zipalertinib (CLN-081) / Cullinan Therap, Otsuka, ZAI Lab - LARVOL DELTA

Zipalertinib in Patients With EGFR Exon 20 Insertion-Positive NSCLC Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab. (PubMed, J Clin Oncol) - P1/2 | "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 • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • EGFR

Activity of zipalertinib against active central nervous system (CNS) metastases in patients with non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins)/other uncommon mutations (ESMO 2025) - P2 | "Conclusions In summary, zipalertinib demonstrated clinically meaningful intracranial antitumor activity in patients with NSCLC harboring ex20ins/other uncommon EGFR mt, similar to the overall systemic anticancer activity in this population, with no new safety signals observed. Cohort enrollment is ongoing to better characterize clinical activity of zipalertinib against CNS lesions."

Clinical • EGFR exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Clinical outcomes and molecular characterization of patients with uncommon EGFR-mutated NSCLC: A single-centre study (ELCC 2026) - "MPFS for osimertinib (osi) or lazertinib (lazer) monotherapy (n=27), osi + chemotherapy (n=4) and afatinib (n=3) were 10.0 mo (95% CI 6.2–30.3), 9.0 mo (95% CI 4.2–NR) and 16.7 mo (95% CI 12.9–NR), respectively. MPFS was not reached with amivantamab + lazer (n=3), chemotherapy ± immunotherapy (n=6) and zipalertinib (n=1). Progression occurred at 1.5 mo in one patient treated with sunvozertinib.Conclusions This real-world cohort provides broad clinical and molecular characterization of uncommon EGFR-mutated NSCLC and supports the need for dedicated prospective trials."

Clinical • Clinical data • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Enhanced antitumor activity of zipalertinib and amivantamab combination in EGFR mutant NSCLC models (AACR 2026) - "These results provide mechanistic insights into the observed combinatorial efficacy of zipalertinib and amivantamab, both in vitro and in vivo. Further, our findings support the therapeutic potential of zipalertinib and amivantamab in EGFR-mutant NSCLC and further clinical investigations."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Zipalertinib in NSCLC Patients (Pts) With EGFR Exon 20 Insertion (Ex20Ins) Mutations Who Received Prior Amivantamab (IASLC-WCLC 2025) - "Mature efficacy data, including at least 9 months follow up for all 83 pts will be presented. Conclusions : Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in pts with exon20ins NSCLC who have received prior chemotherapy and prior amivantamab, reflecting a clinically-relevant patient population for which there are currently no approved therapies."

Clinical • EGFR exon 20 • Anemia • Dental Disorders • Dermatitis • Dermatology • Hematological Disorders • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Pneumonia • Pruritus • Solid Tumor • Stomatitis • EGFR

Phase 2 Interim Results of Zipalertinib in Patients With NSCLC Harboring Uncommon Non-Exon 20 Insertion EGFR Mutations (IASLC-WCLC 2025) - P2 | "The safety profile of zipalertinib was manageable, with no new safety signals. Enrollment in this study is ongoing, focusing on previously untreated patients to confirm the observed preliminary clinical efficacy."

Clinical • P2 data • Anemia • Dental Disorders • Dermatitis • Dermatology • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Stomatitis • EGFR

EGFR and MET mRNA overexpression in non-small cell lung cancer: Prevalence and sensitivity to targeted therapies (ESMO-TAT 2026) - "MET-overexpressing models were highly sensitive to MET inhibition by tepotinib and capmatinib, with approximately 70% reduction in viability at <0.1 μM concentration, and one model showed sensitivity to the telisotuzumab vedotin, a MET ADC. The EGFR-overexpressing model exhibited strong sensitivity to afatinib and zipalertinib, whereas the anti-EGFR antibody cetuximab induced limited growth inhibition. mRNA overexpression of MET and EGFR identifies a small subset of NSCLC patients which may represent potential candidates for targeted treatment. mRNA overexpression of MET and EGFR identifies a small subset of NSCLC patients which may represent potential candidates for targeted treatment. Patient-derived 3D cultures confirmed that MET-overexpressing models are sensitive to MET inhibitors and to telisotuzumab-vedotin, while EGFR-overexpressing models show sensitivity to EGFR TKIs and limited response to the anti-EGFR antibody cetuximab. These findings support the..."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Efficacy of zipalertinib in NSCLC patients with EGFR exon 20 insertion mutations who received prior platinum-based chemotherapy with or without amivantamab. (ASCO 2025) - P1/2 | "Of the 51 pts with prior ami, 30 had no other ex20ins-directed therapy, while 21 had also received other ex20ins drugs (such as mobocertinib, sunvozertinib, BLU-451, or poziotinib), the cORR was 30.0% and 14.3%, respectively. Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in pts with exon20ins NSCLC who have received prior platinum-based chemotherapy and for those who received prior amivantamab, a significant and growing unmet need. BICR assessed tumor responses per RECIST v1.1.CR=complete response, PR=partial response, SD=stable disease."

