2023-510275-64-00
Recruiting
Phase 1/2
An Open-Label Study of E7386 in Combination With Other Anticancer Drug(s) in Subjects With Solid Tumors
Overview
- Phase
- Phase 1/2
- Status
- Recruiting
- Sponsor
- Eisai Limited
- Enrollment
- 83
- Locations
- 28
- Primary Endpoint
- Safety related endpoints including DLT and/or defining the RP2D ORR defined as the proportion of subjects who have BOR of confirmed CR or PR per RECIST 1.1 by investigator assessment (Dose Optimization Parts only)
Overview
Brief Summary
• To assess safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s). • EC Dose Optimization Part only: To determine the optimal dose of E7386 in combination with lenvatinib in EC.
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •For HCC subjects only Subjects with confirmed diagnosis of unresectable HCC with any of the following criteria: a. Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors b. Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection (see Appendix 11) For other ST subjects (ie, except for HCC subjects) Subjects with histologically or cytologically confirmed diagnosis of solid tumor for which no alternative standard therapy or no effective therapy exists
- •Adequate liver function
- •Adequate serum mineral level
- •see protocol
- •At least one measurable lesion based on modified RECIST (mRECIST; for HCC Subparts in Dose Escalation Part [see Appendix 5]) or on RECIST 1.1 (see Appendix 4) for Other ST Subparts in Dose Escalation Part and all subparts in Expansion and Dose Optimization Parts) meeting following criteria: – At least 1 lesion of ≥1.0 cm in the longest diameter for a non-lymph node or ≥1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1 using computerized tomography (CT)/magnetic resonance imaging (MRI) – Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation, or transarterial chemoembolization (TACE)/transarterial embolization (TAE) must show evidence of disease progression based on RECIST 1.1 to be deemed a target lesion
- •For HCC subjects only: Child-Pugh score A. Note: If Child-Pugh score 7 or more was observed during Screening or Baseline, the subject is ineligible and re-assessment of the Child-Pugh score is not permitted.
- •For HCC subjects only: Subjects 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.
- •see protocol
- •For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below a. Subjects who have received only 1 prior line of IO-based regimen and have progressed on or after prior treatment with IO-based regimen, or IO ineligible subjects who have received no prior systemic therapy. Subjects who previously received lenvatinib treatment are ineligible
- •For CRC Subpart in Expansion Part only: subjects 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 subject is determined to be intolerant to prior standard treatment, the subject must have received at least of 2 cycles of that therapy. Note: Subjects who have received oral tyrosine kinase inhibitor (eg, regorafenib) are ineligible. a. Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-VEGF monoclonal antibody (mAb) (eg, bevacizumab) Note: Capecitabine is acceptable as equivalent to fluoropyrimidine in prior treatment. Note: Subjects who have previously received fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only chemotherapy regimen, eg, FOLFOXIRI or FOLFIRINOX, may be eligible after discussion with the Sponsor. b. Chemotherapy with anti-EGFR mAb (cetuximab or panitumumab) for subjects with RAS (KRAS/NRAS) wild type (WT) CRC Note: RAS (KRAS/NRAS) WT subjects with right or left CRC lesions who may have not been treated with anti-EGFR mAb based on local guidelines are eligible. c. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors d. Immune checkpoint inhibitor for subjects with microsatellite instability-high (MSI-H) CRC
Exclusion Criteria
- •Any of cardiac conditions as follows: - Heart failure New York Heart Association (NYHA) Class II or above - Prolongation of corrected QT (QTcF) interval to >480 ms - Left ventricular ejection fraction (LVEF) <50%
- •see protocol
- •see protocol
