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    DRUG:

    zipalertinib (CLN-081)

    i
    Other names: CLN-081, TAS6417, TPC-064, CLN 081, CLN081, TAS 6417, TAS-6417, TPC064, TPC 064
    Company:
    Cullinan Therap, Otsuka, ZAI Lab
    Drug class:
    EGFR inhibitor, Tyrosine kinase inhibitor
    Related drugs:
    18d
    REZILIENT2: A Study of Zipalertinib in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions or Other Uncommon Mutation. (clinicaltrials.gov)
    P2, N=220, Recruiting, Taiho Oncology, Inc. | N=324 --> 220
    Enrollment change
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    zipalertinib (CLN-081)
    18d
    REZILIENT3 (REsearching ZIpaLertinib In Egfr Non-small Cell Lung Cancer Tumors) (clinicaltrials.gov)
    P3, N=285, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    carboplatin • zipalertinib (CLN-081)
    1m
    TAS6417-302: Study Evaluating Zipalertinib with Chemotherapy for Lung Cancer Patients with Uncommon EGFR Mutations After Surgery (2025-521775-31-00)
    P2/3, N=131, Recruiting, Taiho Oncology Inc.
    New P2/3 trial
    |
    EGFR mutation • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 20 mutation
    |
    cisplatin • carboplatin • pemetrexed • zipalertinib (CLN-081)
    2ms
    REZILIENT2: A Study of Zipalertinib in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions or Other Uncommon Mutation. (clinicaltrials.gov)
    P2, N=324, Recruiting, Taiho Oncology, Inc. | N=224 --> 324 | Trial completion date: Aug 2026 --> Dec 2028 | Trial primary completion date: Feb 2026 --> Aug 2028
    Enrollment change • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    zipalertinib (CLN-081)
    2ms
    Zipalertinib With Carboplatin and Pemetrexed for the Treatment of Resectable, Stage II-IIIB, Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=16, Not yet recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Dec 2029 --> Jun 2030 | Initiation date: Jan 2026 --> Jun 2027 | Trial primary completion date: Dec 2028 --> Jun 2029
    Trial completion date • Trial initiation date • Trial primary completion date
    |
    EGFR mutation • EGFR L861Q • EGFR G719X
    |
    carboplatin • pemetrexed • zipalertinib (CLN-081)
    2ms
    Zipalertinib-A Novel Treatment Opportunity for Non-Small Cell Lung Cancers with Exon 20 Insertions and Uncommon EGFR Mutations. (PubMed, Cancers (Basel))
    The role and the integration of therapies targeting exon20ins or uncommon mutations into the first- and second-line treatment armamentarium for NSCLC patients is not yet fully established, and the therapeutic impact of monotherapies (e.g., sunvozertinib, firmonertinib) versus combinations with standard platinum-based chemotherapy (e.g., zipalertinib, amivantamab) currently still lacks robust evidence to further change the therapeutic landscape for these patients. Therefore, results from the ongoing trials are eagerly awaited and are expected to shed some light on these open questions.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Ivesa (firmonertinib) • Zegfrovy (sunvozertinib) • zipalertinib (CLN-081)
    4ms
    Zipalertinib With Carboplatin and Pemetrexed for the Treatment of Resectable, Stage II-IIIB, Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=16, Not yet recruiting, Jonsson Comprehensive Cancer Center
    New P2 trial
    |
    carboplatin • pemetrexed • zipalertinib (CLN-081)
    5ms
    REZILIENT3 (REsearching ZIpaLertinib In Egfr Non-small Cell Lung Cancer Tumors) (clinicaltrials.gov)
    P3, N=272, Recruiting, Taiho Oncology, Inc. | Trial completion date: Aug 2026 --> May 2027 | Trial primary completion date: Jul 2026 --> Oct 2026
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation
    |
    carboplatin • zipalertinib (CLN-081)
    6ms
    Poziotinib for EGFR exon 20-insertion NSCLC: Clinical efficacy of the phase 2 ZENITH trial and differential impact of EGFR exon 20 insertion location on sensitivity. (PubMed, Nat Commun)
    In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. In comparison, in the previously published EXCLAIM trial (NCT02716116), mobocertinib demonstrates similar activities across both groups in tumor size reduction (-38.5% vs. -34.1%, p = 0.59) and PFS (12.0 vs. 13.0 months, p = 0.99). Therefore, EGFRex20ins location differentially impacts the sensitivity of TKIs.
    P2 data • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Gilotrif (afatinib) • Pozenveo (poziotinib) • Exkivity (mobocertinib) • zipalertinib (CLN-081)
    6ms
    REZILIENT4: A Study to Assess the Efficacy and Safety of Zipalertinib Versus Placebo for Adjuvant Treatment in Participants With Stage IB-IIIA NSCLC With Uncommon EGFR Mutations, Following Complete Tumor Resection (clinicaltrials.gov)
    P3, N=360, Recruiting, Taiho Oncology, Inc.
    New P3 trial
    |
    cisplatin • carboplatin • pemetrexed • zipalertinib (CLN-081)
    10ms
    REZILIENT2: A Study of Zipalertinib in Patients With Advanced Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions or Other Uncommon Mutation. (clinicaltrials.gov)
    P2, N=220, Recruiting, Taiho Oncology, Inc. | N=160 --> 220
    Enrollment change
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation
    |
    zipalertinib (CLN-081)
    10ms
    Zipalertinib in Patients With EGFR Exon 20 Insertion-Positive NSCLC Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab. (PubMed, J Clin Oncol)
    Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC who received prior platinum-based chemotherapy with or without amivantamab.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Rybrevant (amivantamab-vmjw) • zipalertinib (CLN-081)