Section 4 of 6
Clinical evidence
69 evidence topics · 27 sources
Study summaries
REZILIENT1
Objective
Original phase 1/2a efficacy objective
Location and study date
Phase 1/2a data cutoff
Study design
REZILIENT1: phase 1/2 development program, NCT04036682
Original phase 1/2a cohort-transition design
Eligibility criteria
Performance status eligibility
Treatment
Investigational monotherapy regimen
Study outcomes
Rationale for using RECIST v1.1 objective response rate as the primary endpoint
Primary endpoints and blinded central review
Regulatory rationale for objective response
Statistical analysis description
Number of participants (Planned and analyzed)
Original phase 1/2a planned enrollment
Pivotal analysis populations
| Population | Quoted description |
|---|---|
| Primary efficacy population | “Primary efficacy population (N=176)” |
| Safety population | “Safety population (N=244)” |
Updated prior-amivantamab cohort: data cutoff and enrollment
Description of analysis sets
Primary efficacy population: minimum follow-up requirement
Results
Participant disposition
Pivotal safety population: treatment-related discontinuations, n (%)
Baseline characteristics
Pivotal safety population: baseline characteristics
| Characteristic | Value |
|---|---|
| Median age, years (range) | “65 (31–86)” |
| Female participants, n (%) | “157 (64)” |
Efficacy results
Phase 1/2a results at the selected dose
Pivotal results: prior platinum-based chemotherapy only
Updated prior-amivantamab cohort: prior amivantamab only
Pivotal progression-free and overall survival
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
Pivotal safety population: grade ≥3 treatment-related adverse events, n (%)
Pivotal treatment-related deaths
| Population | Endpoint | Result |
|---|---|---|
| “Safety population (N=244)” | “TRAE leading to death” | “2 (0.8)” |
Study limitations
Summary
The trial is open-label. Its pivotal efficacy population included 176 participants with approximately 8 months of minimum follow-up, whereas 244 participants formed the safety population. Prior-treatment cohorts and the later 84-participant amivantamab cohort have different eligibility histories and follow-up cutoffs. Their response estimates should not be treated as randomized comparisons or as interchangeable analyses. The phase 1/2a results are an earlier analysis of the same development program.
REZILIENT3
Objective
Location and study date
Interim analysis announcement date
WCLC presentation date
Study design
Randomization ratio
Eligibility criteria
Disease and prior-treatment setting
Permitted untreated CNS disease
Treatment
Experimental combination regimen
Crossover after progression in the chemotherapy arm
Study outcomes
Rationale for using progression-free survival as the primary endpoint
Regulatory rationale for progression-free survival
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
Primary PFS assessment
Pre-planned interim analysis: number of PFS events
Formal intention-to-treat and safety analysis-set definitions
No evidence found.
Results
Participant disposition
No evidence found.
Baseline characteristics
Efficacy results
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
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.
REZILIENT2
Objective
Location and study date
Cohort C data cutoff
Study design
Eligibility criteria
Active CNS metastases: molecular population
Treatment
Cohort C dose and administration
Study outcomes
Rationale for using RECIST v1.1 objective response rate as the primary endpoint
Investigator-assessed systemic primary endpoint
Statistical analysis description
Number of participants (Planned and analyzed)
Cohort C enrollment
| Population | Participants |
|---|---|
| Total enrolled | “32” |
Description of analysis sets
Results
Participant disposition
No evidence found.
Baseline characteristics
Cohort C biomarker population
| Characteristic | Participants, n (%) |
|---|---|
| EGFR exon 20 insertion mutations among all 32 participants | “21 (66)” |
Efficacy results
Active CNS metastases: intracranial response
Additional cohort C response results
| Endpoint | Value |
|---|---|
| Confirmed systemic responses, n/N (%) | “8/29 (27.6%)” |
| Median intracranial DOR, months | “8.1” |
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
Study limitations
Summary
The cohort enrolled 32 participants, of whom 21 (66%) had EGFR exon 20 insertions. Systemic response was reported in 8 of 29 evaluable participants and intracranial response in 5 of 16. These are different analysis populations, and the pooled results are not restricted to exon 20 insertions. The ongoing phase 2b cohort does not provide a randomized treatment comparison.
REZILIENT4
Objective
Adjuvant treatment objective
Location and study date
UK research ethics opinion date
Study design
Adjuvant development phase
Randomization, masking, and multicenter design
Eligibility criteria
Treatment
Study-drug dosing frequency
Maximum total study-drug treatment duration
Study outcomes
Rationale for using disease-free survival as the primary endpoint
Regulatory setting for disease-free survival endpoints
Statistical analysis description
Number of participants (Planned and analyzed)
Planned enrollment, participants
Description of analysis sets
No evidence found.
Results
Participant disposition
No evidence found.
Baseline characteristics
No evidence found.
Efficacy results
No evidence found.
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
No evidence found.
Study limitations
Summary
The report contains trial-design information, not results. Eligibility covers uncommon EGFR mutations rather than exon 20 insertions alone, and the planned enrollment is 360 participants. No efficacy or safety estimate can be drawn from these protocol details.