Summary

• Data from a global pre-approval access (PAA) program in patients with epidermal growth factor receptor (EGFR) Exon 20 insertion (Exon20ins)-mutated advanced non-small cell lung cancer (NSCLC) who received treatment with RYBREVANT demonstrated that the time to treatment discontinuation (TTD) and antitumor responses were consistent with or within the range of clinical trial results.¹
  • At the data cutoff of October 29, 2021, the median TTD was 5.2 months (95% confidence interval [CI], 4.2-7.2).
  • Responses were observed across all insertion regions of EGFR Exon20ins mutations.
• At the data cutoff of June 10, 2022, the median TTD was 5.13 months (95% CI, 4.177.03). Responses were observed across all insertion regions of EGFR Exon20ins mutations.²

Clinical Data

A global PAA program (NCT04599712) was initiated in which patients with EGFR Exon20ins-mutated advanced NSCLC who did not qualify for or have access to clinical trials received RYBREVANT.¹

Study Design/Methods

• Patients with unresectable or metastatic NSCLC with EGFR Exon20ins mutations that progressed on or after platinum-based chemotherapy were eligible.
• Intravenous RYBREVANT (1050 mg [<80 kg] or 1400 mg [≥80 kg]) was administered once weekly for the first 4 weeks (cycle [C] 1 day [D] 1 and 2, C1D8, C1D15 and C1D22) and then every 2 weeks thereafter (C2D1, C2D15 and onwards) for 28-day cycles.
  • In C1, RYBREVANT was administered at a dose of 350 mg on D1 and 700 mg or 1050 mg on D2.
• TTD was estimated using the Kaplan-Meier method and included all patients who had a record of ≥1 drug supply.
• Physician-reported best response was evaluated for patients with ≥1 drug supply and analyzed by the site of insertion (helical region, near loop, and far loop).

Results

Patient Characteristics

• At the data cutoff of October 29, 2021, the median follow-up was 3.7 months.
• The analysis set consisted of 210 patients who received RYBREVANT across 115 sites in 18 countries (Asia, 66.7%; Europe, 19%; North America, 9.5%; South America, 4.8%), of which 77 patients had physician-reported response data; see Table: Patient Characteristics.

Efficacy

• Median TTD was 5.2 months (95% CI, 4.2-7.2).
  • Reasons for treatment discontinuation included imputed discontinuation from no drug resupply request (n=36), progressive disease (n=25), adverse events (n=5), other (n=5), and death (n=3).
  • There were no statistically significant differences in risk rate of TTD across subgroups based on age, Exon20ins testing method, and insertion region of Exon 20, with the exception of prior lines of treatment; see Table: Relative Risk of Treatment Discontinuation by Subgroups.

• Among 77 patients with physician-reported response data, partial response (PR) was reported in 24 (31.2%) patients.
• The clinical benefit rate (PR + stable disease and ≥1 drug resupply) was 75.3%.
• Responses were observed across all insertion regions of Exon 20; see Table: Response by Insertion Region of Exon 20 Among Patients With Physician-Reported Response Data.

Safety

• No new safety signals were identified.

Sabari et al (2022)² reported updated results (data cutoff: June 10, 2022) from the global PAA program for RYBREVANT.

Results

Patient Characteristics

• Median follow-up was 7.9 months.
• The analysis set consisted of 380 patients who received RYBREVANT across 215 sites in 23 countries (South Korea, 34.2%; Europe, 26.8%; other parts of Asia, 23.7%; North America, 11.6%; South America, 3.7%), of which 205 patients had a disease assessment; see Table: Patient Characteristics.

Efficacy

• Median TTD was 5.13 months (95% CI, 4.17-7.03).
  • Reasons for treatment discontinuation included disease progression (n=80), adverse events (n=14), transition to commercial RYBREVANT (n=10), withdrawal of consent (n=1), death (n=13), lapse of >45 days since the last supply (n=92), or other (n=16).
  • There were no statistically significant differences in risk rate of TTD across subgroups based on age, Exon20ins testing method, and insertion region of Exon 20. Patients who received 2 and ≥3 prior lines of treatment had a higher relative risk of discontinuation than patients who received 1 prior line; see Table: Relative Risk of Treatment Discontinuation by Subgroups.

• Among 205 patients with a disease assessment, PR was reported in 64 (31.2%) patients.
• The clinical benefit rate (PR + stable disease and ≥1 drug resupply) was 74%.
• Responses were observed across all insertion regions of Exon 20; see Table: Response by Insertion Region of Exon 20 Among Patients With a Disease Assessment.

Safety

• No new safety signals were identified.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 22 April 2024.