A Phase I/II Study of necitumumab + carboplatin + nab-paclitaxel + pembrolizumab for previously untreated advanced squamous non-small cell lung cancer study

JRCT ID: jRCT2031210387

Registered date:22/10/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: squamous non-small cell lung cancer(SqCLC)
• Date of first enrollment: 04/08/2022
• Target sample size: 60
• Study type: Interventional

Intervention(s)

Phase 1; In combination with carboplatin, nab-paclitaxel and pembrolizumab used in routine practice as induction therapy, the investigational product (necitumumab) will be infused intravenously at 400mg in Level 1, 600mg in Level 2, and 800mg in Level 3 according to the escalation scheme.
In combination with pembrolizumab as maintenance therapy, the final dose level of induction therapy with the investigational product (necitumumab) will be infused intravenously.
Phase II study: The recommended phase I dose of the investigational product (necitumumab) is infused in combination with carboplatin, nab-paclitaxel and pembrolizumab used in routine practice as induction therapy.
In combination with pembrolizumab as maintenance therapy, the recommended phase 1 dose of the investigational product (necitumumab) will be infused intravenously.

Outcome(s)

• Primary Outcome: Phase1:Determination of maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and recommended dose (RD). Phase2:Response rates (ORR: Objective Response Rate).

Secondary Outcome

Phase1
1)Safety (rate of discontinuation of protocol treatment due to toxicity, incidence of adverse events, and severity)
*By CTCAE v5.0-JCOG
2)Response rate (ORR:Objective Response Rate) (evaluable cases)
*Be based on RECIST version 1.1
3)Survival time (Overall Survival) (evaluable cases)
4)24-week survivorship (24 weeks Survival Rate) (evaluable cases).
Phase2
1)Disease-control rate (DCR:Disease Control Rate).
2)Progression-free survival (PFS:Progression-Free Survival).
3)Survival time (Overall Survival).
4)Two-year survivorship (2 years Survival Rate).
5)Safety (proportion of patients discontinuing protocol treatment due to toxicity, incidence of adverse events, and their severity)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

(1)Lung squamous cell carcinoma confirmed by histology or cytology
(2)Patients with Clinical Stage 3B, 3C or 4A-4B/Postoperative Recurrent Cases Unamenable to Radical Radiation
*Practice for Lung Cancer (January 2017 [8th edition]). Japanese Lung Cancer Society/Edition
(3)Patients with measurable lesions based on RECISTVer 1.1.
*It is not mandatory in phase 1 trials.
(4)Patients with no history of chemotherapy treatment for squamous cell carcinoma of the lung using cytotoxic anticancer agents or agents with EGFR inhibitory activity, or treatment with immune checkpoint inhibitors
*Preoperative and postoperative adjuvant chemotherapy, excluding EGFR inhibitors, is acceptable if 6 months have passed since the last dose.
*Pleurodesis is acceptable.
(5)Patients aged 20 years and younger than 80 years at the time of informed consent
(6)Patients with an ECOG performance status (PS) between 0 and 1.
(7)Patients who meet the following criteria for major organ function within 14 days before enrollment (the same day of the week before 2 is allowed based on the date of enrollment)
In addition, if more than one test result exists within this period, the most recent one to be registered shall be adopted, and in addition, it shall be verified that blood transfusion and hematopoietic factor products, etc. have not been administered within 14 days before the test day.
1)Neutrophil count: 1500/microL or higher
2)Hemoglobin: 10.0g/dL or higher
3)Platelet count: 100,000/mm3 or higher
4)AST: 100U/L or less or 2.5 times or less the upper limit of the institutional standard value (5 times or less if the patient has liver metastasis)
5)ALT: 100U/L or less or 2.5 times or less the upper limit of the institutional standard (5 times or less if liver metastasis is present)
6)Total bilirubin: 1.5mg/dl or less or 1.5 times or less the upper limit of the institutional standard
(3 times or less if liver metastasis or Gilbert's syndrome is present)
7)Serum creatinine clearance: 45 ml/min (calculated) or more
8)SpO2>=93 %
(8)Patients who have been fully explained about the contents of the study and have given their written consent.

Exclude criteria

(1)Patients with interstitial lung diseases (ILDs), drug-induced ILDs, a history of radiation pneumonitis requiring steroidal treatment, or active ILD.
(2)Patients 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.
(3)Patients who have received radiation to the primary lesion or the evaluated lesion.
*Patients will not be excluded if they have received palliative irradiation for the primary lesion or for lesions other than the evaluated lesion for at least 2 weeks.
(4)Patients with serious complications (uncontrolled pulmonary, hepatic, renal disease, etc.)
(5) Patients with active hepatitis B.
*HBV DNA should be measured if HBsAg positive, HBsAb positive, and HBc Ab positive.
HBV DNA positivity is excluded.
(6) A man unwilling to contraceptive.
Or pregnant, lactating, pregnant or unwilling women with a positive pregnancy test or unwilling to use contraception.
*However, the following patients may be enrolled.
Women aged 50 years or older and those who have experienced amenorrhea for 12 months or more.
(In cases where exogenous hormone therapy was used, amenorrhea should be present for at least 12 months after discontinuation of all exogenous hormone therapy.)
Among women younger than 50 years, amenorrhea for at least 12 months (more than 12 months after discontinuation of exogenous hormone treatment), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels within the range of postmenopausal at the center reference level, and considered postmenopausal.
Women who have undergone permanent sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (tubal ligation is not possible)
(7)Patients with intractable nausea and vomiting, chronic gastrointestinal disease, dysphagia of the preparation, and total gastrectomy.
(8)Patients of pleural effusion requiring drain drainage, pericardial effusion, and ascites.
*However, patients with stable symptoms after drainage can be enrolled.
(9)Patients contraindicated for necitumumab, carboplatin, nab-paclitaxel, and pembrolizumab.
(10)Patients with synchronous double cancers or metachronous double cancers with disease-free interval of 5 years or less.
*Carcinoma in situ (carcinoma in situ) or intramucosal carcinoma that is judged to be cured by local treatment is not excluded.
(11)Patients in which ingestion is not possible.
(12)Patients in which life expectancy is expected to be 12 weeks or less.
(13)Persons involved in the protocol and conduct of the study (principal investigators, subinvestigators, employees or staff of the participating medical organizations)
(14)Patients who are receiving concomitant medications or herbal supplements with known potent inducing effects on CYP3A4 and are unable to discontinue use at least 3 weeks prior to the first dose of study Drugs used in the Clinical Trial.
(15)Patients with a history of hypersensitivity to necitumumab (or drugs of the same chemical structure or class as necitumumab), carboplatin or nab-paclitaxel or pembrolizumab, or vehicle for these drugs.
(16)Patients with conjunctivitis requiring treatment, hypomagnesemia, and skin disorders.
(17)Patients with hypertension uncontrolled by drug treatment (defined as systolic pressure of 150mmHg or higher or diastolic pressure of 90mg or higher) and patients with active bleeding diathesis
(18)A Patient with Superior Vena Cava Syndrome.
(19)Patients with Grade2 or higher peripheral neuropathy.
(20)Patients with active autoimmune disease that required systemic treatment within the past 2 years.
(21)Patients taking corticosteroids.
(22)Patients with clinically serious heart disease (unstable angina pectoris, onset of myocardial infarction in the 6 months prior to enrollment, etc.), uncontrolled congestive heart failure (NYHA 3,4 degree), or uncontrolled arrhythmias caused by drugs.
(23)Patients with diabetes mellitus requiring insulin therapy.
(24)Other patients who are judged by the investigator or sub-investigator to be inappropriate for participation in the study.

Related Information

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