TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations

Inclusion Criteria

• Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) non-small cell lung cancer (NSCLC)
• Documented epithelial growth factor receptor (EGFR) in-frame exon 20 insertion mutation assessed by a clinical laboratory improvements amendment (CLIA)-certified (United States [US] sites) or an accredited (outside of the US) local laboratory The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations except EGFR mutations for which there are approved anti-EGFR TKIs (ie, exon 19 del, L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid)
• Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR exon 20 insertion mutation
• At least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version 1.1
• Life expectancy ≥3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Exclusion Criteria

• Received prior systemic treatment for locally advanced or metastatic disease
• Received radiotherapy ≤14 days before randomization or has not recovered from radiotherapy-related toxicities
• Received a moderate or strong cytochrome P-450 (CYP)3A inhibitor or moderate or strong CYP3A inducer within 10 days before randomization
• Have been diagnosed with another primary malignancy other than NSCLC
• Have current spinal cord compression or leptomeningeal disease
• Have uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure
• Received a live vaccine within 4 weeks before randomization per Summary of product characteristics (SmPCs) for pemetrexed, cisplatin, and carboplatin

The drug being tested in this study is called TAK-788. TAK-788 is being tested to evaluate

the efficacy as a first line treatment compare with platinum-based chemotherapy in the

participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose

tumors harbor EGFR exon 20 insertion mutations.

The study will enroll approximately 318 patients. Participants will be randomly assigned to

one of the two treatment groups-

- TAK-788 group (Arm A)

- Platinum-based chemotherapy group (Arm B)

The participants will be administered with TAK-788 orally in arm A and Pemetrexed/Cisplatin

or Pemetrexed/Carboplatin intravenously (IV) in arm B until the participants experience

progressive disease (PD) as assessed by blinded independent review committee (IRC),

intolerable toxicity or another discontinuation criteria. Participants in the chemotherapy

group may cross over to treatment with TAK-788 after IRC-assessed PD is documented.

Randomized treatment with TAK-788 or platinum-based chemotherapy may be continued after PD,

at the discretion of the investigator and with the sponsor's approval, if there is still

evidence of clinical benefit.

This multi-center trial will be conducted in United States, Europe, and Asia. The overall

time to participate in this study is until 3 years after the last participant is randomized.

Participants will make multiple visits to the clinic and will be followed for survival,

subsequent anticancer therapy, subsequent disease assessment outcome until disease

progression on a subsequent anticancer therapy, and participant-reported health status

(EQ-5D-5L) for 3 years after the last participant is randomized in the study and 30 days

after the last dose of study drug for safety follow-up.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Millennium Pharmaceuticals, Inc.

• Primary ID TAK-788-3001
• Secondary IDs NCI-2020-04004, NL20191212, 2019-001845-42, U1111-1232-6059
• Clinicaltrials.gov ID NCT04129502