ESMO on-site direct attack After the progression of ositinib, ositinib combined treatment "re-challenge", fast response within 6 weeks, ORR exceeded 50%

Editor: Xiaoyuan

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.

The European Society for Internal Oncology (ESMO) Annual Meeting is the most prestigious and influential oncology conference
in Europe.

In the oral presentation, Professor Julien Mazieres presented the preliminary findings
of the INSIGHT2 study for the first time.

Professor Julien Mazieres

1 Background

There is a lack of optimal treatment options after first-line ositinib therapy with advanced NSCLC of EGFR-sensitive mutations, and there is still a high degree of unmet clinical need
.

Schematic diagram of the mechanism of drug resistance

2 Methods

This is an open-label, Phase 2 study exploring the efficacy
of tepotinib+ ositinib in patients with MET amplification and EGFR-sensitive mutations NSCLC.

Study the design

MET amplification detection

3 Results

As of April 26, 2022, of the 425 pre-screened patients, MET amplification detected 139 patients (33%) (33%) and 47 (11%) patients
detected by FISH TBx and NGS LBx, respectively.
100 patients were treated, 88 in the TEP+OSI group and 12 in the TEP group, 62% were female, the median age was 61 years, 56% were Asian, and 68% of patients had ECOG PS 1
.
At least 9 months of follow-up, 22 patients treated with tepotinib + oshitinib (FISH test MET) had an ORR of 54.
5%, and 6 patients (12 responders total) were still being treated
.
At least 3 months of follow-up, the ORR was 45.
8%
in 48 patients (FISH method to detect MET).
Combination therapy produced rapid response and long-term remission, with most patients responding within 6 weeks, half of the remission-reliever responding lasting longer than 6 months, and the median DOR was not reached
.

ORR results of combination therapy

Rapid response and sustained remission of combination therapy

Of the 12 patients treated with TEP (FISH to detect MET), the optimal total response (BOR) was that one patient achieved partial remission (PR) with an ORR of 8.
3%.

Seven patients crossed to the TEP+OSI group as the disease progressed, and five patients continued to be treated
.

Of the 88 patients treated with TEP+OSI, 65 (73.
9%)/21 (23.
9%) had any grade 3 or above treatment-related adverse events (AEs) (> 15% of patients: diarrhea 40.
9% vs 0%, peripheral edema 23.
9% vs 4.
5%, paronychia 17.
0% vs 1.
1%)
.

Security analysis

4 Conclusion

Preliminary analysis of INSIGHT 2 showed that after the advancement of first-line ositinib therapy, ositinib + tepotinib was very effective and well
tolerated in patients with MET amplification (confirmed by TBx FISH) and positive NSCLC of EGFR mutation.
The study suggests that FISH MET GCN≥5 and/or MET/CEP7 ratios ≥2 (TBx samples) as defined by MET amplification positive populations and patients with EGFR-sensitive mutations can produce clinically meaningful responses
with this combination regimen.
This protocol may meet the clinical needs
of patients with MET amplification and EGFR mutation NSCLC after the progression of first-line ositinib therapy.

References

LBA52-Tepotinib + osimertinib for EGFRm NSCLC with MET amplification （METamp） after progression on first-line （1L） osimertinib: Initial results from the INSIGHT 2 study.
2022 ESMO.