Itovebi (inavolisib) / Roche - LARVOL DELTA

Precision medicine in colorectal cancer: Personalizing treatment for improved outcomes? (ESMO-GI 2025) - "Other MTT: KRAS G12C inhibitor + Cetuximab (N=18), pan-RAS inhibitor for KRAS G12Cm (N=1), Encorafenib + Cetuximab (N=14) and Dabrafenib + Trametinib (N=1) for BRAF V600Em, Trastuzumab Deruxtecan (N=3) and Tucatinib + Trastuzumab for HER2m/a (N=1), Trametinib for MEKm (N=2), anti LGR5-EGFR bispecific antibody for EGFRm (N=1), Niraparib + Dostarlimab for ARID1Am (N=1), Alectinib for ALKf(N=1) and Inavolisib for PIK3CAm (N=1). Despite no obvious OS benefit of MTT due to small pts number and late MTT lines, this study highlights the different potential targetable MA in 28.9% of pts excluding non G12C RASm. Impact of novel RAS inhibitors and other MTT might change mCRC precision medicine."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • ALK • ARID1A • BRAF • KRAS

INAVOLISIB-INDUCED DIABETIC KETOACIDOSIS (CHEST 2025) - No abstract available

Metabolic Disorders

Cognition-Guide, a multicenter phase-II-Umbrella study to examine genomically controlled, post-neoadjuvant treatment in patients with early breast cancer and high risk of recurrence after neoadjuvant chemotherapy (DGS 2025) - "As part of cognition, tumorresidua after a neoadjuvant chemotherapy in patients with early BC and a high risk of relapse (TNBC/Her2+ BC with non-PCR; hr+/her2- BC with non-PCR and CPS-EG score ≥ 3 or OPN+ and CPS-EG score ≥ 2) Full genome/whche-exomes and RNA sequencing analyzed in order to proof of a suitable biomarker, a subsequent assignment to one of six treatment arms within Cognition-Guide (atezolizumab, inavolisib, IpaTasertib, Olaparib, Sacituzumab Govitecan, Trastuzumab) or-in contraindication or- missing biomarker - to enable a low -observation. 240 patients are recruited at at least 9 German locations to demonstrate an IDFS improvement of 10 %(Power 90 %, level of significance 5 %) compared to historical controls. Updated data will be presented at the time of the congress."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

INAVO120: A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (clinicaltrials.gov) - P2/3 | N=325 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2030 ➔ Jan 2028

Trial completion date • 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: Clinical evidence on the effectiveness and security of inavolisib (DGS 2025) - No abstract available

Clinical • Breast Cancer • Oncology • Solid Tumor

Successful therapy management with inavolisib: strategies and best practice (DGS 2025) - No abstract available

Breast Cancer • Oncology • Solid Tumor

Novel regimens for persistent/recurrent rare epithelial ovarian carcinomas (EOCs) selected according to biomarker status: ENGOT-GYN2/GOG-3051/BOUQUET phase II study results (ESMO-GC 2025) - P2 | "We report results from combination regimens including inavolisib (inavo, a PI3Kα-selective inhibitor), giredestrant (gire, an oral selective oestrogen receptor degrader [SERD]), CDK4/6 inhibitors, letrozole, bevacizumab (bev), olaparib and atezolizumab (atezo)...Results In PIK3CA-mutated rare EOC, the cORR with inavo + palbociclib (palbo) was 25% (4 partial responses all in pts with clear-cell [CC] tumours) and median progression-free survival (PFS) was 8 mo. Gire + abemaciclib (abema) showed a 5% cORR but sustained disease control and a 58% 6-mo PFS rate in ER+ (mostly low-grade serous [LGS]) EOC. In non-matched pts, atezo + bev + metronomic cyclophosphamide (cyclo) showed a 32% cORR, including complete responses in 1 pt with LGS and 1 with mucinous carcinoma; the cORR was 0% with inavo + olaparib...Editorial acknowledgement J. Kelly (Medi-Kelsey Ltd). Legal entity responsible for the study F. Hoffmann-La Roche Ltd."

Biomarker • P2 data • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • ER • 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

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

ETX-636, a novel allosteric pan-mutant-selective PI3Kα dual inhibitor and degrader with best-in-class potential (AACR 2025) - "Orthosteric ATP-competitive inhibitors, alpelisib and inavolisib, which inhibit both Wild-type (WT) and mutant PI3Kα, are approved in combination regimens for treating PIK3CA-mutant, HR+/HER2-, advanced or metastatic BrCA...In addition to greater biochemical selectivity for mutant PI3Kα over WT PI3Kα, ETX-636 has stronger target binding affinity, better on-target potency in biochemical and cellular pharmacodynamic assays, and demonstrates superior anti-tumor activity in vivo when compared to other allosteric, pan-mutant-selective PI3Kα inhibitors (i.e. RLY-2608 and STX-478)...In an ER-positive, HER2-negative, PI3Kα-mutant BrCA xenograft, ETX-636 is efficacious as a single agent and shows synergistic activity with fulvestrant, inducing tumor regression while being well-tolerated...In addition, based on pharmacokinetic, pharmacodynamic, efficacy, and toxicology studies, predicted human efficacious doses of ETX-636 are not projected to cause hyperglycemia. The preclinical..."

