Spotlight on Patritumab Deruxtecan (HER3-DXd) from HERTHENA Lung01. Is a Median PFS of 5.5 Months Enough in Light of FLAURA-2 and MARIPOSA?

Figures & data

Table 1 Efficacy and Safety of HER3-DXd Treating EGFR Mutated NSCLC Patients

Trial Name	U31402-A-U102	Herthena-Lung 01
Phase	I	II
Patient selection	Metastatic EGFR-mutated NSCLC	Metastatic EGFR-mutated NSCLC
Number of lines of previous treatment	Median of 4 (range, 1–9) prior lines of systemic therapy. 89% received prior osimertinib and 80% received prior PBC	Median of 3 (range, 1–11) prior lines of systemic therapy. Previously treated with EGFR TKI and PBC. 92.9% received osimertinib
Sample size	Dose escalation: 36 patients Dose expansion: 45 patients	Fixed dose arm: 225 patients Uptitration arm: 51 patients
Sites	Global	Global
Design	Dose escalation: HER3-DXd (once every 3 weeks): 3.2 mg/kg (n = 4), 4.8 mg/kg (n = 15), 5.6 mg/kg (n = 12), and 6.4 mg/kg (n = 5) Dose expansion: 5.6 mg/kg (n=45)	Arm 1: a fixed-dose regimen of HER3-DXd 5.6 mg/kg (n=225) Arm 2: an uptitration regimen: cycle 1 day 1, 3.2 mg/kg; cycle 2 day 1, 4.8 mg/kg; cycle 3 day 1; and subsequent cycles, 6.4 mg/kg (n=51)
ORR	39% (Pooled HER3-DXd 5.6 mg/kg) (n = 57)	29.8% (Fix dose of HER3-DXd 5.6 mg/kg) (n = 225)
DOR (Months)	6.9 (Pooled HER3-DXd 5.6 mg/kg) (n = 57)	6.4 (Fix dose of HER3-DXd 5.6 mg/kg) (n = 225)
PFS (Months)	8.2 (Pooled HER3-DXd 5.6 mg/kg) (n = 57)	5.5 (Fix dose of HER3-DXd 5.6 mg/kg) (n = 225)
OS (Months)	NE (Pooled HER3-DXd 5.6 mg/kg) (n = 57)	11.9 (Fix dose of HER3-DXd 5.6 mg/kg) (n = 225)
Grade 3–4 AE Rate	74% (Pooled HER3-DXd 5.6 mg/kg) (n = 57)	64.9% (Fix dose of HER3-DXd 5.6 mg/kg) (n = 225)
TEAE Associated Death Rate	7% (Pooled HER3-DXd 5.6 mg/kg) (n = 57)	1.8% (Fix dose of HER3-DXd 5.6 mg/kg) (n = 225)

Abbreviations: AE, adverse effect; DOR, duration of response; EGFR, Epidermal Growth Factor Receptor; NE, not estimable; NSCLC, Non-Small Cell Lung Cancer; ORR, objective response rate; OS, overall survival; PBC, platinum-based chemotherapy; PFS, progression-free survival; TEAE, treatment-emergent adverse event; TKI, tyrosine kinase inhibitors.

Table 2 Efficacy and Safety Comparison Among FLAURA2 and MARIPOSA

Trial Name	FLAURA-2	MARIPOSA
Phase	III	III
Patient selection	EGFR-mutated NSCLC	EGFR-mutated NSCLC
Line of therapy	First line	First line
Sample size	557 patients	1074 patients
Sites	Global	Global
Design	Arm A: Osimertinib + chemo (n=279) Arm B: Osimertinib (n=278)	Arm A: Amivantamab + Lazertinib (n=429) Arm B: Osimertinib (n=429) Arm C: Lazertinib (n=216)
Stratification factors	Race (Chinese-Asian/ non-Chinese Asian/ non-Asian), EGFR mutation (local/ central test), WHO PS 0/1	EGFR mutation types (Ex19del or L858R), Asian race, CNS metastases
ORR	A: 83% B: 76%	A: 86% B: 85%
DOR (Months)	A: 24 B: 15.3	A: 25.8 B: 16.8
PFS (months)	A: 29.4 B: 19.9	A: 23.7 B: 16.6 C: 18.5
OS (Months)	Immature	Immature
Grade 3–4 AE Rate	A: 64% B: 27%	A: 75% B: 43%
TEAE Associated Death Rate	A: 1.8% B: 0.4%	A: 8% B: 7%

Abbreviations: AE, adverse effect; CNS, Central Nervous System; DOR, duration of response; EGFR, Epidermal Growth Factor Receptor; NSCLC, Non-Small Cell Lung Cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PS, Performance Status; TEAE, Treatment-Emergent Adverse Event; WHO, World Health Organization.