A Study of Amivantamab and Lazertinib in Combination with Platinum-Based Chemotherapy Compared with Platinum-Based Chemotherapy in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure

JRCT ID: jRCT2031210358

Registered date:01/10/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Carcinoma, Non-Small-Cell Lung
• Date of first enrollment: 06/12/2021
• Target sample size: 600
• Countries of recruitment: United States Of America,Japan,Argentina,Japan,Belgium,Japan,Brazil,Japan,Bulgaria,Japan,Canada,Japan,China,Japan,Czechia,Japan,Germany,Japan,India,Japan,Israel,Japan,Korea,Japan,Malaysia,Japan,Mexico,Japan,Netherlands,Japan,Poland,Japan,Sweden,Japan,Taiwan,Japan,Turkey,Japan,Denmark,Japan,Spain,Japan,France,Japan,Un Of Great Britain And Northern Ireland,Japan,Hong Kong,Japan,Italy,Japan,Portugal,Japan,Russian Federation,Japan
• Study type: Interventional

Intervention(s)

Lazertinib (JNJ-73841937, YH-25448) : Lazertinib will be administered orally.
Amivantamab (JNJ-61186372) : Amivantamab will be administered as an IV infusion.
Pemetrexed : Pemetrexed will be administered as an IV infusion.
Carboplatin : Carboplatin will be administered as an IV infusion.

Arm A: LACP/ACP-L
LACP dosing (from study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.

Arm B: CP (Carboplatin and Pemetrexed)
Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.

Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)
Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.

Arm A2 (Extension Cohort): ACP-L
Participants will receive Amivantamab and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.

Arm C2 (Extension Cohort): ACP
Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.

Outcome(s)

Primary Outcome

Progression-Free Survival (PFS) According to RECIST v1.1 Guidelines as Assessed by Blinded Independent Central Review (BICR)
PFS is defined as the time from randomization until the date of objective disease progression or death, whichever comes first, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome

Objective Response as Assessed by BICR
Objective response is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as their best response as defined by BICR using RECIST v1.1 criteria.

Overall Survival (OS)
Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.

Duration of Response (DoR)
DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR.

Time to Subsequent Therapy (TTST)
TTST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death whichever comes first.

Progression-Free Survival After First Subsequent Therapy (PFS2)
PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.

Time to Symptomatic Progression (TTSP)
TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms.

Intracranial PFS
Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1.

Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Number of Participants with Clinical Laboratory Abnormalities
Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urinalysis) will be reported.

Serum Concentration of Amivantamab
Serum samples will be analyzed to determine concentrations of amivantamab.

Plasma Concentration of Lazertinib
Plasma samples will be analyzed to determine concentrations of lazertinib.

Number of Participants with Anti-Amivantamab Antibodies
Number of participants with anti-amivantamab antibodies will be reported.

Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)
NSCLC-SAQ is a 7-item PRO measure designed for use in adults to assess symptoms of advanced non-small cell lung cancer (NSCLC). The NSCLC-SAQ has a seven-day recall period. It contains five domains and accompanying items that will be identified as symptoms of NSCLC: cough (1 item), pain (2 items), dyspnea (1 item), fatigue (2 items), and appetite (1 item). Each item uses a response scale between 0 to 4, with higher scores indicating more severe symptomatology. All five of these domains must be non-missing to compute a total score, with a response range from 0 to 20 with higher scores indicating more severe symptomatology.

European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Score
The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.

Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)
PROMIS-PF is used to characterize and better understand overall health, level of physical disability, and general well-being. Physical function is a foundation for commonly used general and cancer-specific patient reported outcomes (PRO) measures.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated
- Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after the timne of locally advanced or metastatic disease diagnosis by either epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation
- A participant with a history of brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization and the participant can be receiving no greater than10 milligrams (mg) prednisone or equivalent daily for the treatment of intracranial disease
- Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <= 2 peripheral neuropathy, or Grade <= 2 hypothyroidism stable on hormone replacement)
- A woman of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
- Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second- line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Participants who received either neoadjuvant and/or adjuvant treatment of any type are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting. Treatment with osimertinib must be discontinued at least 8 days (4 half-lives) prior to randomization (that is last dose no later than Day -8)

Exclude criteria

- Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization
- Participant with symptomatic or progressive brain metastases
- Participant has history of or current evidence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
- Participant has known small cell transformation
- Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
- Participant has a history of clinically significant cardiovascular disease including, but not limited to diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to randomization; myocardial infarction; unstable angina; stroke; transient ischemic attack; coronary/peripheral artery bypass graft; or acute coronary syndrome. Participant has a significant genetic predisposition to venous thromboembolic events. Participant has a prior history of venous thromboembolic events and is not on appropriate therapeutic anticoagulation as per National Comprehensive Cancer Network or local guidelines

Related Information

• Primary Sponsor: Nakama Takahiro
• Secondary ID(s): NCT04988295