutations occur in ~40% of HR-positive breast cancers, where alpelisib, an orthosteric PI3Kα inhibitor, is FDA-approved in combination with fulvestrant... To identify on-target and off-target alterations potentially mediating resistance to PI3Kα inhibitors, we used a targeted next-generation sequencing assay (Guardant360; Guardant Health) to analyze ctDNA in serially collected plasma samples from 32 patients with PIK3CA-mutated advanced HR-positive, HER2-negative breast cancer treated with alpelisib and inavolisib...Some mutations had differential effects on PI3Kaselective vs. pan-PI3K inhibitors, but resistance induced by all mutations could be overcome by the novel allosteric pan-mutant-selective PI3Ka-inhibitor RLY-2608... In one of the largest patient cohorts analyzed to date, this study defines the clinical landscape of acquired resistance to PI3Ka inhibitors. Genomic alterations within the PI3K pathway represent a major mode of resistance and identify a novel class of secondary PIK3CA resistance mutations that can be overcome by an allosteric PI3Ka inhibitor. Together, these findings provide insights to guide strategies to overcome resistance in PIK3CA-mutated cancers.
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    HR positive • HER-2 negative • PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • AKT1 mutation • PIK3CA E545 • PTEN mutation + HR positive
    |
    Guardant360® CDx
    |
    Piqray (alpelisib) • fulvestrant • RLY-2608 • inavolisib (GDC-0077)
    4ms
    INAVO120: A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P2/3, N=325, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • fulvestrant • inavolisib (GDC-0077)
    4ms
    MiRaDoR: A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population (clinicaltrials.gov)
    P2; Trial completion date: Mar 2028 --> Dec 2028 | Initiation date: Sep 2023 --> Dec 2023 | Trial primary completion date: Dec 2024 --> Dec 2028
    Trial completion date • Trial primary completion date • Trial initiation date • Minimal residual disease • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HR positive • HER-2 negative • PIK3CA mutation
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • MammaPrint • Oncotype DX Breast Recurrence Score®Test
    |
    Verzenio (abemaciclib) • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    6ms
    A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P2/3, N=325, Recruiting, Hoffmann-La Roche | Phase classification: P3 --> P2/3
    Phase classification • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • fulvestrant • inavolisib (GDC-0077)
    6ms
    A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation (clinicaltrials.gov)
    P1, N=498, Recruiting, Genentech, Inc. | Phase classification: P1a/1b --> P1
    Phase classification • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • erlotinib • divarasib (RG6330) • inavolisib (GDC-0077) • migoprotafib (RLY-1971)
    6ms
    INAVO122: a Phase III study of maintenance inavolisib or placebo + pertuzumab + trastuzumab following induction with pertuzumab + trastuzumab + a taxane in patients with PIK3CA-mutated, HER2-positive advanced breast cancer (SABCS 2023)
    The current study will assess the efficacy and safety of maintenance inavolisib + fixed-dose combination of pertuzumab + trastuzumab for subcutaneous injection (PH FDC SC) after first-line induction treatment in patients with PIK3CA-mutated, HER2+, advanced BC (aBC). ACCRUAL Target randomization is ~230 patients; recruitment began in July 2023. CONTACT INFORMATION For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only).
    Clinical • P3 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 positive • PIK3CA mutation
    |
    Perjeta (pertuzumab) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    6ms
    INAVO121: Phase III study of inavolisib + fulvestrant vs alpelisib + fulvestrant in patients with hormone receptor-positive, HER2-negative, PIK3CA‑mutated locally advanced or metastatic breast cancer (SABCS 2023)
    Clinicaltrials.gov number NCT05646862. This abstract was originally presented at ASCO 2023 (TPS1123).
    Clinical • P3 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative • PTEN mutation + HR positive
    |
    Piqray (alpelisib) • fulvestrant • inavolisib (GDC-0077)
    6ms
    Interim analysis of giredestrant + inavolisib in MORPHEUS Breast Cancer: a Phase Ib/II study of giredestrant treatment combinations in estrogen receptor-positive, HER2-negative, locally advanced/metastatic breast cancer (SABCS 2023)
    Prior fulvestrant (FUL) was received by 53% of patients in the GIR + INAVO arm (n = 8). Safety summary Data are % of patients. AE, adverse event; GIR, giredestrant; INAVO, inavolisib; TRAE, treatment-related adverse event; tx, treatment.
