NCT07486648

Osimertinib Plus Capivasertib in NSCLC With PIK3CA/AKT1/PTEN Alterations Following Prior 1L Osimertinib

The Safety and Efficacy of Osimertinib Plus Capivasertib in EGFRm Advanced Non-small Cell Lung Cancer (NSCLC) Participants With PIK3CA/AKT1/PTEN Alterations Who Had Progressed on First-line Osimertinib Monotherapy or Plus Chemotherapy: a First-in-human, Phase Ib/Ⅱa Study (PRECISION)

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Sponsor: Shanxi Province Cancer Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn if Osimertinib plus Capivasertib works to treat EGFRm advanced non-small cell lung cancer (NSCLC) in participants with PIK3CA/AKT1/PTEN alterations after progression on first-line Osimertinib (monotherapy or plus chemotherapy). The main questions it aims to answer are: Part A: * Number of Dose-limiting toxicities (DLTs) * Adverse events (AEs)/serious adverse events (SAEs) (graded by CTCAE Version 5.0) * Recommended combined dose (RCD) Part B:Confirmed ORR assessed by the Investigator per RECIST 1.1 criteria. Participants will: Part A:Take Capivasertib twice daily from day 1 to 4 of a 7-day cycle, Osimertinib will be given orally QD(once daily) at 80 mg throughout the study treatment period. Part B: Take Osimertinib (80mg QD, continuously) and Capivasertib(RCD,orally BID from day1-day 4 in 7-day cycle , 4 days on /3 days off) till disease progression (PD) or unacceptable toxicity.

Detailed description

This is a two-stage study, consisting of Phase Ib dose-escalation, Phase IIa dose expansion. Safety will be intensively monitored in Part A. If RCD (Recommended combined dose) was not reached in Part A, Part B (dose expansion phase) would not be initiated. If RCD was reached in Part A, eligible patients in Part B will be enrolled and receive Osimertinib (80mg QD, continuously) plus Capivasertib (RCD, orally BID from day1-day 4 in 7-day cycle , 4 days on /3 days off) till disease progression (PD) or unacceptable toxicity, with the aim to further evaluate the safety, tolerability and efficacy in terms of ORR, DCR, DOR, PFS and OS. All participants (18 and above) will undergo screening (Day -28 to -1), treatment period (starting from Day 1) and post-intervention follow-up period (end of treatment visit, 30-day safety follow-up and survival follow-up). Dose escalation(Part A) will follow the classic "3+3" schema. The DLT observation period is 28 days post first dose of study treatment. Dose escalation will occur only after DLT observation period is completed for a minimum of 3 participants, relevant data has been reviewed within the Safety Review Committee (SRC), and the SRC approves dose escalation.

Conditions

• Lung Cancer (NSCLC)
• Lung Cancer (Non-Small Cell)
• Advanced Non-small-cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Capivasertib in combination with Osimertinib	Capivasertib 320/400 mg(twice daily from day 1 to 4 of a 7-day cycle ),Osimertinib 80 mg(once daily continuously),28 days per cycle

Timeline

• Start date: 2026-05-15
• Primary completion: 2028-10-15
• Completion: 2028-12-31
• First posted: 2026-03-20
• Last updated: 2026-03-24

Locations

2 sites across 1 country: China