A Phase 1/2 Study of Necitumumab plus Osimertinib for Advanced Non-small Cell Lung Cancer with EGFR-mutation

JRCT ID: jRCT2021210079

Registered date:31/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-small Cell Lung Cancer with EGFR-mutation
• Date of first enrollment: 16/09/2022
• Target sample size: 92
• Study type: Interventional

Intervention(s)

<Phase I>
Osimertinib 80 mg is orally administered once daily for 4 weeks, and necitumumab (dose level of necitumumab is 600 mg or 800 mg) is administered on Day 1 and Day 15.
<Phase II>
Osimertinib 80 mg is orally administered once daily for 4 weeks, and necitumumab (the dose level of necitumumab is the RD determined in Phase I) is a dministered on Day 1 and Day 15 until the drugs used in the Clinical Trial discontinuation criteria are met.

Outcome(s)

Primary Outcome

<Phase I>
Dose-limiting toxicity
Determination of maximum tolerated dose
Recommended dose
<Phase II>
Objective Response Rate

Secondary Outcome

<Phase I>
1)Safety (proportion of patients discontinuing protocol treatment due to toxicity, incidence of adverse events, and their severity)
2) Efficacy (evaluable cases)
<Phase II>
1) Objective Response Rate*1
2) Disease Control Rate*1
3) Progression-Free Survival*1
4) Overall Survival
5) Safety*2 (proportion of patients discontinuing protocol treatment due to toxicity, incidence of adverse events, and their severity)
*1 based on RECIST Ver 1.1.
*2 According to CTCAE Ver. 5.0

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1)A histologically or cytologically confirmed diagnosis of non-small-cell lung cancer
(2) Have clinical stage IIIB, IIIC, IVA, IVB that cannot be treated with radical radiotherapy and surgery or postoperative recurrent cases
*Practice for Lung Cancer (January 2017 [8th edition]). Japanese Lung Cancer Society/Edition
(3)An observed EGFR (Exon 19 deletion or Exon 21 L858R mutation) (However, mergers with uncommon mutations can be registered)
(4)With measurable lesions based on RECIST Ver 1.1. (Not required for Phase I)
(5)With no history of chemotherapy treatment for non-small-cell lung cancer (Preoperative and postoperative adjuvant chemotherapy, excluding EGFR inhibitors, is acceptable if 6 months have passed since the last dose. Pleurodesis is acceptable.)
(6)Aged >=20, at the time of consent
(7)ECOG PS 0-1
(8)Main organ functions must meet the following criteria within 14 days prior to enrollment. If there are multiple test results within this period, then the most recent test prior to enrollment will be adopted.
For measurement, should not do transfuse or administer hematopoietic factor preparations within 14 days before the test.
1)neutrophil >=1,500/mm3
2)hemoglobin >=9.0g/dL
3)platelet >=100,000/mm3
4)AST <=100 IU/L (with lung metastasis, <=200 IU/L)
5)ALT <=100 IU/L (with lung metastasis, <=200 IU/L)
6)bilirubin <=1.5mg/dL (with lung metastasis, <=3.0mg/dL)
7)serum creatinine >=45 ml/min
8) SpO2 >=93%
(9)Written informed consent

Exclude criteria

(1)Have active interstitial lung disease, or a history of drug-induced pneumonitis, radiation pneumonitis needing steroid treatment.
(2)No major surgery within 4 weeks before registration
(3)With brain metastasis or spinal cord compression that is not clinically stable. However, patients who do not require steroids and are neurologically stable for at least 2 weeks after completion of definitive and steroid therapy will not be excluded.
(4)Currently have serious complications including uncontrolled heart, lung, liver, and renal disease.
(5)Receiving steroids more than 4 weeks (10mg prednisolone equivalent or more) or immunosuppressants
(6) Cases that meet any of the following heart-related criteria
1)With resting correction QT interval (QTcF) greater than 470 msec
2)Have severe coronary disease, uncontrollable congestive heart failure (NYHA III or IV), or uncontrollable arrhythmia, uncontrollable hypertension despite antihypertensive treatment (Systolic pressure =>150 mmHg or diastolic pressure =>90 mmHg)
(7)With or a history of thromboembolic disease
(8)With active hepatitis B and C (HBsAg positive, HBs antibody positive, HBc antibody positive, HBV DNA should be measured. HBV DNA positive is excluded.)
(9)Women who are currently pregnant or breastfeeding. If breastfeeding is discontinued before participation in the study, lactation should be discontinued during the study period and at least 30 days after the end of drugs used in the Clinical Trial administration.
(10)With intractable nausea and vomiting, chronic gastrointestinal disease, dysphagia of the preparation, total gastrectomy and serious bowel resection that prevents adequate absorption of osimertinib
(11)Have pleural effusion, ascites or pericardial effusion that require drainage
(However, cases in which pleural effusion is controlled for 2 weeks before enrollment by drainage or pleurodesis are not excluded.)
(12)Have contraindication to osimertinib and necitumumab.
(13)Have complications with double cancers that have a disease-free period of less than 5 years (enrollment is permitted if intraepithelial carcinoma and intramucosal carcinoma lesions have been judged as cured from localized treatment regardless of the disease-free period).
(14)Impossible to take drugs orally
(15)With a history of hypersensitivity to osimertinib (or drugs of the same chemical structure or class as osimertinib) or necitumumab or vehicle for these drugs.
(16)Patients whose participation in the trial is judged to be inappropriate by the doctor

Related Information

• Primary Sponsor: Maemondo Makoto
• Source(s) of Monetary Support: Nippon Kayaku Co.,Ltd.