    P1/2 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    ER positive • HER-2 negative • PIK3CA mutation • ER positive + HER-2 negative • CDK4 mutation
    |
    FoundationOne® Liquid CDx
    |
    fulvestrant • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    6ms
    MiRaDor: A proof-of-concept study of treatment efficacy by monitoring Minimal Residual Disease (MRD) using circulating tumor DNA (ctDNA) in hormone receptor-positive/HER2-negative (HR+/HER2-) early breast cancer (EBC) (SABCS 2023)
    Selection criteria include pts: a) with HR+/HER2- EBC at high risk of relapse, b) on adjuvant treatment with endocrine therapy (ET) for at least 2 years with 3 additional years of planned ET, c) no prior treatment with cyclin-dependent kinases 4/6 inhibitors or fulvestrant, and d) had surgery for their primary BC in the last 5 years...Pts with positive ctDNA without radiological disease progression (PD) will be allocated to 1 of the treatment arms (n=10): A) standard ET; B) giredestrant; C) giredestrant + abemaciclib; or D) giredestrant + inavolisib (if PIK3CA mutation)...Key secondary objectives include the proportion of pts with 90% decrease in baseline ctDNA at 6, 9, and 12 months, 70%, and 50% decrease in ctDNA at 3, 6, 9, and 12 months, and treatment safety and tolerability. A cohort expansion up to 20 pts in 1 or 2 arms will occur if at 3 months a 90% ctDNA decrease is observed in at least 30% of pts and if, after 3 additional months, a 90% ctDNA decrease is maintained in at least 20% of pts.
    Clinical • Minimal residual disease • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative • PTEN mutation + HR positive
    |
    FoundationOne®Tracker
    |
    Verzenio (abemaciclib) • fulvestrant • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    6ms
    Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations (SABCS 2023)
    Background: PIK3CA mutations occur in ~40% of HR-positive breast cancers, where alpelisib, an orthosteric PI3Kα inhibitor, is FDA-approved in combination with fulvestrant... To identify on-target and off-target alterations potentially mediating resistance to PI3Kα inhibitors, we used a targeted next-generation sequencing assay (Guardant360; Guardant Health) to analyze ctDNA in serially collected plasma samples from 32 patients with PIK3CA-mutated advanced HR-positive, HER2-negative breast cancer treated with alpelisib and inavolisib...Some mutations had differential effects on PI3Ka-selective vs. pan-PI3K inhibitors, but resistance induced by all mutations could be overcome by the novel allosteric pan-mutant-selective PI3Ka-inhibitor RLY-2608... In one of the largest patient cohorts analyzed to date, this study defines the clinical landscape of acquired resistance to PI3Ka inhibitors. Genomic alterations within the PI3K pathway represent a major mode of resistance and identify a novel class of secondary PIK3CA resistance mutations that can be overcome by an allosteric PI3Ka inhibitor. Together, these findings provide insights to guide strategies to overcome resistance in PIK3CA-mutated cancers.
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    HR positive • HER-2 negative • PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • AKT1 mutation • PIK3CA E545 • PTEN mutation + HR positive
    |
    Guardant360® CDx
    |
    Piqray (alpelisib) • fulvestrant • RLY-2608 • inavolisib (GDC-0077)
    7ms
    A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=325, Recruiting, Hoffmann-La Roche | Trial primary completion date: Nov 2025 --> Sep 2023
    Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • fulvestrant • inavolisib (GDC-0077)
    7ms
    A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=325, Recruiting, Hoffmann-La Roche | Trial completion date: Nov 2025 --> Sep 2030 | Trial primary completion date: Sep 2023 --> Nov 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • fulvestrant • inavolisib (GDC-0077)
    8ms
    BOUQUET: A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors (clinicaltrials.gov)
    P2, N=550, Recruiting, Hoffmann-La Roche | Trial primary completion date: Dec 2026 --> May 2028
    Trial primary completion date
    |
    ER (Estrogen receptor)
    |
    Avastin (bevacizumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • paclitaxel • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Verzenio (abemaciclib) • cyclophosphamide • letrozole • ipatasertib (RG7440) • triptorelin • goserelin acetate • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    8ms
    Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov)
    P1/2; Active, not recruiting --> Recruiting
    Enrollment open • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PD-L1 expression • PIK3CA mutation
    |
    VENTANA PD-L1 (SP142) Assay
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Actemra IV (tocilizumab) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)
    10ms
    Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
    P2, N=240, Recruiting, German Cancer Research Center | Not yet recruiting --> Recruiting
    Enrollment open
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
    |
    Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    11ms
    A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=230, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 positive • PIK3CA mutation
