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
• PolyDamas (NCT05908734) is an ongoing, open-label, multicenter, interventional, phase 1/2 study that aims to identify the recommended phase 2 combination dose (RP2CD) and evaluate the antitumor effect of RYBREVANT and cetrelimab combination therapy in patients with metastatic NSCLC. The primary endpoints are the incidence and severity of adverse events (AEs) per the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 (including dose-limiting toxicities [DLTs]) in phase 1 and the objective response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in phase 2.^2,3
  • The study is currently recruiting with a target enrollment of 80 patients.² Results have not yet been published.
• A preclinical study has evaluated the combinatorial activity of RYBREVANT and pembrolizumab in humanized head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC) mice models.⁴ 

clinical DATA

PolyDamas Study

Study Design/Methods

• This is an ongoing, open-label, multicenter, interventional, phase 1/2 study with a combination dose selection phase (phase 1) followed by an expansion phase (phase 2). It aims to identify the RP2CD and evaluate the antitumor effect of RYBREVANT and cetrelimab combination therapy in patients with metastatic NSCLC.^2,3
• Phase 1 will include approximately 20 patients and aims to identify the RP2CD for the combination therapy.^2,3
  • Patients will receive an intravenous (IV) infusion of RYBREVANT at either a low dose (700 mg for body weight <80 kg) or a high dose (1050 mg for body weight ≥80 kg). The first infusion will be split between cycle 1 day 1 and day 2. Subsequent infusions will be administered on day 8, day 15, and day 22, and then every 2 weeks (Q2W) from cycle 2. Cetrelimab IV infusion will be administered concomitantly from cycle 1 day 2 (after the day 2 infusion of RYBREVANT).
  • Doses will be escalated or de-escalated based on DLTs and the RP2CD will be determined.
• Phase 2 will include approximately 60 patients and aims to evaluate the antitumor effect of the combination therapy at the selected RP2CD.^2,3
  • Patients will remain on study treatment until disease progression, unacceptable toxicity, or until another criterion for treatment discontinuation is met.
  • This phase has 2 cohorts:
    • In cohort A (n=~30), patients with Exon 19 deletion or Exon 21 L858 substitution mutations and prior treatment with third-generation EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy will be included.
    • In cohort B (n=~30), patients with treatment-naïve NSCLC who had programmed cell death ligand 1 (PD-L1) expression levels of ≥50% and no driver mutations will be included.
• Primary endpoints²:
  • Phase 1: incidence and severity of AEs per NCI-CTCAE v5.0, including DLTs
  • Phase 2: ORR per RECIST v1.1
• Key secondary endpoints²:
  • Phase 1: incidence and severity of AEs per NCI-CTCAE v5.0 and clinical laboratory abnormalities
  • Phase 2: duration of response (DoR), disease control rate (DCR), progression-free survival (PFS) according to RECIST v1.1, overall survival (OS), incidence and severity of AEs, and clinical laboratory abnormalities
• The study is currently recruiting with a target enrollment of 80 patients.² Results have not yet been published.

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 16 April 2025.