- •Any of bone disease/conditions as follows: – T-score of <–3.0 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by dual energy x-ray absorptiometry (DXA) scan. Subjects with T-score <-2.5 to -3.0 can only be included if treatment with a bisphosphonate (eg, zoledronic acid) or denosumab has been started at least 14 days and no more than 6 months prior to the first dose of study drug – Metabolic bone disease, such as hyperparathyroidism, Paget’s disease, or osteomalacia – Symptomatic hypercalcemia requiring bisphosphonate therapy – History of any fracture within 6 months prior to starting study drug – Bone metastasis requiring orthopedic intervention – Bone metastasis not being treated by bisphosphonate or denosumab. Subject may be included if treatment with bisphosphonate or denosumab have been started at least 14 days prior to the first dose of study drug. Subjects with previous solitary bone lesions controlled with radiotherapy are eligible – History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less) – Moderate (25% to 40% decrease in the height of any vertebrae) or severe (>40% decrease in the height of any vertebrae) morphometric vertebral fracture at Baseline
- •see protocol
- •see protocol
- •History of malignancy (except for original disease, or definitively treated melanoma in situ, basal or squamous cell carcinoma of the skin, carcinoma in situ [eg, bladder or cervix]) within the past 24 months prior to the first dose of study drug
- •see protocol
- •see protocol
- •For HCC Subpart in Dose Escalation Part only: Subjects 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 subjects who experienced single dose reduction or consecutive ≥8 days dose interruption of lenvatinib within 60 days from the first dose, due to its toxicity. HCC Subpart in Expansion Part only: Subjects who previously received lenvatinib treatment are ineligible. EC Subpart in Expansion Part only: Subjects 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 . EC Dose Optimization Part only: Subjects who previously received lenvatinib treatment are ineligible.
Outcomes
Primary Outcomes
Safety related endpoints including DLT and/or defining the RP2D ORR defined as the proportion of subjects who have BOR of confirmed CR or PR per RECIST 1.1 by investigator assessment (Dose Optimization Parts only)
Safety related endpoints including DLT and/or defining the RP2D ORR defined as the proportion of subjects who have BOR of confirmed CR or PR per RECIST 1.1 by investigator assessment (Dose Optimization Parts only)
Secondary Outcomes
- PK profile of study drug(s)
- BOR
- ORR (Dose Escalation and Dose Expansion Parts)
- DCR: defined as the proportion of subjects who have a BOR of CR or PR, or SD
- CBR: defined as the proportion of subjects who have a BOR of CR or PR, or durable SD
- PFS: defined as the time from the first dose of study drug to the first documentation of PD or death due to any cause (whichever occurs first)
- DOR: among subjects with PR or CR, defined as the time from the first documentation of PR or CR to the first documentation of PD or death due to any cause (whichever occurs first)
- OS (all subparts in Expansion and Dose Optimization Part and HCC Subparts in Dose Escalation Part): defined as the time from the first dose of study drug to death due to any cause
Investigators
Medical Information
Scientific
Eisai Limited
Study Sites (28)
Loading locations...
Similar Trials
Not yet recruiting
Phase 2
A Phase 2a Study of the Safety and Efficacy of OD-07656 and of Subsequent Vedolizumab Therapy in Moderately to Severely Active Ulcerative Colitis2024-520201-39-00Odyssey Therapeutics Inc.47
Recruiting
Phase 2
A Trial of SHR-7787 Injection Combined With Other Anti-tumor Drugs in Patients With Malignant Solid TumorsNCT07268040Shanghai Hengrui Pharmaceutical Co., Ltd.400
Active, not recruiting
Phase 1/2
A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (THOR-707-101)2023-508422-95-00Synthorx Inc.31
Recruiting
Phase 2
A study to evaluate KER-050 as a monotherapy or in combination with Ruxolitinib in Myelofibrosis.2023-507468-38-00Keros Therapeutics Inc.56
Active, not recruiting
Phase 1/2
A clinical trial to evaluate the safety and effectiveness of a combination of either AG-12or AG-221 tablets with azacitidine injections in patients withnewly diagnosed Acute Myeloid Leukemia (AML) and who have mutations in enzymes isocitrate dehydrogenase 1 or 2 (IDH 1 or IDH2) and are not candidates to receive intensive induction chemotherapy.2024-511722-31-00Celgene Corp.70