All Cohorts
Prior anti-PD-1 treatment for combination dose expansion cohorts 3a - 3d
Prior anti-PD-1 treatment for combination dose expansion cohorts 3e - 3h
For deep tumor cohorts, patients who require uninterrupted anticoagulants of any type, on daily aspirin therapy, or NSAIAs.
Patients in expansion cohorts A and B must have measurable disease
EXPANSION COHORTS ONLY
For cohorts B1 and B2 only, biopsy confirmation of metastases (if safe and feasible at treating center)
DISEASE SPECIFIC EXPANSION COHORTS: Prior receipt of docetaxel is not permitted
For the expansion cohorts only: prior treatment with any MEK inhibitor is not allowed in the expansion cohorts
Have measurable disease based on:\r\n* Lugano classification (cohorts A, C)\r\n* International Workshop on CLL (cohorts B, D)
(For both cohorts A and B): Platelets >= 100 x 10^9/L
(For both cohorts A and B): Serum albumin > 2
Prior yttrium-90 therapy for patients in cohorts 1 or 2
For hypomethylating failure cohorts only, more than 4 months since last cycle of HMA
For which there are no standard therapies available (Cohorts 1, 3, 4 and 5)
For the combination cohorts (cohorts 5 and 6 in Part 1) and Part 2, subjects with metastatic melanoma or NSCLC do not need to have received prior therapy
Subjects must not be candidates for hepatic surgery or locoregional therapy of liver tumors with curative intent or planned systemic anti-cancer therapy, with the exception of immunotherapy in the combination cohorts (Cohorts 5 and 6 in Part 1 and all subjects in Part 2).
Previous treatment with lenvatinib (except for participants previously enrolled into Cohorts 1 or 2B of this study).
Smokers and subjects who use smokeless tobacco products are excluded in all cohorts
Phase II cohorts only: patients must have measurable disease according to RECIST v.1.1 criteria. Patients enrolled in Ph Ib cohorts must have evaluable disease
Meets criteria for 1 of the 4 defined study cohorts
ADDITIONAL CRITERIA FOR COHORTS 1A AND 1B PARTICIPANTS ONLY: No corticosteroid dosing within 5 days of study therapy initiation
For patients enrolling in the four expansion cohorts:
For all cohorts:
For all cohorts:
For both cohorts:
For both cohorts:
Agreement to the collection of serial fresh lesion samples (required, if feasible, for entry into Escalation Cohorts 4 and Expansion Cohorts A & B and optional, but encouraged in Escalation Cohorts 2 & 3 and Expansion Cohort C)
ALL COHORTS
Dose Expansion: Solid Tumors Not Otherwise Eligible for the Cholangiocarcinoma, Chondrosarcoma, or Non-enhancing Glioma Cohorts
Previous treatment with radiotherapy and temozolomide (Cohorts 1, 1b and 2 only)
Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer:
At least one site of accessible disease for pre- and post-treatment core biopsies for at least 20 patients per arm on the expansion cohorts.
Participants for Cohorts B and C:
Participants for Cohorts D and E:
Participants for Cohorts A, C, and E:
Potential Participants for Cohorts A, C or E who are to Receive Binimetinib:
Potential Participants for Cohorts A, C, D or E:
Potential Participants for Cohorts D or E:
Albumin >= 2.5 g/dL\r\n* NOTE: this applies to patient in the normal and renal dysfunction cohorts (N, R3 and R4); abnormal albumin is allowed for patients in the liver dysfunction cohorts
FURTHER ELIGIBILITY DETAILS FOR PATIENTS WITH PROGRESSIVE DISEASE (COHORTS 1 AND 3A/3B):
Any prior treatment with capecitabine for patients enrolled to cohorts 3a/3b and prior lapatinib for participants on cohort 3a
Safety and Expansion Cohorts
Part 2 (Expansion) only: Subject must be able to be stratified into 1 of 3 cohorts:
MESOTHELIOMA COHORTS (COHORTS 1 AND 2 ONLY): Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
Total bilirubin: see guidelines for individual cohorts
B) Dose Expansion Cohorts:
for intratumoral cohorts, injection of tumor would require violation of ventricular system
For participants in all combination arms (Cohorts A-E), use or consumption of any of the following substances:
Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance status of: 0 - 1 (dose escalation cohorts) or 0 - 2 (expansion cohorts)
Cohorts A & B:
Patients will be enrolled in one of the two cohorts based on diagnosis:
NSCLC patients of all histologies may enroll to cohorts 1 and 2; only patients of non-squamous histologies may enroll to cohort 3; if enrollment to a cohort is completed, enrollment may continue to other open cohorts
Dose and Disease Expansion Cohorts
Part 2: Subjects will be enrolled into 1 of 3 cohorts:
Note, the line of therapy limit does not apply to the biopsy substudy cohorts.
For participants enrolled in the expansion cohorts in which tumor biopsies are obtained: