Itovebi (inavolisib) / Roche - LARVOL DELTA

Phase I/Ib study of inavolisib (INAVO) alone and in combination with endocrine therapy ± palbociclib (PALBO) in patients (pts) with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced/metastatic breast cancer (HR+, HER2– LA/mBC): Analysis of hyperglycemia (HG) in prediabetic/obese pts. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03006172 Background: INAVO, a highly potent and selective PI3Kα inhibitor that also promotes degradation of mutated p110α, is approved by the FDA in combination with PALBO + fulvestrant (FULV) for PIK3CA-mutated, HR+, HER2–, endocrine-resistant advanced BC... Adults ≥ 18 years of age received INAVO alone (Arm A), + letrozole (LET) + PALBO (Arm B), + LET (Arm C), + FULV (Arm D), + FULV + PALBO (Arm E), or + FULV + PALBO + primary prophylactic metformin (Arm F)...The most common anti-HG medications were metformin (52.7%; biguanide; concomitant use in Arm F excluded), empagliflozin (25.5%; SGLT-2 inhibitor), sitagliptin (22.7%; DPP-4 inhibitor), and pioglitazone (13.6%; thiazolidinedione); insulin was used in 8.2% of pts... A high proportion of prediabetic/obese pts were included in GO39374. In most of these pts, HG was manageable with dose interruptions and oral anti-HG medications, most commonly metformin. Data support the use..."

Clinical • Combination therapy • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Obesity • Oncology • Solid Tumor • HER-2 • PIK3CA

MiRaDoR: A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population (clinicaltrials.gov) - P2 | N=976 | Active, not recruiting | Sponsor: MedSIR | Recruiting ➔ Active, not recruiting

Circulating tumor DNA • Enrollment closed • Minimal residual disease • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Real-World Effectiveness and Safety of the Novel Agent Inavolisib in Heavily Pretreated, PIK3CA-mut Advanced Breast Cancer:A Multicenter Study of Patients with More Advanced and Complex Disease (ESMO 2026) - No abstract available

Clinical • Metastases • Real-world • Real-world effectiveness • Real-world evidence • Breast Cancer • Oncology • Solid Tumor • PIK3CA

Real-World Treatment Patterns and Outcomes of Inavolisib in Breast Cancer Patients (ESMO 2026) - No abstract available

Clinical • HEOR • Real-world • Real-world evidence • Breast Cancer • Oncology • Solid Tumor

Updated interim analysis of giredestrant (GIRE) + inavolisib (INAVO) in MORPHEUS Breast Cancer (BC): A Phase Ib/II study of GIRE treatment (tx) combinations in patients (pts) with oestrogen receptor-positive, HER2-negative locally advanced/metastatic BC (ER+, HER2– LA/mBC) (ESMO 2026) - No abstract available

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

CNS distribution and preclinical activity of the PI3K/AKT inhibitors inavolisib and ipatasertib in pediatric-type diffuse high-grade gliomas. (PubMed, Cancer Chemother Pharmacol) - "These findings highlight the therapeutic potential of inavolisib for treating PIK3CA-mutated pHGG. Despite the blood-brain barrier, inavolisib achieved sufficient CNS exposure to prolong survival in preclinical models, whereas ipatasertib efficacy did not translate from in vitro to in vivo settings."

Journal • Preclinical • Brain Cancer • Diffuse Midline Glioma • Glioma • High Grade Glioma • Oncology • Pediatrics • Solid Tumor • PIK3CA

INAVO123: A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2032 ➔ Feb 2032 | Trial primary completion date: May 2032 ➔ Jan 2032

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

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) - P3 | "Clinicaltrials.gov number NCT05646862. This abstract was originally presented at ASCO 2023 (TPS1123)."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

INAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC). (ASCO 2025) - P2/3 | "INAVO + PALBO + FULV demonstrated a statistically significant and clinically meaningful OS benefit compared with PBO + PALBO + FULV. Improvement in INV-PFS was maintained during longer follow-up, along with a substantial and statistically significant improvement in ORR. TTC was also substantially delayed (by ~2 years) by the addition of INAVO to PALBO + FULV."

Clinical • Metastases • P3 data • Breast Cancer • Diabetes • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Efficacy of inavolisib (INAVO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative (HER2-), endocrine-resistant advanced breast cancer (aBC) with and without hyperglycaemia (HG) in the phase III INAVO120 trial (ESMO-BC 2026) - P2/3 | "Pts in the INAVO arm had consistently improved efficacy v PBO, regardless of whether they had HG or not. In the INAVO arm, pts w/ HG often had numerically improved efficacy outcomes v pts w/o HG, supporting INAVO benefit in these pts. Despite the relatively high prevalence of HG in the INAVO arm, glucose management allowed long-term INAVO tx."

Clinical • Metastases • P3 data • 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 • HER-2 • PIK3CA

First-line inavolisib/placebo + palbociclib + fulvestrant in PIK3CA-mutated, hormone receptor+, HER2- locally advanced/metastatic breast cancer w/ relapse during/within 12 months of adjuvant endocrine therapy completion: INAVO120 long-term safety (SABCS 2024) - P1 | "CONCLUSIONS The long-term safety profile of inavo + palbo + fulv in the populations on study tx for ≥1yr and ≥2yr was consistent with the INAVO120 SAS population reported previously, and similar to the long-term safety data of the phase 1 GO39374 study (NCT03006172). No new or unexpected AEs were reported."

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

First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2‑negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses. (ASCO 2024) - P2/3 | "Inavo+Palbo+Fulv was associated with sustained benefit beyond disease progression, delaying chemotherapy administration, with manageable safety and tolerability that was reflected in PROs; hence, supporting it as a new standard of care."