Clinical • EGFR exon 20 • IO biomarker • Anemia • Dental Disorders • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

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 | Sponsor: Taiho Oncology, Inc. | N=324 ➔ 220

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

REZILIENT3 (REsearching ZIpaLertinib In Egfr Non-small Cell Lung Cancer Tumors) (clinicaltrials.gov) - P3 | N=285 | Active, not recruiting | Sponsor: Taiho Oncology, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

TAS6417-302: Study Evaluating Zipalertinib with Chemotherapy for Lung Cancer Patients with Uncommon EGFR Mutations After Surgery (clinicaltrialsregister.eu) - P2/3 | N=131 | Recruiting | Sponsor: Taiho Oncology Inc.

New P2/3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

In February, Taiho completed enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC (GlobeNewswire) - "Taiho expects to obtain top-line results by the end of 2026."

EGFR exon 20 • Enrollment closed • P3 data: top line • Non Small Cell Lung Cancer

Portfolio Highlights:…Zipalertinib (EGFR ex20ins inhibitor) (GlobeNewswire) - "In February, Taiho completed the rolling NDA submission to the U.S. FDA seeking accelerated approval of zipalertinib for the treatment of patients with locally advanced or metastatic EGFR ex20ins NSCLC who have previously received platinum-based systemic chemotherapy."

EGFR exon 20 • FDA filing • Non Small Cell Lung Cancer

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 | Sponsor: 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 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

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 | Sponsor: 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 • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

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."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Phase (Ph) 1/2a study of CLN-081 in patients (pts) with NSCLC with EGFR exon 20 insertion mutations (Ins20). (ASCO 2022) - P1/2 | "In pts with heavily-pretreated advanced EGFR ins20 NSCLC, CLN-081 has a manageable safety profile, with anti-tumor activity across the range of doses tested. Further, CLN-081 has demonstrated a favorable clinical profile at the dose of 100 mg BID, with an encouraging objective response rate, response durability, and no Gr 3 rash or diarrhea."

Clinical • EGFR exon 20 • Anemia • Fatigue • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Safety, Tolerability, and Antitumor Activity of Zipalertinib Among Patients With Non-Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 20 Insertions. (PubMed, J Clin Oncol) - "Zipalertinib has encouraging preliminary antitumor activity in heavily pretreated patients with EGFR ex20ins-mutant NSCLC, with an acceptable safety profile, including low frequency of high-grade diarrhea and rash."

EGFR exon 20 • Journal • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Safety and anti-tumour activity of zipalertinib in NSCLC patients (pts) with EGFR exon 20 insertion (ex20ins) mutations who received prior amivantamab (ESMO 2024) - P1/2 | "This is the first report to systematically characterize the anti-tumor activity of a new irreversible and selective EGFR ex20ins TKI, in heavily treated pts with NSCLC harboring EGFR ex20ins mutations who have received prior amivantamab. In this amivantamab resistant setting, zipalertinib demonstrated promising efficacy, similar to pts that progressed after platinum-based chemotherapy alone and had a manageable safety profile."

Clinical • EGFR exon 20 • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Zipalertinib (EGFR ex20ins inhibitor), collaboration with Taiho Oncology: EGFR ex20ins NSCLC (The Manila Times) - "Taiho expects completion of the NDA submission in Q1 2026; Taiho expects to complete enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC in H1 2026; Cullinan is eligible to receive up to $130 million in payments for U.S. regulatory milestones and a 50/50 profit share in the U.S."

EGFR exon 20 • Enrollment status • FDA filing • Financing • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

Efficacy of zipalertinib in Asian patients with EGFR exon 20 insertion mutated (Ex20ins) advanced non-small cell lung cancer (NSCLC) (ESMO Asia 2025) - P3 | "Here we report on the efficacy and safety of zipalertinib in pts from Asia vs the rest of world (ROW). Pts who have progressed on chemotherapy with or without prior amivantamab (including those with amivantamab and other ex20ins target therapy, such as mobocertinib) were treated with zipalertinib at 100 mg oral twice daily. Zipalertinib demonstrated similarly meaningful clinical benefit in pts from Asia and ROW. Zipalertinib was likewise tolerable and demonstrated a manageable safety profile in both groups."

Clinical • EGFR exon 20 • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Taiho Oncology, Taiho Pharmaceutical and Cullinan Therapeutics Initiate Rolling Submission of New Drug Application to U.S. Food and Drug Administration for Zipalertinib for Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations (PRNewswire) - "The NDA submission is based on the primary efficacy data from the REZILIENT1 trial..."

EGFR exon 20 • FDA filing • Non Small Cell Lung Cancer

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 | Sponsor: Jonsson Comprehensive Cancer Center

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

REZILIENT3 (REsearching ZIpaLertinib In Egfr Non-small Cell Lung Cancer Tumors) (clinicaltrials.gov) - P3 | N=272 | Recruiting | Sponsor: 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 • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Zipalertinib: Regulatory filing in US for NSCLC in FY 2025 (Otsuka) - Q3 FY2025 Results

FDA filing • Lung Cancer • Non Small Cell Lung Cancer • Oncology