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 • BRCA • ER • HER-2 • PIK3CA

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

PERSEVERE: Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer (clinicaltrials.gov) - P2 | N=52 | Terminated | Sponsor: Bryan Schneider, MD | N=197 ➔ 52 | Trial completion date: Jan 2034 ➔ Dec 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2029 ➔ Oct 2024; Funder Decision

Circulating tumor DNA • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

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

Effect of caprine herpes virus-1 (CpHV-1) on cell viability and chemosensitivity in breast cancer cells. (ASCO 2025) - "We also examined CpHV-1's combination with Abemaciclib (A), Tucatinib (T), and Inavolisib (I) using MTS assays and Chou-Talalay analysis The CpHV-1 infection showed a time and dose-dependent cytotoxic effect in all BC cells without significantly affecting the normal cells. CpHV-1 demonstrates potential as an effective therapeutic agent for cancer treatment, particularly when combined with standard targeted therapies. This combination enhances sensitivity in BC cells, including triple-negative subtypes. While further research is required to fully understand the mechanisms underlying CpHV-1's infection, our findings underscore the promise of these combined therapies as a novel and effective strategy for BC."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Comparative analysis of PIK3CA mutation detection methods in the first-in-human phase 1/1b study of inavolisib. (ASCO 2025) - P1 | "These results, albeit from a small study, demonstrate the ability of both tissue- and blood-based PCR and NGS assays to robustly identify a similar patient population with PIK3CAmut HR+, HER2- mBC, who may benefit from an inavolisib-based therapy regimen. Differences in PIK3CAmut detection concordance between tissue- vs. blood-based assays may reflect mutational profiling of a single-biopsied lesion vs."

Biomarker • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Clinical investigators' (CIs) practice patterns for patients with hormone receptor-positive metastatic breast cancer (HR+ mBC) harboring PI3K/AKT/PTEN pathway abnormalities (PAPm). (ASCO 2025) - "The recent availability of capi and inavo has significantly affected current practice patterns, with the majority of CIs rapidly incorporating these therapies into their treatment algorithms for specific patient types. Future work is needed to explore how other factors (eg, age, comorbidities, HER2-low status) and rapidly emerging clinical trial findings (eg, EMBER-3) affect decision-making. A = anastrozole; IPF = inavolisib + palbociclib + fulvestrant; F = fulvestrant; AI = aromatase inhibitor; C = capivasertib; Alp = alpelisib; E = elacestrant"

Clinical • Metastases • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA • PTEN

Treatment patterns in HR+/HER2- metastatic breast cancer (MBC) with co-occurring PIK3CA and ESR1 mutations. (ASCO 2025) - "Clinical and treatment data, including PI3Ki (alpelisib, inavolisib or investigational agents) and/or SERDs (fulvestrant or oral agents) were abstracted. Prior CDK4/6i ≥ 12 m in patients with co-occurring mutations treated with a SERD was associated with significantly improved PFS, potentially reflecting a conditioning effect of prior therapy. The total PFS (PFS1 + PFS2) in patients treated with sequential targeted therapies was similar; however, small sample sizes and potential confounders in this retrospective cohort limit definitive interpretations. Larger prospective studies are needed to determine optimal sequencing strategies."

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

A single center experience of PIK3CA and AKT inhibitors in patients with hormone receptor positive metastatic breast cancer. (ASCO 2025) - "Funded by No funding sources reported Background: Currently there are 3 FDA- approved PI3K/AKT inhibitors: alpelisib, capivasertib and inavolisib...In addition, 12 pts received alpelisib or capivasertib after everolimus and mPFS of were 5.8m... The single center experience of PIK3CA/AKT inhibitors reflected clinical trial result with similar PFS. A lower rate of dose interruptions and lower rate of all grades diarrhea were observed in the real-world data. Prophylactic use of antidiarrhea agents may contribute to the finding although precautions need to be taken due to the retrospective chart review nature of this study."

