The author is an analyst for NH Investment & Securities. He can be reached at pk.park@nhqv.com -- Ed.
The MARIPOSA study has proven the feasibility of lazertinib+amivantamab as a standard first-line treatment. Competing trial FLAURA2 is expected to underperform in terms of OS. In addition, ESMO clinicians are de-emphasizing the importance of absolute PFS values, noting that MARIPOSA’s study design naturally results in a weaker PFS (vs FLAURA2).
Importance of OS vs PFS in MARIPOSA trial
Although maintaining a Buy rating, we lower our TP on Yuhan Corp by 8% to W115,000. In our view, the MARIPOSA-2 results point to a lower market share for Yuhan in secondary treatment. However, the MARIPOSA data also suggest a rise in Yuhan’s monotherapy market share in EMs, including Korea, as well as the possibility of amivantamab+lazertinib becoming a standard combination therapy for EGFR mutation in non-small cell lung cancer (NSCLC).
At ESMO, Yonsei University professor Cho Byeong-cheol announced phase III MARIPOSA data for the first-line treatment of EGFR-mutated NSCLC. Highlights included: 1) an improvement in modified progression-free survival (mPFS) regardless of brain metastasis; and 2) confirmation of a favorable overall survival (OS) trend, pointing to the possibility of a new standard treatment. However, as Grade 3 or higher adverse reactions jumped by 32%p, deaths due to adverse reactions climbed by 1%p, and treatment discontinuation upped by 7%p versus previously disclosed data, safety looks to be the next hurdle for MARIPOSA.
During discussion, it was mentioned that in order for MARIPOSA to result in a new standard first-line treatment, OS values, which are interim data, must be tracked further, with emphasis being placed on OS rather than progression-free survival (PFS). In particular, it was indicated that the PFS of FLAURA2 and MARIPOSA, which have been compared extensively in the domestic market, should not be directly contrasted due to differences in the number of diagnoses and primary evaluation index analysis. As MARIPOSA had a higher frequency of MRI and CT compared to FLAURA2, absolute PFS was inevitably lower.
Meanwhile, mPFS for lazertinib alone came to 18.5 months, showing absolute improvement versus Tagrisso (16.6 months). Although we do not have a p-value, this is the first test of the two products alone in the same clinical trial. Considering economic feasibility, the position of lazertinib is strengthening.
MARIPOSA-2 successful, but lazertinib results slightly disappointing
Encouraging results also arrived from the phase III MARIPOSA-2 study on Tagrisso-resistance. But, the combo of lazertinib+amivantamab+chemotherapy was similar to the simple combination of amivantamab+chemotherapy in improving PFS (including intracranial PFS), and although it is still early, rather disappointing data were reported for hazard ratio (HR) in OS. In addition, considering the increased toxicity, the use of lazertinib as a second-line treatment will likely be limited, as lazertinib and Tagrisso are competitors.
However, as Janssen’s first-line treatment market share increases, the number of Tagrisso-resistant patients should decline, given that Tagrisso competes with lazertinib. We expect Janssen to apply for FDA approval for both single and combined use of lazertinib for first-line treatment purposes this year.