REZILIENT3

19 evidence topics · 7 sources

Objective

Primary comparison

“assess progression-free survival in the zipalertinib plus chemotherapy arm versus the chemotherapy arm” (opens the source at this quote in a new tab)

Location and study date

Interim analysis announcement date

“Aug. 12, 2026” (opens the source at this quote in a new tab)

WCLC presentation date

“Session Date: Monday, September 14, 2026” (opens the source at this quote in a new tab)

Study design

Global randomized design

“multicenter, randomized, controlled, open-label global trial” (opens the source at this quote in a new tab)

Randomization ratio

“1:1” (opens the source at this quote in a new tab)

Eligibility criteria

Disease and prior-treatment setting

“previously untreated, locally advanced or metastatic non-squamous NSCLC” (opens the source at this quote in a new tab)

Permitted untreated CNS disease

“untreated, asymptomatic brain metastases up to 2 cm” (opens the source at this quote in a new tab)

Treatment

Experimental combination regimen

“zipalertinib 100mg BID plus chemotherapy” (opens the source at this quote in a new tab)

Crossover after progression in the chemotherapy arm

“could cross over to zipalertinib after disease progression” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using progression-free survival as the primary endpoint

Regulatory rationale for progression-free survival

“PFS can reflect tumor growth” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Randomized participants

Population	Participants
Total randomized	“279”
Zipalertinib plus chemotherapy	“140”
Chemotherapy alone	“139”

Description of analysis sets

Primary PFS assessment

“blinded independent central review” (opens the source at this quote in a new tab)

Pre-planned interim analysis: number of PFS events

“122” (opens the source at this quote in a new tab)

Formal intention-to-treat and safety analysis-set definitions

No evidence found.

Results

Participant disposition

No evidence found.

Baseline characteristics

Baseline brain metastases

Characteristic	Zipalertinib plus chemotherapy	Chemotherapy alone
Participants with brain metastases	“31.4%”	“31.7%”

Efficacy results

Earlier interim analysis announcement

“met its primary endpoint of progression-free survival (PFS) at a planned interim analysis.” (opens the source at this quote in a new tab)
“The trial will continue to monitor efficacy and safety.” (opens the source at this quote in a new tab)

Interim efficacy results

Endpoint	Zipalertinib plus chemotherapy	Chemotherapy alone
Median PFS, months	“14.5”	“8.5”
Objective response rate	“65.0%”	“40.3%”
Median DOR, months	“14.2”	“9.9”

Interim time-to-event comparisons

Analysis	Quoted value
PFS hazard ratio	“0.50”
PFS hazard ratio, 95% CI	“0.34-0.73”
PFS P value	“0.00015”
OS event maturity	“30%”
OS hazard ratio	“0.72”
OS hazard ratio, 95% CI	“0.42-1.23”

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

Grade ≥3 adverse events

Endpoint	Zipalertinib plus chemotherapy	Chemotherapy alone
Participants with grade ≥3 adverse events	“87.1%”	“54.4%”

Study limitations

Summary

Results are from a planned interim analysis. OS was 30% mature, and its 95% confidence interval included 1. The comparator was chemotherapy, not the amivantamab-containing combination recommended by ESMO. Open-label treatment and permitted crossover are additional considerations when interpreting subsequent outcomes.