    |
    tamoxifen • fulvestrant • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    11ms
    Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
    P2, N=240, Not yet recruiting, German Cancer Research Center | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Apr 2029 --> Mar 2030
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PALB2 mutation • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
    |
    Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    11ms
    A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=320, Recruiting, Hoffmann-La Roche | Trial primary completion date: Sep 2025 --> Sep 2023
    Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Ibrance (palbociclib) • fulvestrant • inavolisib (GDC-0077)
    11ms
    Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov)
    P1/2; N=133 --> 242 | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026
    Trial completion date • Trial primary completion date • Enrollment change • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PD-L1 expression • PIK3CA mutation
    |
    VENTANA PD-L1 (SP142) Assay
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Actemra IV (tocilizumab) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)
    11ms
    A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov)
    P3, N=230, Not yet recruiting, Hoffmann-La Roche
    New P3 trial • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 positive • PIK3CA mutation
    |
    tamoxifen • fulvestrant • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    12ms
    ENGOT-GYN2: A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors (clinicaltrials.gov)
    P2, N=550, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2026 --> Dec 2028 | Trial primary completion date: Aug 2024 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    ER (Estrogen receptor)
    |
    Avastin (bevacizumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • paclitaxel • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Verzenio (abemaciclib) • cyclophosphamide • letrozole • ipatasertib (RG7440) • triptorelin • goserelin acetate • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    12ms
    A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC) (clinicaltrials.gov)
    P1, N=340, Recruiting, Hoffmann-La Roche | Trial completion date: Jan 2026 --> Aug 2026
    Trial completion date • Metastases
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • divarasib (RG6330) • inavolisib (GDC-0077) • SY-5609 • tiragolumab (RG6058)
    1year
    INAVO121: Phase III study of inavolisib (INAVO) + fulvestrant (FUL) vs. alpelisib (ALP) + FUL in patients (pts) with hormone receptor-positive, HER2-negative (HR+, HER2–) PIK3CA‑mutated (mut) locally advanced or metastatic breast cancer (LA/mBC). (ASCO 2023)
    An independent data monitoring committee will be in place for safety and efficacy. Clinical trial information: NCT05646862.
    Clinical • P3 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative
    |
    Piqray (alpelisib) • fulvestrant • inavolisib (GDC-0077)
    1year
    AFT-50 EndoMAP: A phase IB/II multi-cohort study of targeted agents for patients with recurrent or persistent endometrial cancer. (ASCO 2023)
    In cohort A, pts may be eligible for one of the following doublets: Atezo+ipatasertib (PIK3CA/PTEN/AKT1-altered cancers), Atezo+talazoparib (tumors with genomic loss of heterozygosity (LOH) ≥16%), Atezo+Trastuzumab emtansine (ERBB2/HER2 mutated and/or amplified tumors), Atezo+Tiragolumab (MSI-H and/or TMB>10 mut/MB), and Atezo+bevacizumab (biomarker unmatched)...Pts in cohort B, will be eligible for inavolisib (PIK3CA/PTEN/AKT1-altered cancers) + letrozole...EndoMAP is actively enrolling at 17 sites in the US with a target of 25 sites nationwide. Clinical trial information: NCT04486352.
    P1/2 data • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    MSI-H/dMMR • HER-2 amplification • HER-2 mutation
    |
    FoundationOne® CDx
    |
    Avastin (bevacizumab) • Kadcyla (ado-trastuzumab emtansine) • Talzenna (talazoparib) • letrozole • ipatasertib (RG7440) • inavolisib (GDC-0077) • tiragolumab (RG6058)
    1year
    ENGOT-GYN2: A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors (clinicaltrials.gov)
    P2, N=550, Recruiting, Hoffmann-La Roche | N=400 --> 550 | Trial completion date: Mar 2026 --> Sep 2026
    Enrollment change • Trial completion date
    |
    ER (Estrogen receptor)
    |
    Avastin (bevacizumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • paclitaxel • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Verzenio (abemaciclib) • cyclophosphamide • letrozole • ipatasertib (RG7440) • triptorelin • goserelin acetate • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    1year
    Effective Combination Therapies for the Treatment of HER2 Cancer. (PubMed, ACS Med Chem Lett)
    The human epidermal growth factor receptor type 2 (HER2)-positive BC accounts for ∼15% of all BCs and a relatively poor prognosis. The disclosure in this patent highlight relates to a combination therapy comprising inavolisib (GDC-0077) and a HER2-targeted therapy such as trastuzumab, pertuzumab, or their combination for the treatment of HER2-overexpressing breast cancer.
