Lilly's LOXO-783 breast cancer trial reopens enrollment after two-year pause
The Phase 1 PIK3CA inhibitor study returns to recruiting and lifts its enrollment target back to 260, as Lilly pushes its earlier-stage PI3K-alpha asset behind two more advanced internal programs.
Executive Summary
- A Phase 1 Eli Lilly trial testing LOXO-783 in PIK3CA-mutated breast cancer and other tumors returned to active recruitment after roughly two years as an active, non-recruiting study, and its enrollment target was restored to its original level.
- The enrollment change falls within the range the operational model treats as typical for an early-phase study, and no efficacy or safety result has posted, so the reopening itself carries limited information value on its own.
- Lilly already runs a more advanced PIK3CA-pathway program in the same indication, which narrows how much this earlier asset's outcome would move the company's own pipeline read.
- Trials targeting PIK3CA in breast cancer have a documented Phase 1 failure history and a dense competitive field, setting a demanding bar for any dose-finding data this cohort eventually produces.
The status change
NCT05307705, known as PIKASSO-01, shifted back to a status of Recruiting on July 20, 2026, after moving to Active, not recruiting in September 2024. Alongside that shift, its anticipated enrollment count rose from 193 to 260 patients, the same figure the trial carried when it first opened in 2022. The trial tests LOXO-783, an oral PIK3CA inhibitor, in patients with PIK3CA H1047R or other activating PIK3CA mutations across seven treatment arms spanning dose escalation and expansion cohorts in ER-positive, HER2-negative breast cancer and other advanced tumors. NCT05307705A Study of LOXO-783 in Patients With Breast Cancer/Other Solid TumorsNCT05307705
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the trial is testing
The study's primary endpoints are dose-limiting toxicities and DLT-equivalent events measured during the first 28-day treatment cycle, aimed at establishing a maximum tolerated dose and recommended Phase 2 dose for LOXO-783. Secondary measures include pharmacokinetics and preliminary antitumor activity, covering overall response rate, progression-free survival, and duration of response, assessed over as long as three years. No results have posted on the trial's ClinicalTrials.gov record, and the primary completion date now stands at December 1, 2026, after moving twice from an original target of May 2025. NCT05307705A Study of LOXO-783 in Patients With Breast Cancer/Other Solid TumorsNCT05307705
The pipeline position
LOXO-783 sits behind two more advanced Lilly programs targeting the same PI3K-alpha pathway: tersolisib (LY4064809/STX-478), which is already in a Phase 3 trial for PIK3CA-mutated advanced breast cancer, and an earlier Phase 1/2 study of STX-478 in tumors of multiple types. Beyond Lilly, the PIK3CA-in-breast-cancer field includes Roche's inavolisib and Novartis's alpelisib, both approved in this indication in combination regimens, alongside Phase 3 programs for AstraZeneca's capivasertib and Relay Therapeutics' RLY-2608. Inavolisib and capivasertib carry FDA approval in PIK3CA/AKT-altered, HR-positive, HER2-negative breast cancer specifically, while alpelisib's approval covers a different indication, PIK3CA-Related Overgrowth Spectrum, not this trial's population.
The historical bar
Across 14 Phase 1 trials targeting PIK3CA in breast cancer, 9 completed and 5 terminated, a 36% failure rate, and 7 distinct companies have discontinued programs in this target-indication pairing. Median trial duration for PIK3CA-in-breast-cancer studies at this phase runs 1,791 days, with enrollment typically taking 1,244 days to complete. Against that backdrop, the reopened cohort's dose-finding data would need to clear a maximum tolerated dose with a tolerability profile distinct enough to justify advancing LOXO-783 past Lilly's own more advanced PIK3CA-pathway candidate.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.