Rybrevant-Leclaza combo improves response rate, duration in NSCLC

Yuhan Corp.’s new anti-cancer drug Leclaza (ingredient: lazertinib), in combination with Janssen’s Rybrevant (ingredient: amivantamab), raised the response rate and extended the duration of response in advanced non-small cell lung cancer (NSCLC) patients who failed previous treatment.

Researchers presented the results from the two phase 1 studies of Rybrevant, CHRYSALIS, and CHRYSALIS-2, at the mini oral session of the European Society for Medical Oncology (ESMO) Annual Congress 2021 virtual meeting, held from Sept. 16-21. The two studies tested Rybrevant in advanced NSCLC patients with epidermal growth factor receptor (EGFR) mutations.

Natasha Leighl, Lung Medical Oncology Lead at Princess Margaret Cancer Centre in Toronto, Canada, speaks on the results of the CHRYSALIS trial at the virtual European Society for Medical Oncology (ESMO) Annual Congress 2021, held from Sept. 16-21. (Source: ESMO 2021)

The phase 1 CHRYSALIS trial evaluated Rybrevant as monotherapy and in combinations with Leclaza or chemotherapy in patients with advanced NSCLC with various EGFR mutations.

The latest data is the outcome of the Rybrevant monotherapy and the combo of Rybrevant and Leclaza in NSCLC patients who have failed Tagrisso (osimertinib), a third-generation EGFR tyrosine kinase inhibitor (TKI).

The Rybrevant monotherapy cohort included 121 patients, and the Rybrevant plus Leclaza cohort, 45 patients. Patients in the two groups had similar baseline status but different stages of previous treatments and different proportions of EGFR/MET (mesenchymal-epithelial transition)-based resistance.

The results showed that the Rybrevant plus Leclaza group had a higher objective response rate (ORR) and a longer duration of response (DoR).

During the median 6.9-month follow-up, the Rybrevant monotherapy group’s ORR was 19 percent, and DoR, 5.9 months. In contrast, during the median 11.1-month follow-up, the combo group’s ORR was 36 percent, and DoR, 9.6 months.

The median treatment period of the Rybrevant monotherapy cohort was 3.7 months, among which the treatment response group had 8.3 months of antitumor activity. Thirty-six percent of all patients showed a response for at least six months. Seventeen percent of patients reported progression in the central nervous system, and 13 percent had new brain lesions.

The median treatment period of the combo group was 5.6 months, among which the treatment response group had 12 months of antitumor activity. Sixty-nine percent of all patients showed a response for at least six months. Only 7 percent reported progression in the central nervous system, and 4 percent, new brain lesions.

The safety profiles were consistent with previous trial data, and there was no new safety signal.

Natasha Leighl, Lung Medical Oncology Lead at Princess Margaret Cancer Centre in Toronto, Canada, who presented the results, said amivantamab and lazertinib combo after osimertinib targeted extracellular and catalytic domains of EGFR simultaneously.

Compared with amivantamab monotherapy, the combo demonstrated a higher anticancer activity, treatment response, and durability and potentially improved protection effect for the central nervous system, she said.

Following the presentation of the CHRYSALIS data, CHRYSALIS-2 trial results were also disclosed.

The phase 1 CHRYSALIS-2 trial evaluated Rybrevant and Leclaza combo in EGRF-mutated NSCLCL patients who have progressed after treatment with Tagrisso and platinum-based chemotherapy.

The outcome of the CHRYSALIS-2 study presented at ESMO 2021. (Source: ESMO 2021)

Patients included 80 people (target group) who received existing first and second-generation EGFR TKI for the first and second-line treatment, then Tagrisso, and then platinum-based chemotherapy. Patients also included 56 people (heavily pretreated group) with a higher treatment stage. The two groups had similar baseline status, except for the stages of treatment.

According to the results, ORR in 29 patients of the target group available for effectiveness evaluation was 41 percent, during the median follow-up of 4.6 months.

The median treatment period was 4.2 months, and the median time until the first treatment response was 1.4 months. Among 12 patients who responded, eight remained in the target group without disease progression until data cut-off. Among 12 patients who showed stable legions, five remained in the treatment group.

In 47 patients available for efficacy evaluation in the heavily pretreated group, the ORR was 21 percent during the median follow-up of 4.5 months. The median treatment period was 3.7 months, and the median time until the first treatment response was 1.5 months. All 10 patients who responded remained in the treatment group without disease progression until data cut-off. Out of 26 patients with stable legions, 10 remained in the treatment group.

The safety profiles of the amivantamab and lazertinib in this study were consistent with previously reported trial results, and there was no new safety signal.