EGFR Exon 20 NSCLC - October 2020

EGFR Exon 20 NSCLC - October 2020

Positive interim data from Phase 1/2a study of CLN-081 in patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations reported

17 Sep 2020

CLN-081 (TAS6417; Pan-mutation–selective EGFR tyrosine kinase inhibitor) – Taiho/ Cullinan Pearl – subsidiary of Cullinan Oncology

  • Phase 1/2a open-label, multi-center study of CLN-081 in NSCLC pts harboring EGFR exon 20 insertion mutations at ESMO2020
  • Results: As of Sep 1, 2020, 22 pts dosed twice daily with CLN-081 at dose levels ranging from 30-150 mg. 17 patients were evaluated for RECIST 1.1 response
    • Efficacy:
      • Objective responses (all PRs) were observed in 6 of 17 (35 %) response evaluable patients; two patients with confirmed partial response, three patients with ongoing PR, and one with an unconfirmed PR
      • Stable disease (SD) was observed in 11 patients with the change in target lesions ranged from +3% to -21%, of which 9 patients remained on treatment with stable disease

        Response characteristics

        N=17

        Best response

        Progressive disease (PD), n (%)

        0 (0%)

        Stable disease (SD), n (%)

        11 (65%)

        Partial response (PR), n (%)

        6* (35%)

        Complete response (CR), n (%)

        0 (0%)

        Confirmed response, n

        2

        Unconfirmed response, n

        1

        Pending confirmation, n

        3*

        *one additional PR achieved after 01 Sep data cut

    • Safety:
      • Most treatment-emergent adverse events (TEAEs) were rashes and dry skin, with only one case of grade 1 drug-related diarrhea
      • No dose-limiting toxicities, grade 3 diarrhea, or grade 3 rash were reported

Cullinan Pearl’s CLN-081 Pan-mut–selective EGFR TKI shows positive interim results (Phase 1/2) in NSCLC with EGFR Exon 20 insertion mutations

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CI Scientists Remarks: 

  • Rationale for development:
    • With several drugs targeting EGFR Exon 20 are in development, preliminary reports suggest that WT EGFR-related adverse events are common and may limit the efficacy and durability of responses
    • CLN-081 is a potent inhibitor of Exon 20 mutations with a broad spectrum of EGFR-mutant activity but also shows selectivity over WT EGFR suggesting a potentially wider clinical therapeutic window than most approved/in-development EGFR TKIs
  • Preclinical data:
    • In cell lines for Exon 20 mutations, selectivity indexes (WT EGFR/mutant EGFR ratio of inhibition) favored CLN081 over poziotinib and osimertinib, suggestive of a wider therapeutic window
    • CLN-081 is also active against Exon19del, L858R, and T790M, as well as less common G719X, L861Q and S768I mutations
  • Cullinan licensed CLN-081 from Taiho Pharmaceutical. Under the terms of the agreement, Cullinan received the global rights (ex-Japan) to develop and commercialize CLN-081
  • Dose escalation in this trial is ongoing and Phase 1 expansion has been initiated. Cullinan is planning to discuss the further clinical pathway with regulatory bodies

– Dr. Kowndinya, CI Scientists

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