Itovebi (inavolisib) / Roche - LARVOL DELTA

Real-world outcomes of targeted endocrine therapies in hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative breast cancer with central nervous system metastases (HOPA 2026) - "Key trials evaluating abemaciclib, palbociclib, ribociclib, inavolisib, alpelisib, elacestrant, and capivasertib either excluded patients with CNS metastases or enrolled them in low numbers, where intracranial efficacy could not be reported. Results are pending and will be available at the time of the presentation."

Clinical • Real-world • Real-world evidence • Breast Cancer • CNS Tumor • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Discovery and characterization of RGT-490, a mutant selective PI3Kα inhibitor (AACR 2026) - "Clinical use and efficacy of the approved PI3Kα inhibitors alpelisib and inavolisib are limited by the side effects associated with wild-type (WT) PI3Kα inhibition, prominently hyperglycemia, rash, stomatitis and GI toxicities. With potent activity and excellent selectivity, RGT-490 provides opportunity to reduce WT PI3Kα-associated toxicities, enable deeper target coverage and achieve further improved clinical efficacy in PI3Kα mutant patients. RGT-490 phase 1 study is planned 1H2026."

Breast Cancer • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • PIK3CA

Machine learning accelerates discovery of synergistic- PI3K-mTOR combinations for robust tumor growth inhibition in KRAS G12 mutant patient-derived xenografts (AACR 2026) - "Notably, a key synergistic combination—involving Everolimus or Tacrolimus (mTORi) paired with Inavolisib (PI3Ki)—translated directly to significant therapeutic benefit in the PDX setting.These findings validate our PDX-informed strategy for rapidly identifying clinically relevant, synergistic combinations. The demonstrated efficacy of the Everolimus/Tacrolimus + Inavolisib combination provides compelling preclinical evidence, establishing this dual-agent approach as a strong therapeutic candidate for clinical evaluation in KRAS G12 mutant solid tumors."

Clinical • Machine learning • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KAT6i prifetrastat combines with PI3K pathway inhibitors to drive superior efficacy in preclinical models of PIK3CA mutated ER+ BC (AACR 2026) - "In vitro drug combination studies demonstrate synergy between prifetrastat and several PI3Kα inhibitors including alpelisib and inavolisib as well as mutant selective PI3Kα inhibitors such as tersolisib across cell lines harboring PIK3CA helical or kinase domain mutations. Finally, the triple combination of prifetrastat + Fulvesterant with PI3Kα inhibitors drives deeper tumor growth inhibition in PIK3CA mutant ER+ PDX models in vivo. Overall, we find that KAT6A/B inhibitors can effectively be combined with PI3Kα inhibitors and endocrine therapy to further drive efficacy in PIK3CA-mutant ER+BC indicating that the triplet combination could present a promising therapeutic option for this population."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • KAT6A • KAT6B • PIK3CA

Identification and characterization of pan-mutant selective PI3Kα inhibitors with the capability of PI3Kα H1047R protein degradation (AACR 2026) - P3 | "Orthosteric inhibitors of PI3Kα, such as alpelisib and inavolisib, have been approved for the treatment of patients with advanced HR+/HER2− breast cancer... Several allosteric and potent pan-mutant PI3Kα inhibitors developed by TYK Medicines exhibited high selectivity over wild-type (WT) PI3Kα. Our observations revealed that the compounds inhibited AKT phosphorylation in the T47D (PI3Kα H1047R) cell line with an IC50 in the single-digit nanomolar range, demonstrating nearly 200 times more selectivity compared to SK-BR-3 (PI3Kα WT) cells at same time. In in vitro antiproliferative assays, the compounds displayed superior antiproliferative activity against various PI3Kα mutant cells, including T47D, HCC1954 (PI3Kα H1047R), and MCF7 (PI3Kα E545K), compared to STX-478 and RLY-2608."

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

Investigating the value of testing for actionable alterations and circulating tumor DNA in breast and colorectal cancers (AACR 2026) - "HR+/HER2- BC samples had AAs associated with approved matched therapy in 13 (54.2%) samples , which included PIK3CA mutations associated with alpelisib, capivasertib, and/or inavolisib (7 samples; 16.7%) and 1 ESR1 alteration. Other AAs associated with FDA-approved therapies are listed in the table. Detection of AAs associated with FDA-approved matched therapy in approximately half of samples tested for ctDNA suggests it may influence therapy selection and disease management."

Circulating tumor DNA • Breast Cancer • Colorectal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Inavolisib exhibits anti-proliferative effects in pre-clinical model of endometrioid endometrial cancer (AACR 2026) - "Inavolisib demonstrated potent anti-proliferative and anti-invasive effects in endometrioid EC cell lines. Inavolisib may be a novel treatment strategy in EC, a cancer well-known for alterations in the PIK3CA/mTOR pathway."

IO biomarker • Preclinical • Breast Cancer • Endometrial Cancer • Oncology • Solid Tumor • BCL2 • BCL2L1 • MCL1 • PIK3CA

Inavolisib demonstrates anti-tumorigenic effects in pre-clinical models of serous endometrial cancer (AACR 2026) - "Inavolisib exhibits potent anti-tumorigenic and anti-invasive effects in serous EC cell lines, suggesting that this novel agent is a promising therapeutic option worthy of further exploration in the treatment of aggressive serous ECs."

IO biomarker • Preclinical • Breast Cancer • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Solid Tumor • Uterine Cancer • AURKA • BAX • BCL2 • CASP3 • CCND1 • CDK4 • MCL1 • PIK3CA

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=242 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=580 | Recruiting | Sponsor: Hoffmann-La Roche | N=242 ➔ 580 | Trial completion date: May 2026 ➔ May 2028 | Trial primary completion date: May 2026 ➔ May 2028

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=242 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=133 ➔ 242 | Trial completion date: May 2024 ➔ May 2026 | Trial primary completion date: May 2024 ➔ May 2026

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=280 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2021 ➔ Jun 2022 | Trial primary completion date: Aug 2021 ➔ Jun 2022

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • PD-L1

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=280 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Mar 2023 ➔ Sep 2023 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=280 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2023 ➔ May 2024 | Trial primary completion date: Sep 2023 ➔ May 2024

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=280 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2022 ➔ May 2023 | Trial primary completion date: Jun 2022 ➔ May 2023

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • PD-L1

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=260 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1/2 trial • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • PD-L1

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=792 | Recruiting | Sponsor: Hoffmann-La Roche | N=580 ➔ 792 | Trial completion date: May 2028 ➔ Sep 2030 | Trial primary completion date: May 2028 ➔ Sep 2030

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

A Study Evaluating Single-agent Inavolisib, Inavolisib Plus Atezolizumab, and Inavolisib Plus Pembrolizumab in PIK3CA-Mutated Cancers (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2026 ➔ Sep 2028 | Trial primary completion date: Sep 2026 ➔ Sep 2028

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • PIK3CA

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 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=280 ➔ 133

Enrollment change • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

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=260 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2018 ➔ Mar 2018

Enrollment open • Trial initiation date • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • PD-L1

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=280 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2023 ➔ Jan 2023 | Trial primary completion date: May 2023 ➔ Jan 2023

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

CO46274: A Phase II Study Evaluating the Efficacy and Safety of Inavolisib plus Ribociclib plus Fulvestrant Versus Placebo plus Ribociclib plus Fulvestrant in Patients with Advanced Breast Cancer (clinicaltrialsregister.eu) - P1/2 | N=14 | Not yet recruiting | Sponsor: F. Hoffmann-La Roche AG

New P1/2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • PGR • 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

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: clinicaltrials@relaytx.com."

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

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