EGFR Exon 20 NSCLC - October 2020

EGFR Exon 20 NSCLC - October 2020

Rain Therapeutics presents positive results for RAIN-701 study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations & other solid tumors with NRG1/ERBB gene fusions

18 Sep 2020

Tarloxotinib (pan-ErbB tyrosine kinase inhibitor) – Rain Therapeutics

  • Rain Therapeutics presented the first positive results of tarloxotinib from the Phase 2 RAIN-701 trial in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations & other solid tumors with NRG1/ERBB gene fusions at ESMO2020
  • This trial consists of three cohorts:
    • Cohort A – EGFR exon 20 insertion mutation (Progression of disease on or after a platinum-based chemotherapy regimen)
    • Cohort B – HER2 activating mutation (Progression of disease on or after a platinum-based chemotherapy regimen)
    • Cohort C – NRG1 or ERBB family gene fusions (Progression of disease after standard of care)
  • Results: As of June 12, 2020, 23 pts (11 cohort A, 11 cohort B, 1 cohort C) were treated with tarloxotinib
    • Efficacy:

      Parameter

      Percentage

      Disease control rate

      60% (12/20 evaluable pts)

      Cohort A:

      Stable disease (SD)

      55% (6/11 pts)

      Progressive disease (PD)

      45% (5/11 pts)

      Cohort B:

      Tumor reduction by RECIST

      44% (4/9 evaluable pts)

      Partial response (PR)

      22% (2/9 pts)

      Stable disease (SD)

      44% (4/9 pts)

      Progressive disease (PD)

      33% (3/9 pts)

    • Three pts in cohort B were treated beyond 6 months with 3 pts still ongoing
    • Safety:
      • Most treatment-emergent adverse events (TEAEs) were grade 1/2. Those occurring at >20% were prolonged QTc (60.9%), rash (43.5%), nausea (21.7%), and diarrhea (21.7%)
      • The grade 3 TEAEs were prolonged QTc (34.8%), rash (4.3%), diarrhea (4.3%), and increased ALT (4.3%)
      • 5 of 23 (21.7%) pts required dose reduction and only 1/23 (4.3%) pts discontinued tarloxotinib due to a drug-related adverse event (infusion reaction)

Tarloxotinib (HAP – hypoxia-activated prodrug) shows first positive results in Phase 2 NSCLC with EGFR Exon 20 insertion/HER2 mutation

Share this

Facebook
fb-share-icon
Twitter
Tweet
LinkedIn
Share

CI Scientists Remarks: 

  • About the drug:
    • Hypoxia is important micro-environmental stress in solid tumors. Hypoxia leads to EGFR inhibitor resistance and causes poor prognosis in patients with solid tumors
    • Tarloxotinib is a hypoxia-activated prodrug (HAP) that releases a potent irreversible pan-ErbB TKI (tarloxotinib-E) under pathophysiological hypoxia present in solid tumors
    • Tarloxotinib is designed to increase therapeutic ratio over conventional EGFR-TKI therapy, thus inhibiting mutant forms of EGFR and HER2 with increased dose-intensity in hypoxic tumors
  • The failed initial trial in EGFR-mutant, T790M-negative NSCLC:
    • Initially, Threshold Pharmaceuticals (previous licensee of the drug) evaluated tarloxotinib in patients with EGFR-mutant, T790M-negative advanced NSCLC patients, where tarloxotinib failed to meet the primary endpoints
    • Discontinued investment in tarloxotinib program
  • Positive first results in NSCLC with EGFR Exon 20 insertion or HER2-activating mutations:
    • Rain Therapeutics (current developer of the drug) has initiated an open-label Phase 2 trial designed to evaluate the objective response rate of tarloxotinib administered once weekly by intravenous administration in NSCLC patients with EGFR Exon 20 insertion or HER2-activating mutations
    • The first results from the study reported that tarloxotinib exhibited antitumor activity in NSCLC pts with HER2 activating mutations. Also, the drug was well tolerated and exhibited low rates of severe EGFR-related toxicities such as rash and diarrhea

– Dr. Kowndinya, CI Scientists

For full story click here

Home