Clinical • Metastases • P3 data • Breast Cancer • Dental Disorders • Diabetes • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pain • Solid Tumor • Stomatitis • HER-2 • PIK3CA

US Food and Drug Administration Approval Summary: Inavolisib With Palbociclib and Fulvestrant for Endocrine-Resistant, PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, Locally Advanced or Metastatic Breast Cancer. (PubMed, J Clin Oncol) - "The approval of inavolisib with palbociclib plus fulvestrant was based on a statistically significant and clinically meaningful improvement in PFS observed in the INAVO120 trial. Before this approval, there were no specific therapies approved by the FDA for the first-line treatment of patients with endocrine-resistant, hormone receptor-positive advanced or MBC."

Clinical • FDA event • Journal • Breast Cancer • Dental Disorders • Diabetes • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

Inavolisib for PIK3CA-mutated advanced endometrial cancer: a multicentric, phase II, MITO END-4 trial. (PubMed, Int J Gynecol Cancer) - P2 | "Alpelisib, an oral PI3K alpha-selective inhibitor, showed encouraging preliminary activity in advanced gynecological tumors harboring PIK3CA alterations...Key exclusion criteria include uterine sarcoma and prior treatment with any PI3K, AKT, or mechanistic target of rapamycin (mTOR) inhibitor...May 2028. MITO END-4; EU-CT NUMBER: 2025-522981-61-00; NCT07522697."

dMMR • IO biomarker • Journal • P2 data • P53mut • pMMR • Carcinosarcoma • Endometrial Cancer • Gynecologic Cancers • Oncology • Sarcoma • Solid Tumor • PIK3CA • PTEN

reaINAVO: A Study to Evaluate the Effectiveness and Safety of Inavolisib in Participants With Endocrine-resistant, PIK3CA-mutated, Hormone Receptor-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - P=N/A | N=500 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2029 ➔ Dec 2029

Trial completion date • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. (PubMed, N Engl J Med) - P2/3 | "In patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.)."

Clinical • Journal • Metastases • Breast Cancer • Dental Disorders • Diabetes • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Mucositis • Neutropenia • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

ReDiscover-2, a phase 3 study of RLY-2608 + fulvestrant versus capivasertib + fulvestrant as treatment for locally advanced or metastatic PIK3CA-mutant HR+/ HER2- breast cancer following recurrence or progression on or after treatment with a CDK4/6 inhibitor (trial in progress) (SABCS 2025) - P3 | "While the PI3K inhibitors alpelisib and inavolisib and the AKT inhibitor capivasertib have been approved by the FDA to treat this substantial patient population, these therapies cause significant toxicity, notably hyperglycemia, rash, and diarrhea, due to their non-selective targeting of the pathway. Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication are excluded• No prior PI3K, AKT, or mTOR inhibitors or any agent whose mechanism of action is to inhibit the PI3K/AKT/mTOR pathwayReDiscover-2 (NCT06982521) is open for enrollment. For further information, contact: [email protected]."

Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • PTEN

GeparPiPPa: Neoadjuvant Endocrine Therapy +/- the PI3K Inhibitor Inavolisib in HER2+, HR+, PIK3CA Mutant Early Breast Cancer (clinicaltrials.gov) - P2 | N=170 | Recruiting | Sponsor: GBG Forschungs GmbH | Trial primary completion date: Oct 2026 ➔ Jan 2027

Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Risk-Stratified Management of Inavolisib-Induced Hyperglycemia and Patient Adherence (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: Tianjin Medical University Cancer Institute and Hospital

New trial • Real-world evidence • Breast Cancer • Diabetes • Oncology • Solid Tumor • HER-2 • PIK3CA

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=420 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2 • PIK3CA

Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer. (PubMed, N Engl J Med) - P2/3 | "Treatment with inavolisib plus palbociclib-fulvestrant led to a significant overall survival benefit, as compared with placebo plus palbociclib-fulvestrant. Hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxic effects, and ocular toxic effects were reported more frequently with inavolisib than with placebo. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.)."

Journal • Breast Cancer • Dental Disorders • Diabetes • Dry Eye Disease • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Mucositis • Oncology • Ophthalmology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

Safety overview and management of inavolisib alone and in combination therapies in PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer (GO39374). (PubMed, ESMO Open) - P1 | "Inavolisib alone or in combination with HR-positive breast cancer therapies demonstrated a manageable safety and tolerability profile, which supports its ongoing development."

Journal • Breast Cancer • Dental Disorders • Diabetes • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer. (PubMed, J Clin Oncol) - P1 | "Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity."

Journal • Metastases • P1 data • Breast Cancer • Dental Disorders • Diabetes • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

A Study to Test Inavolisib Treatments in Participants With Early-Stage, PIK3CA-Mutated Breast Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Hoffmann-La Roche | N=60 ➔ 120

Enrollment change • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

The Phosphatidylinositol 3-Kinase (PI3K) Inhibitor Inavolisib Has Breast-cancer Synergy Combined With Recombinant Methioninase But Not on Normal Cells. (PubMed, In Vivo) - "IVB had a very low IC50 on MCF-7 breast-cancer cells compared to Hs-27 normal fibroblasts. IVB had increased efficacy on MCF-7 breast-cancer cells when combined with rMETase, showing strong synergy. In contrast, the combination of rMETase and IVB showed no synergy on Hs-27 normal fibroblasts. Therefore, IVB in combination with rMETase has strong clinical potential for breast cancer and possibly other cancers."

Journal • Breast Cancer • CNS Disorders • Oncology • Psychiatry • Solid Tumor