Clinical • Metastases • Breast Cancer • Dermatology • Diabetes • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PIK3CA

Enhanced efficacy of inavolisib combined with anti-PD-1 or anti-HER2 antibody in treating brain metastases from breast cancer. (ASCO 2025) - "Alpelisib is the only approved PI3K inhibitor for treating PIK3CA mutation-positive breast cancer...In addition to the Inavolisib monotherapy and vehicle control groups, Inavolisib was combined with a PD-1 antibody or albumin-bound paclitaxel in the triple-negative model...However, overall, the combination with trastuzumab achieved unexpectedly good results, which were comparable to SHR-A1811 and superior to Tucatinib... Our findings suggest that the combination of the PI3K inhibitor Inavolisib with anti-PD-1 or anti-HER2 antibody therapy may offer an effective strategy for treating brain metastases in breast cancer. This discovery provides new insights and possibilities for improving treatment options in breast cancer brain metastasis. Further research is needed to validate the efficacy and safety of this combination therapy."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • PIK3CA • PTEN

Phase Ib study of inavolisib (INAVO) + weekly paclitaxel (wP) in patients (pts) with locally advanced/metastatic (LA/m) incurable solid tumors: Safety, pharmacokinetics (PK), and preliminary antitumor activity. (ASCO 2025) - "However, it has an unfavorable benefit–risk profile when given with pan-PI3K inhibitors or alpelisib. INAVO, a potent and selective PI3Kα inhibitor that also promotes mutated p110α degradation, was FDA approved in combination with palbociclib + fulvestrant for hormone receptor-positive, HER2-negative (HR+, HER2–), endocrine-resistant advanced breast cancer (BC) following recurrence on/after completing adjuvant endocrine therapy... In CO42800, INAVO + wP was well tolerated in pts with LA/m solid tumors, including those with a PIK3CA mutation, with no new safety signals or drug–drug interactions observed. Encouraging preliminary antitumor activity shown in pts with HR+, HER2– BC or TNBC supports further investigation."

Clinical • Metastases • P1 data • PK/PD data • Anemia • Breast Cancer • Diabetes • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • 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 | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Inavolisib Plus Palbociclib and Fulvestrant Improves OS in PIK3CA-Mutant, HR+/HER2– Breast Cancer (OncLive) - P3 | N=325 | INAVO120 (NCT04191499) | Sponsor: Hoffmann-La Roche | "The addition of inavolisib (Itovebi) to palbociclib (Ibrance) and fulvestrant (Faslodex) led to a statistically significant improvement in overall survival (OS) vs placebo plus palbociclib and fulvestrant in patients with PIK3CA-mutant, hormone receptor–positive, HER2-negative, endocrine-resistant advanced breast cancer, according to data from the final OS analysis of the phase 3 INAVO120 trial (NCT04191499) that were presented in a press briefing ahead of the 2025 ASCO Annual Meeting. At a median follow-up of 34.2 months, the median OS was 34.0 months (95% CI, 28.4-44.8) with inavolisib (n = 161) vs 27.0 months (95% CI, 22.8-38.7) with placebo (n = 164; stratified HR, 0.67; 95% CI, 0.48-0.94; P = .0190). The 6-, 12-, 18-, 24, and 30-month OS rates in the inavolisib arm were 96.8%, 87.0%, 74.3%, 65.8%, and 56.5%. The respective rates in the placebo arm were 90.1%, 76.7%, 67.2%, 56.3%, and 46.3%."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 19-22 May 2025 (European Medicines Agency) - "On 22 May 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Itovebi, intended for the treatment of adults with PIK3CA-mutated, oestrogen receptor (ER)-positive, HER2-negative locally advanced and metastatic breast cancer. The applicant for this medicinal product is Roche Registration GmbH. Itovebi will be available as 3 mg and 9 mg film-coated tablets."

CHMP • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models. (PubMed, Br J Cancer) - "Multi-node PI3K/AKT/mTOR pathway inhibition with serabelisib, sapanisertib and ISD is highly effective in preclinical models of endometrial and breast cancer, supporting continued clinical development in these and other solid tumours."

Journal • Preclinical • Breast Cancer • Endometrial Cancer • Oncology • Solid Tumor • EIF4EBP1 • PIK3CA

INAVO123: Phase III study of first-line (1L) inavolisib/placebo + a CDK4/6 inhibitor + letrozole (INAVO/PBO + CDK4/6i + LET) in participants (pts) with PIK3CA-mutated (mut), hormone receptor-positive (HR+), HER2-negative (HER2-), endocrine-sensitive advanced breast cancer (aBC) (ESMO-BC 2025) - P2/3, P3 | "INAVO120 (NCT04191499) showed that 1L treatment with INAVO + palbociclib (PALBO) + fulvestrant (FULV) resulted in a significantly improved progression-free survival (PFS) benefit v PBO + PALBO + FULV (stratified hazard ratio 0.43; 95% confidence interval [CI] = 0.32–0.59; p200 centres, globally."

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 • CDK4 • HER-2 • PIK3CA