    Journal • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 overexpression
    |
    Herceptin (trastuzumab) • Perjeta (pertuzumab) • inavolisib (GDC-0077)
    1year
    Enhanced efficacy of ARV-471, a novel PROTAC® estrogen receptor degrader, in combination with targeted agents in estrogen receptor-positive (ER+) breast cancer models (AACR 2023)
    In vitro studies revealed evidence of synergistic interactions between ARV-471 and the CDK4/6 inhibitors abemaciclib and ribociclib, the mTOR inhibitor everolimus, or the PIK3CA inhibitors alpelisib and inavolisib in ER+ breast cancer cells. ARV-471 also displayed greater anti-tumor activity in combination with abemaciclib, ribociclib or inavolisib than that observed with fulvestrant in combination with these agents. Taken together, these data suggest the potential utility of ARV-471 as a combination partner for clinically relevant targeted agents for treatment of early and late-stage ER+ disease.
    Clinical • Preclinical • Combination therapy
    |
    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    ER positive • PIK3CA mutation • ER Y537S • ER D538G • ESR1 mutation • CDK4 mutation
    |
    everolimus • Piqray (alpelisib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • vepdegestrant (ARV-471) • inavolisib (GDC-0077)
    1year
    Genomics Guided Targeted Post-neoadjuvant Therapy in Patients With Early Breast Cancer (COGNITION-GUIDE) (clinicaltrials.gov)
    P2, N=240, Not yet recruiting, German Cancer Research Center | Initiation date: Dec 2022 --> May 2023
    Trial initiation date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • TMB-H • HR positive • MSI-H/dMMR • HER-2 negative • PIK3CA mutation • HER-2 exon 20 insertion • PD-L1 amplification • HR positive + HER-2 negative • HER-2 exon 20 mutation • UGT1A1*28 • UGT1A1*1*1 • HER-2 exon 23 mutation
    |
    Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Perjeta (pertuzumab) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    1year
    INAVO121: A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (clinicaltrials.gov)
    P3, N=400, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting | Trial completion date: Aug 2029 --> Mar 2029 | Trial primary completion date: May 2028 --> Mar 2029
    Enrollment open • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 negative • PIK3CA mutation
    |
    Piqray (alpelisib) • fulvestrant • inavolisib (GDC-0077)
    over1year
    Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic or Inoperable Locally Advanced Triple-Negative Breast Cancer (clinicaltrials.gov)
    P1/2; N=280 --> 133
    Enrollment change • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PD-L1 expression • PIK3CA mutation
    |
    VENTANA PD-L1 (SP142) Assay
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Verzenio (abemaciclib) • albumin-bound paclitaxel • Kisqali (ribociclib) • fulvestrant • Halaven (eribulin mesylate) • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • inavolisib (GDC-0077) • Actemra IV (tocilizumab) • ladiratuzumab vedotin (SGN-LIV1A) • selicrelumab (RG7876)
    over1year
    MiRaDoR: A PoC Study to Evaluate Treatments’ Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population (clinicaltrials.gov)
    P2 | N=1260 | Not yet recruiting | Sponsor: MedSIR
    New P2 trial • Minimal residual disease • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • MammaPrint • Oncotype DX Breast Recurrence Score®Test
    |
    Verzenio (abemaciclib) • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    over1year
    GeparPiPPa: Neoadjuvant Endocrine Therapy +/- the PI3K Inhibitor Inavolisib in HER2+, HR+, PIK3CA Mutant Early Breast Cancer (clinicaltrials.gov)
    P2, N=170, Recruiting, German Breast Group | Not yet recruiting --> Recruiting | Trial completion date: Jun 2026 --> Jan 2027 | Initiation date: Jun 2022 --> Jan 2023 | Trial primary completion date: Mar 2026 --> Oct 2026
    Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)
    |
    HER-2 positive • PIK3CA mutation • ER positive + PGR positive • PGR positive • PGR positive + HER-2 positive
    |
    Herceptin (trastuzumab) • tamoxifen • inavolisib (GDC-0077) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    over1year
    A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation (clinicaltrials.gov)
    P1a/1b, N=498, Recruiting, Genentech, Inc. | Trial completion date: Aug 2023 --> Nov 2024 | Trial primary completion date: Aug 2023 --> Nov 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • erlotinib • divarasib (RG6330) • inavolisib (GDC-0077) • migoprotafib (RLY-1971)
    over1year
    GO39374: To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer (clinicaltrials.gov)
    P1, N=256, Recruiting, Genentech, Inc. | Trial completion date: Dec 2022 --> Nov 2024 | Trial primary completion date: Nov 2022 --> Nov 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation
    |
    Herceptin (trastuzumab) • Ibrance (palbociclib) • Perjeta (pertuzumab) • fulvestrant • letrozole • metformin • inavolisib (GDC-0077)
    over1year
    INAVO121: A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (clinicaltrials.gov)
    P3, N=400, Not yet recruiting, Hoffmann-La Roche
    New P3 trial • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 negative • PIK3CA mutation
    |
    Piqray (alpelisib) • fulvestrant • inavolisib (GDC-0077)