LOXO-783 / Eli Lilly - LARVOL DELTA

A first-in-human phase 1a/b trial of LOXO-783, a potent, highly mutant-selective, brain-penetrant, allosteric PI3Kα H1047R inhibitor in PIK3CA H1047R-mutant advanced breast cancer and other solid tumors: Results from the PIKASSO-01 study. (SABCS 2024) - P1 | "Phase 1b (ph1b) included the evaluation of LOXO-783 plus (+) endocrine therapy (ET: fulvestrant [F] / aromatase inhibitor [AI]), or LOXO-783 + paclitaxel (P) in PI3Ki-naïve/intolerant pts with PIK3CA H1047R aBC. LOXO-783 demonstrated proof of concept of mutant selectivity by entirely sparing hyperglycemia in the clinic, but exhibited high rates of diarrhea, limiting ability to achieve the optimal preclinical dose of LOXO-783."

Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PIK3CA

PIKASSO-01: A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Recruiting | N=193 ➔ 260

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

Identification and characterization of an allosteric and mutant-selective PI3Kα inhibitor (AACR 2025) - P1, P1/2 | "Orthosteric inhibitors of PI3Kα, such as alpelisib and inavolisib have been approved for the treatment of patients with advanced HR+/HER2− breast cancer. TY-2291 is a potent kinase inhibitor of mutant PI3Kα with high selectivity over WT PI3Kα. In in vitro antiproliferative test, TY-2291 showed better antiproliferative activity against multiple PI3Kα mutant cells than LOXO-783, STX-478, and RLY-2608. In the mouse HCC1954 CDX model, TY-2291 showed potent tumor-inhibitory activity and excellent tolerance."

Breast Cancer • Colon Cancer • Colorectal Cancer • Gastric Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer • HER-2 • PIK3CA

PIKASSO-01: A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=193 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

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

PIKASSO-01: A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=193 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: May 2025 ➔ Dec 2025

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

PIKASSO-01: A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=193 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: May 2025 ➔ Dec 2025

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

Lilly to Present…Additional Results from Its Breast Cancer Portfolio at the San Antonio Breast Cancer Symposium (PRNewswire) - "Additional presentations from investigational mutant selective PI3Ka inhibitor assets include preclinical characterization data for LY4045004, which is expected to enter the clinic in the first half of 2025, and Phase 1a/b clinical data for a predecessor molecule, LOXO-783, which informed the development of LY4045004."

New trial • P1 data • Preclinical • Breast Cancer

PIKASSO-01: A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=193 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting | N=400 ➔ 193

Combination therapy • Enrollment change • Enrollment closed • Metastases • Monotherapy • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

A Study of [14C]-LOXO-783 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Completed

Trial completion

A Study to Evaluate the Effect of Food on LOXO-783 in Healthy Participants (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed

Trial completion

A Study of [14C]-LOXO-783 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

A Study to Evaluate the Effect of Cholestyramine on LOXO-783 in Healthy Participants (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Jul 2023 | Trial primary completion date: Dec 2023 ➔ Jul 2023

Trial completion • Trial completion date • Trial primary completion date

A Study to Evaluate the Effect of Food on LOXO-783 in Healthy Participants (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Eli Lilly and Company

New P1 trial

A Study to Evaluate the Effect of Cholestyramine on LOXO-783 in Healthy Participants (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Eli Lilly and Company

New P1 trial

PIKASSO-01: A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=400 | Recruiting | Sponsor: Eli Lilly and Company | N=300 ➔ 400

Combination therapy • Enrollment change • Metastases • Monotherapy • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

LOXO-783: A potent, highly mutant selective and brain-penetrant allosteric PI3Kα H1047R inhibitor in combination with standard of care (SOC) treatments in preclinical PI3Kα H1047R-mutant breast cancer models (SABCS 2022) - P1 | "Results Combining LOXO-783 with either fulvestrant (FUL; CI at 50% inhibition = 0.28) or imlunestrant (CI at 50% inhibition = 0.43) showed increased efficacy in cell proliferation assays using the HR+, HER2-, PI3Kα H1047R- mutant T47D model...Similar results were observed in a T47D model engineered to express ESR1 D538G, as well as in an HR+, HER2- PI3Kα double in-cis mutant model (H1047R/D350G) also harboring ESR1 D538G and derived from a patient who had progressed on prior letrozole plus taselisib...Extending these studies to additional treatment settings, LOXO-783 was similarly efficacious as a single agent in abemaciclib-resistant and abemaciclib/FUL double-resistant models, and was additive in combination with paclitaxel in a triple negative breast cancer model in vitro and in vivo...LOXO-783 is also efficacious in ESR1 mutant as well as in abemaciclib and abemaciclib/FUL double-resistant models. A phase 1 trial of LOXO-783 alone or in combination with..."

Combination therapy • Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PIK3CA

A phase 1 trial of LOXO-783, a potent, highly mutant-selective, brain-penetrant allosteric PI3Kα H1047R inhibitor in PIK3CA H1047R-mutant advanced breast cancer (aBC) and other solid tumors (PIKASSO-01, trial in progress) (SABCS 2022) - P1 | "Table. Dose Expansion (Phase 1b)"

P1 data • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Lilly Announces Details of Presentations at 2022 San Antonio Breast Cancer Symposium (PRNewswire) - "Eli Lilly and Company...announced that study investigators will present data from its breast cancer portfolio and pipeline at the 2022 San Antonio Breast Cancer Symposium (SABCS), to be held December 6-10, 2022....In a spotlight poster discussion, combination therapy results with imlunestrant will be presented from the Phase 1 EMBER trial of imlunestrant in combination with Verzenio, with or without an aromatase inhibitor, in patients with estrogen receptor positive (ER+), HER2- advanced breast cancer. In addition, pharmacodynamic data from the preoperative EMBER-2 trial evaluating imlunestrant in ER+, HER2- early breast cancer will be provided. Preclinical data with LOXO-783 in combination with standard-of-care breast cancer agents will also be presented at the meeting."

P1 data • PK/PD data • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Not yet recruiting | Sponsor: Eli Lilly and Company

Combination therapy • Monotherapy • New P1 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA