Study Evaluating Zipalertinib with Chemotherapy for Lung Cancer Patients with Uncommon EGFR Mutations After Surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Taiho Oncology Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Nov 2025 → ongoing

Decision date (initial)

2025-10-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Taiho Oncology, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacogenetic, Safety

To compare the efficacy of zipalertinib combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in the study population

Conditions and MedDRA coding

Stage IB-IIIA NSCLC Patients with uncommon EGFR Mutations

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Provide written informed consent
2. ≥18 years of age (or meets the country’s regulatory definition for legal adult age, whichever is greater)
3. Histologically confirmed diagnosis of primary NSCLC on predominantly non-squamous histology
4. Documented EGFRmt status as determined by local testing performed at a clinical laboratory improvement amendments (CLIA) certified (US) or accredited (outside of the US) local laboratory, defined as either one of the following EGFRmt: a. exon20 insertion mutations or b. other uncommon, non-ex20ins EGFRmt (eg, G719X, L861Q, or S768I) Note: Participants may have “compound” EGFRmt as long as the above criteria are met (see Section 2.1. for details) and participants have no EGFRmt qualifying for osimertinib treatment).
5. MRI or CT scan of the brain done prior to surgery. Participants in whom this was not done prior to surgery may still be enrolled if appropriate imaging (ie, MRI or CT of the brain) is performed prior to randomization.
6. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumor. Resection may be accomplished by open thoracotomy or Video Associated Thoracic Surgery (VATS) techniques.
7. Classified post-operatively as either Stage IB, IIA, IIB, or IIIA according to the TNM staging system for lung cancer (AJCC 9th edition).
8. Complete recovery from surgery at the time of randomization. Treatment cannot commence within 4 weeks following surgery, but no more than 10 weeks may have elapsed between surgery and randomization. Complete post-operative wound healing must have occurred following any surgery.
9. Eastern Cooperative Oncology Group Performance Status of (ECOG PS) 0 or 1.
10. Adequate organ function, as defined: Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 × 109/L); Platelets ≥100,000/mm3 (≥100 × 109/L) without platelet transfusion within the last 14 days prior first dose of study treatment; Hemoglobin ≥9.0 g/dL without blood transfusion within 14 days prior first dose of study treatment; Creatinine Clearance ≥50 mL/min (measured or calculated by Cockcroft and Gault equation); Prothrombin Time (PT) ≤1.5 × upper limit of normal (ULN) unless the participant is receiving anticoagulant therapy; Activated Partial Thromboplastin Time (aPTT) OR Partial Thromboplastin Time (PTT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy; Serum total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN or ≤3.0 × ULN for participants with documented Gilbert’s syndrome (unconjugated hyperbilirubinemia); Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 × ULN
11. Women of child-bearing potential (WOCBP) must have a negative blood-based pregnancy test) within 7 days prior to first dose. Female participants are not considered to be of childbearing potential if they are permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or are postmenopausal (no menses for 12 months without an alternative medical cause).
12. Both males and females of reproductive potential must agree to use effective birth control during the study starting prior to the first dose of study treatment and for 1 month after the last dose of zipalertinib/placebo, 6 months after the last dose of chemotherapy, or longer based on local requirements
13. Archival tumor tissue available for submission, with minimum quantity sufficient to evaluate EGFRmt status and, where possible, other biomarkers. Participants with insufficient tissue (details provided in laboratory manual) may be eligible following discussion with the Sponsor.

Exclusion criteria 13

1. If patient currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study.
2. Treatment with any of the following within the time frame specified: a. Zipalertinib (TAS6417/CLN-081) or any other EGFR inhibitor at any time b. Pre-operative or post-operative or planned radiation therapy for the current lung cancer c. ny prior systemic anticancer therapy (eg, neoadjuvant chemotherapy), including investigational therapy, for treatment of NSCLC d. Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks of the first dose of study treatment e. All prescribed medication, over-the-counter medication, vitamin preparations and other food supplements, or herbal medications that are strong or moderate cytochrome p450 (CYP) 3A4 inducers or inhibitors within 7 days prior to first dose. f. Treatment with an investigational drug within five half-lives of the compound or any of its related material, if known.
3. Has received only segmentectomies or wedge resections
4. Past medical history of ILD/pneumonitis, drug-induced ILD/pneumonitis or any evidence of clinically active ILD/pneumonitis.
5. Impaired cardiac function or clinically significant cardiac disease, including any of the following: a. History of congestive heart failure (CHF) Class III/IV according to the New York b.Serious cardiac arrhythmias requiring treatment c.Mean resting corrected QT interval (QTc) >470 msec obtained from 3 ECGs using Fridericia’s formula (QTcF). d. Any factors that significantly increase the risk of QTc prolongation or risk of arrhythmic events such as congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
6. Unable to swallow tablets or has any disease or condition that may significantly affect gastrointestinal (GI) absorption of zipalertinib (such as inflammatory bowel disease, malabsorption syndrome, or prior significant bowel resection).
7. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), with no evidence of disease for >5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.
8. Known history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) that is unstable or not controlled with treatment. Screening not required
9. Active bleeding disorders.
10. Known: a. Hypersensitivity: i. To the ingredients in zipalertinib/placebo or any drugs similar in structure or class. ii. To platinum-containing drugs (ie, cisplatin, carboplatin), pemetrexed, or any known excipients of these drugs. b. Contraindications to platinum-containing drugs (ie, cisplatin, carboplatin) or pemetrexed according to the respective local labels. 11. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed. 12. Is pregnant or lactating or planning to become pregnant. 13. Judgment by the investigator that the individual should not participate in the study if the individual is unlikely b. Contraindications to platinum-containing drugs (ie, cisplatin, carboplatin) or pemetrexed according to the respective local labels.
11. Is unable or unwilling to take dexamethasone, folic acid, and/or vitamin B12 supplementation during treatment with pemetrexed.
12. Is pregnant or lactating or planning to become pregnant.
13. Judgment by the investigator that the individual should not participate in the study if the individual is unlikely to comply with study procedures, restrictions, and requirements

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free survival (DFS) by investigator assessment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Taiho Oncology Inc.

Sponsor organisation

Taiho Oncology Inc.

Address

101 Carnegie Center Suite 300

City

Princeton

Postcode

08540-6231

Country

United States

Scientific contact point

Organisation

Taiho Oncology Inc.

Contact name

Medical Information

Public contact point

Organisation

Taiho Oncology Inc.

Contact name

Medical Information

Third parties 11

Locations

9 EU/EEA countries · 86 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 7 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 104 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications