A Phase 1b/2 Study of E7386 when combined with Pembrolizumab in cancer patients previously treated
- Conditions
- Melanoma, colorectal carcinoma, hepatocellular carcinomaMedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-001568-10-ES
- Lead Sponsor
- Eisai Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 108
- Male or female, age =18 years (or any age greater than 18 years as determined by country legislation) at the time of informed consent.
- Life expectancy of =12 weeks
- Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) selected solid tumour for which prior standard systemic therapy has failed. Selected tumor types: melanoma (excluding uveal melanoma), CRC, HCC regardless of line of therapy received.
Phase 2 (melanoma only)- subject must have:
a. Unresectable Stage III or Stage IV melanoma, per American Joint Committee on Cancer staging system version 8, not amenable to local therapy.
b. At least one measurable lesion by computer topography (CT) or magnetic resonance imagery (MRI) based on RECIST 1.1 (cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol but may be considered as nontarget lesions). Lesions in a previously irradiated area should not be considered measurable unless there has been documented growth of the lesions since the completion of radiotherapy (please see Amendment 02 for remaining details)
For CRC Cohort only (Phase 2 part), subjects must have received at least two prior systemic therapies from the following, in adjuvant and/or metastatic setting, if approved and locally available (not exceeding 4 lines of therapies in the metastatic setting, progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment):
Note: Adjuvant chemotherapy counts as prior systemic treatment in the metastatic setting if there is documented disease progression within 6 months of treatment completion.
Note: If a subject is determined to be intolerant to prior standard treatment, the subject must have received at least of 2 cycles of that therapy.
PLEASE SEE PROTOCOL FOR FULL DETAILS AND LIST OF INCLUSION CRITERIA
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 54
Subjects who meet any of the following criteria will be excluded from this study:
1. History of other active malignancy (except for original disease, or definitively treated basal or squamous cell skin carcinoma, carcinoma in-situ of the bladder or cervix) within the past 24 months prior to the first dose of study drug.
2. Major surgery within 21 days prior to starting study drug or minor surgery within 1 week (subject must also have recovered from any surgery-related toxicities to less than CTCAE Grade 2).
3. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition that might impair the bioavailability of E7386 in the opinion of the investigator(s).
4. Any of the cardiac conditions as follows:
- New York Heart Association (NYHA) congestive heart failure Class II or above
- Unstable ischemic heart disease (myocardial infarction within 6 months prior to starting study drug, or angina, other than adequately controlled mild exertional angina.
- Serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months
- Prolongation of corrected QT (QTcF) interval to >450 msec
- Left ventricular ejection fraction (LVEF) <50%
5. Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to study drug administration. The subject can receive diuretic drugs as needed per the treating physician, outside of the above-mentioned conditions. Consult with the sponsor if the subject has more than trivial/trace fluid accumulation.
6. Prior treatment with E7386, or has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, [CTLA-4], OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related (ir)AE.
7. Subjects who have received treatments below before first study drug administration:
a. Any prior anticancer treatment: within 4 weeks or 5 times the half-life, whichever is shorter
b. Any investigational drug or device: within 4 weeks
c. For study drugs in other studies such as mAbs with half-lives >10 days: within 56 days
d. Radiotherapy: within 2 weeks of start of study drug. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
e. Have received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
f. Has not recovered adequately from the toxicity and/or complications from the intervention if subject received major surgery prior to starting study drug.
g. Drugs or supplements that are known potent cytochrome P450 3A (CYP3A) inducers/inhibitors or substrates with narrow therapeutic indices within 4 weeks before study drug administration.
PLEASE SEE PROTOCOL FOR FULL DETAILS AND LIST OF EXCLUSION CRITERIA
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method