Kansas City Research Institute | Kansas City, MO
Status and phase
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About
The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s).
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
HCC part only:
Participants with confirmed diagnosis of unresectable HCC with any of the following criteria:
ST part only (except for HCC):
Participants with histologically or cytologically confirmed diagnosis of solid tumor for which no alternative standard therapy or no effective therapy exists
Life expectancy of >=12 weeks
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1 except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liver function should meet the inclusion criteria)
Adequate washout period before study drug administration:
Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level
At least one measurable lesion based on mRECIST (for HCC Subparts in Dose Escalation Part) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and all subparts in Expansion Part) meeting following criteria
For HCC participants only: Child-Pugh score A. Note: If Child-Pugh score 7 or more was observed during Screening or Baseline, the participant is ineligible and re-assessment of the Child-Pugh score is not permitted
For HCC participants only: Participants categorized to stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment), or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below
a. Participants who have received only one prior line of immuno oncology (IO) based regimen and have progressed on or after prior treatment with IO based regimen, or IO ineligible participants who have received no prior systemic therapy. Participants who previously received lenvatinib treatment are ineligible
For CRC Subpart in Expansion Part only: participants must have received at least 2 prior regimens (not exceeding 4 prior regimens) or could not tolerate standard treatment and must have received the following prior therapies in the metastatic setting if approved and locally available (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 if there is documented disease progression within 6 months of treatment completion Note: If a participant is determined to be intolerant to prior standard treatment, the participant must have received at least of 2 cycles of that therapy Note: Participants who have received oral tyrosine kinase inhibitor (example, regorafenib) are ineligible
For EC Subpart in Expansion Part only: Participants must have EC that has progressed after prior platinum-based chemotherapy and an anti-programmed cell death (ligand) 1 (PD-[L])1)-directed therapy for EC (participants ineligible for IO therapy who have progressed after prior platinum-based chemotherapy are eligible). Up to 3 prior systemic therapies, of which up to 2 for metastatic or locally advanced disease, are permitted Note: There is no restriction regarding prior hormonal therapies
Exclusion criteria
Any of cardiac conditions as follows:
Major surgery within 21 days or minor surgery (that is, simple excision) within 7 days prior to starting study drug. Participant must have recovered from the surgery related toxicities to less than Grade 2 Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
Known to be human immunodeficiency virus (HIV) positive Note: the sponsor has evaluated whether to include participant with HIV. Given that this is the first combination study of E7386 with lenvatinib and that the main mechanism of action of E7386 is immunomodulation of the tumor microenvironment along with the fact that several anti-retroviral therapies have drug-drug interaction with cytochrome P450 3A (CYP3A) substrates, the sponsor has decided not to include these participants at the current time. However, further considerations will be made moving forward based on new emerging data Note: HIV testing is required at screening only when mandated by local health authority
Participants with proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein >=1 gram per 24 hour will be ineligible
Active infection requiring systemic treatment (Except for Hepatitis B and/or C [HBV/HCV] infection in HCC participants)
In case of HBsAg (+) participants in HCC participants:
Diagnosed with meningeal carcinomatosis
Participants with central nervous system metastases are only eligible if they have been previously treated and are radiologically stable, (that is, without evidence of progression for at least 4 weeks prior to first dose of study treatment by repeat imaging), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
Any of bone disease/conditions as follows:
History of malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ [example, bladder or cervix]) within the past 24 months prior to the first dose of study drug
For HCC Subpart in Dose Escalation Part only: Participants who experienced discontinuation of lenvatinib, 2 or more dose reductions of lenvatinib required from initial dose level of this study due to its toxicity, or participants who experienced single dose reduction or consecutive >=8 days dose interruption of lenvatinib within 60 days from the first dose, due to its toxicity. EC Subpart in Expansion Part only: Participants previously treated with lenvatinib who experienced discontinuation of lenvatinib due to toxicity, or dose reduction to less than 10 mg of lenvatinib due to toxicity within 60 days from the first dose
Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic International Normalized Ratio (INR) monitoring for HCC participants only (example, warfarin or similar agents). Treatment with low molecular weight heparin and factor X inhibitors is permitted. Treatment with antiplatelet agents is prohibited for HCC participants in Dose Escalation Part only
Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
For HCC participants only: History of hepatic encephalopathy within 6 months prior to starting study drug
For EC Subpart in Expansion Part only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial stromal sarcomas
Has preexisting >=Grade 3 gastrointestinal or non-gastrointestinal fistula
Evidence of current Coronavirus disease 2019 (COVID-19) infection or ongoing unrecovered active sequelae of COVID-19 infection
Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and after study drug discontinuation). No sperm donation is allowed during the study period and after study drug discontinuation
Has a known psychiatric or substance abuse disorder that would interfere with the participant ability to cooperate with the requirements of the study
Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the participant safety or interfere with the study assessments
Scheduled for major surgery during the study
Primary purpose
Allocation
Interventional model
Masking
181 participants in 8 patient groups
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Eisai Inquiry Service
Data sourced from clinicaltrials.gov
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