[ASCO 2022] Leclaza+Rybrevant combo draws oncologists’ attention

CHICAGO, Ill. – The use of Yuhan Corp.’s anticancer drug Leclaza (lazertinib) in combination with Janssen’s Rybrevant (amivantamab), a bispecific antibody targeting EGFR and MET, drew much attention from international oncologists.

At the annual meeting of the American Society of Clinical Oncology in Chicago, researchers gave an oral presentation on the updated results of Cohort A of the CHRYSALIS-2 study, which evaluated Leclaza plus Rybrevant combo therapy in EGFR-mutated non-small cell lung cancer (NSCLC).

Patients in Cohort A had no more treatment options because the disease progressed after the standard therapy Tagrisso (osimertinib) and chemotherapy.

Rybrevant, in combo with Leclaza, showed a 33 percent objective response rate (ORR) and 9.6 months of duration of response (DoR) in this patient group, drawing much attention.

At ASCO 2022, Korea Biomedical Review sat down with Cho Byoung-chul, head of the Lung Cancer Center at Yonsei Cancer Center, to learn about the clinical significance of the CHRYSALIS-2 study results and why oncologists were so interested in Rybrevant plus Leclaza combo therapy.

Question: Why did ASCO again pick CHRYSALIS-2 results as an oral presentation?

Answer: We set the patient target as those who progressed after platinum-based chemotherapy following osimertinib. The study was on patients who did not have any other treatment option. The unmet clinical need is very clear in this patient group because they need effective therapy. This is why researchers worldwide are developing various therapies for this patient group. Rybrevant plus Leclaza combo draws particular attention because it is used regardless of biomarkers and is “chemo-free.”.

Q: How should we interpret the updated study results?

A: Rybrevant plus Leclaza combo showed 33 percent ORR in patients who progressed after first-line osimertinib and second-line chemotherapy and those who progressed after first-line EGFR TKI and second-line osimertinib and third-line chemotherapy. They had DoR for 9.6 months. So the therapeutic effect lasted for quite a long time in patients who responded to the treatment.

The median progression-free survival (PFS) was 5.1 months, which was unsatisfying. But it is encouraging that the combo therapy was effective in a broad patient population, not a group of particular gene-targeted patients.

This combo therapy is far superior to the existing cytotoxic anticancer drugs in terms of toxicity. So, we expect that Rybrevant plus Leclaza will become a useful option.

Q: What kind of journey remains to make Rybrevant plus Leclaza available for lung cancer patients?

A: We should verify the efficacy and safety of the combo therapy in a confirmatory clinical trial, and this journey has already begun. The global MARIPOSA-2 study began, and researchers are enrolling patients swiftly. The study aims to recruit 500 patients. A rapid patient enrollment shows that the unmet need is high.

MARIPOSA-2 for patients resistant to osimertinib and MARIPOSA for newly treated patients are ongoing. MARIPOSA finished enrolling 1,000 patients. Completing patient enrollment in a pandemic demonstrates international researchers’ keen interest in the Rybrevant plus Leclaza combo.

Q: When can we get the results of these studies?

A: MARIPOSA directly compares the combo with osimertinib in the first-line therapy, and the results are expected to come out in the second half of next year. If the results turn out to be positive, as many expect, there will be no phase 3 study to treat EGFR-mutated NSCLC in the first-line therapy for some time.

If the findings of MARIPOSA are positive, the median PFS will be 30 months or longer. If Rybrevant plus Leclaza overcomes the 30-month median PFS barrier, it won't be easy to develop a better treatment.

If the MARIPOSA study fails, it will show how difficult it is to outperform conventional therapies. Then, it won't be easy to test a new drug.