Phase II Trial of Ubenimex Combined with Pembrolizumab + nab-Paclitaxel + Carboplatin for Untreated Patients with Advanced Squamous Non-Small Cell Lung Cancer: (UBE-Q)

JRCT ID: jRCT2031210707

Registered date:30/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: squamous non-small cell lung cancer(SqCLC)
• Date of first enrollment: 04/01/2023
• Target sample size: 54
• Study type: Interventional

Intervention(s)

<Confirmation of Tolerability Part>
Tolerability of pembrolizumab plus nab-paclitaxel plus carboplatin in combination with ubenimex will be confirmed in the validation part and dose-levels will be determined in the efficacy assessment part.
The dose of ubenimex will begin at level 1 (30 mg/body/day) and increase to level 2 (60 mg/body/day) and level 3 (120 mg/body/day) according to the escalation criteria.
<Efficacy Evaluation Part>
To investigate the efficacy and safety of combining umbenimex with pembrolizumab plus nab-paclitaxel plus carboplatin therapy at dose-levels determined in the validation part of tolerability.

Outcome(s)

• Primary Outcome: Response Rate by Central Response Evaluation(FAS)

Secondary Outcome

(1)1-year PFS(FAS,PPS)
(2)OS(FAS,PPS)
(3)PFS(FAS,PPS)
(4)Investigator-adjudicated ORR(FAS),Central response assessment and investigator-adjudicated ORR(PPS)
(5)DCR(FAS,PPS)
(6)Safety (incidence and severity of adverse events,SAF)

Key inclusion & exclusion criteria

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

Include criteria

1) Patients with histologically or cytologically diagnosed lung squamous cell carcinoma.
* Non-small cell carcinoma containing components of squamous cell carcinoma is eligible.
2) Patients with clinical stage 3B, 3C or 4 or postoperative recurrence who are not candidates for definitive radiotherapy.
3) Patients who have not received systemic chemotherapy (including targeted agents and immune checkpoint inhibitors) or definitive thoracic radiotherapy, including treatment for other cancer types.
* Neoadjuvant chemotherapy without molecular targeted agents or immune checkpoint inhibitors can be registered if more than 6 months have passed since the date of last treatment.Previous postoperative UFT treatment will be eligible regardless of the number of days elapsed since the last dose.
* Surgery or hormone therapy for other cancer types is eligible.
4) Individuals with measurable disease based on RECIST(version1.1) in imaging studies performed within 28 days prior to enrollment.
5)Patients who meet the following criteria for major organ function within 14 days before enrollment
Neutrophil count 1500 per mm3 or higher
Platelet count 100,000 per mm3 or higher
Haemoglobin 9.0 g/dL or more
Total bilirubin 2.0 mg/dL or less
AST,ALT 100 U/L or less (200 U/L for hepatic involvement).
Serum creatinine clearance *Calculated by 45 mL/min (Cockcroft-Gault involvement)
* Estimates by Cockcroft-Gault equation or 24--h urine collection method.
Body surface area correction is not performed with the 24-hour urine collection method.
* Eligible if the estimated value is less than 45 mL/min and the measured value by the 24-hour urine collection method is 45 mL/min or more.
* Cockcroft-Gault formula male:CCr = {(140-age)*body weight (kg)}/{72* serum creatinine level (mg/dL)} female: CCr = 0.85* {(140-age)*body weight (kg)}/{72*serum creatinine level (mg/dL)}
SpO2 (under room air) 92% or more
6) Individuals with a ECOG Performance Status (PS) of 0 or 1
7) Patients aged 20 years or older at the time of informed consent
8) Patients who are likely to survive more than 3 months
9) Orally available patients
10) Patients for whom written informed consent has been obtained from the patient for participation in the study before enrollment.

Exclude criteria

1) Patients with interstitial lung disease (ILD), drug-induced ILD, previous radiation pneumonitis requiring steroid treatment, or active ILD.
2) Patients with active double cancers.
* Double cancers are synchronous double cancers and metachronous double cancers with disease-free intervals of less than 2 years, and Carcinoma in situ (carcinoma in situ) or intramucosal carcinoma-equivalent lesions that are judged to be cured by local treatment should not be included in active duplicate cancers.
3) Patients with infections requiring systemic treatment.
4) Patients receiving palliative radiotherapy for lung cancer metastases within 14 days before enrollment (eligible if palliative radiotherapy was completed before 15 days before enrollment)
5)Patients with symptomatic brain metastases, meningeal carcinomatosis, and spinal metastases requiring radiotherapy or surgery.
6) Those requiring more than Grade 3 pleural, pericardial, and ascitic fluid collections requiring drainage (pleural fluid collections must be excluded unless Grade 3 or more pleural fluid collections occur 14 days after drainage followed by pleurodesis)
7) Patients with a history of drug-induced hypersensitivity requiring systemic treatment, such as anaphylaxis, and patients with hypersensitivity to components of pembrolizumab, carboplatin, or nab-paclitaxel.
8) Patients with active autoimmune disease requiring systemic treatment within the past 2 years.
9) Patients who are chronically taking systemic steroids (10mg or more in predonine equivalents)
10) Patients with active hepatitis B (HBsAg-positive patients)
11) Individuals with concomitant HIV infection (HIV-1/HIV-2 antibody-positive)
(The exclusion criteria are not met if HIV antibody-test history is confirmed and a negative result can be confirmed.)
12) Patients with medically important and uncontrollable complications.
13)Patients who fall under the following conditions (acceptable contraceptive methods are listed separately below*)
Men unable to perform adequate contraception during the study period and at least 90 days after completion of the study.
Women of childbearing potential who are unable to perform adequate contraception during the study period and at least 90 days after the end of the study (women who have not passed one year after menopause, women who are not in permanent infertility due to surgery (ovarian, fallopian tube and/or hysterectomy) or other causes (such as Mullerian agenesis) are considered fertile)
Pregnant or breastfeeding women (breastfeeding women are defined as meeting exclusion criteria even if breastfeeding is interrupted)
Women with a positive pregnancy test result performed before the start of study Drugs used in the Clinical Trial.
14) Other patients who are deemed inappropriate for participation in the study by the principal investigator or sub-investigator.
*[About acceptable contraceptive methods].
Effective contraceptive methods always combine multiple contraceptive methods, including contraceptive methods with an annual failure rate of less than 1%, even when used consistently and correctly, as described in ICH guidance.
1)Acceptable contraceptive method
Condom
Contraceptive methods with an annual failure rate of less than 1% (tubal ligation, male sterilization, established and appropriate use of contraceptives (hormonal agents) to inhibit ovulation, hormonally added intrauterine contraceptive systems, copper-added intrauterine devices)
Complete abstinence
2)Unacceptable contraceptive method
Cyclic abstinence (calendar method, ovulation method, symptomatic temperature method, postovulation method, etc.)
Extravaginal ejaculation

Related Information

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