HARMONi
29 evidence topics · 13 sources
Objective
Comparative efficacy and safety objective
Location and study date
Enrollment interval
Study design
Eligibility criteria
HARMONi: central nervous system eligibility
ECOG performance status eligibility
Treatment
Induction and maintenance regimens
| Treatment phase | Quoted regimen |
|---|---|
| Initial treatment | “Ivonescimab 20 mg/kg Q3W”“+Pemetrexed 500 mg/m² Q3W”“+Carboplatin AUC 5 Q3W”“4 cycles (3 weeks/cycle)” |
| Maintenance | “Ivonescimab 20 mg/kg Q3W”“+Pemetrexed 500 mg/m² Q3W” |
Study outcomes
Rationale for using progression-free survival as a primary endpoint
Regulatory rationale for progression-free survival
Statistical analysis description
Number of participants (Planned and analyzed)
HARMONi: randomized population
HARMONi: primary progression-free survival analysis population
Primary overall survival significance boundary
Description of analysis sets
HARMONi: inclusion of HARMONi-A patients in the planned analysis
Minimum exposure for the safety analysis
Results
Participant disposition
Randomized participants per group
Baseline characteristics
HARMONi: geographic representation
Efficacy results
HARMONi: primary progression-free survival
HARMONi: progression-free survival hazard ratio
HARMONi: overall response rate
HARMONi: primary overall survival analysis, median survival
| Ivonescimab plus chemotherapy | Placebo plus chemotherapy |
|---|---|
| “16.8 months” | “14.0 months” |
HARMONi: primary overall survival analysis, statistical result
HARMONi: updated overall survival analysis
HARMONi: intracranial progression-free survival, baseline brain metastases
Health-related quality of life and patient-reported outcomes
Exploratory EORTC QLQ-C30 assessment
Safety results
Summary
The sponsor table retains randomized arm sizes of 219. The primary publication reports safety denominators of 218 treated participants per arm.
Treated participants per arm in the primary safety analysis
Study limitations
Summary
The primary PFS analysis included 345 participants, not all 438 randomized participants. The primary OS comparison did not meet its significance boundary. The later HR of 0.76 is a follow-up result and does not replace the primary OS test. Intracranial findings were exploratory and outside the multiplicity-controlled hierarchy. Because the analysis included third-generation TKI-treated participants from HARMONi-A, the two trials should not be pooled as independent populations. The comparator was chemotherapy alone, not another active post-TKI combination.