SUMMARY  

• RYBREVANT (amivantamab-vmjw) is a low fucose, fully-human immunoglobulin G1 (IgG1)-based bispecific antibody with immune cell-directing activity that targets epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) mutations and amplifications in non-small cell lung cancer (NSCLC).¹
• No clinical studies were identified in the published literature that are designed to prospectively evaluate sequencing strategies for RYBREVANT and immunotherapy in the treatment of NSCLC.
• In the ongoing phase 1 CHRYSALIS study in which 114 patients in the safety population with metastatic or unresectable NSCLC and EGFR Exon 20 insertion (Exon20ins) mutations with disease progression during or after platinum-based chemotherapy were treated with RYBREVANT at the recommended phase 2 dose (RP2D), a total of
  49 patients received prior immunotherapy.^2,3
  • In a subgroup analysis of overall response rate (ORR) in the efficacy population (n=81) based on blinded independent central review (BICR) with a median follow-up of 9.7 months, the ORR was 46% (95% confidence interval [CI], 30-63) among the 37 patients who received prior immunotherapy compared to 34% (95% CI, 21-50) among the 44 patients who did not receive prior immunotherapy. Safety results are not available on patients who received prior immunotherapy.²
  • In a subgroup analysis with a medium follow-up of 19.2 months (n=114), the ORR was 42% (95% CI, 28.2-56.8) among the 50 patients who received prior immunotherapy compared to 32.8% (95% CI, 21.6-45.7) among the 64 patients who did not receive prior immunotherapy. Safety results are not available on patients who received prior immunotherapy.⁴
• In the wild-type (no EGFR, ALK, or MET Exon 14 activating mutations) cohort of the CHRYSALIS study, 41 patients with adenocarcinoma (NSCLC) and 14 patients with squamous cell NSCLC who had received prior anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy and chemotherapy were treated with RYBREVANT at the RP2D.⁵
  • At a median follow-up of 6.2 months, the ORR among patients with adenocarcinoma and squamous cell carcinoma, respectively, was 7% (95% CI, 1.5-20) and 21% (95% CI, 5-51), while the median duration of response (DOR) was 4.2 months (95% CI, 4.1-not estimable [NE]) and NE.
  • Among patients with adenocarcinoma and squamous cell carcinoma, respectively, grade ≥3 treatment-related adverse events (TRAEs) were reported in 17% and 21% of patients, and TRAEs led to treatment discontinuation in 4 (10%) and 2 (14%) patients.
    • Pneumonia was the most common grade ≥3 AE, reported in 5 (12%) and 3 (21%) patients with adenocarcinoma and squamous cell carcinoma, respectively.
    • Grade 2 interstitial lung disease was reported in 1 patient with adenocarcinoma.

CLINICAL DATA

To provide the most relevant information, the summary below is limited to information with the RP2D of RYBREVANT in a pivotal phase 1 study in patients with metastatic or unresectable NSCLC and Exon20ins mutations with disease progression during or after platinum-based chemotherapy.

Phase 1 Study in Patients with Metastatic or Unresectable NSCLC and Exon20ins Mutations with Disease Progression During or After Platinum-Based Chemotherapy (CHRYSALIS)

CHRYSALIS (NCT02609776) is an ongoing phase 1, open-label, multicenter, dose escalation and dose expansion study evaluating the safety, efficacy, and pharmacokinetics of RYBREVANT as monotherapy and in combination with other therapies in adult patients with advanced NSCLC harboring EGFR mutations who had disease progression during or after previous standard of care (SOC) treatment. A total of 114 patients with metastatic or unresectable NSCLC and EGFR Exon20ins mutations with disease progression during or after platinum-based chemotherapy were evaluated for safety, and 81 evaluable patients were assessed for efficacy. Patients received RYBREVANT at the RP2D: 1050 mg (<80 kg) or 1400 mg (≥80 kg) intravenously (IV) once weekly (QW) for cycle 1 and every 2 weeks (Q2W) thereafter until disease progression or unacceptable toxicity. Median follow-up for efficacy was 9.7 months (range, 1.1-29.3 months) and 5.1 months (range, 0.2-29.3) for safety.^2,6

A total of 49 patients (43.0%) in the safety population received one or more prior immunotherapy, including pembrolizumab (n=22; 19.3%), nivolumab (n=13; 11.4%), atezolizumab (n=10, 8.8%), durvalumab (n=3, 2.6%), tremelimumab (n=1; 0.9%) and
5 different investigational immunotherapy drugs (n=1 each; 0.9%).³

• For patients enrolled in CHRYSALIS, treatment with immunotherapy must have been stopped within 2 weeks or 4 half-lives (whichever was longer) before the first administration of RYBREVANT. For agents with long half-lives, the maximum required time since last dose to the start of RYBREVANT was 4 weeks.

In a subgroup analysis of ORR in the efficacy population (n=81) based on BICR with a median follow-up of 9.7 months, the ORR was 46% (95% CI, 30-63) among the 37 patients who received prior immunotherapy compared to 34% (95% CI, 21-50) among the 44 patients who did not receive prior immunotherapy. The ORR for the overall efficacy population was 40% (95% CI, 29-51). Safety results are not available on patients who received prior immunotherapy.²

In a long-term analysis of patients with EGFR Exon20ins mutations in CHRYSALIS cohort D with a median follow-up of 19.2 months (n=114), the ORR was 42% (95% CI, 28.2-56.8) among the 50 patients who received prior immunotherapy compared to 32.8% (95% CI, 21.6-45.7) among the 64 patients who did not receive prior immunotherapy. The ORR for the overall population was 36.8% (95% CI, 28-46.4). Safety results are not available on patients who received prior immunotherapy.⁴

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and DerwentDrug File (and/or other resources, including internal/external databases) was conducted on 25 June 2024.