Study SL-801-0115 is a first-in-human, dose-escalation study in patients with advanced
(i.e., metastatic or locally advanced and unresectable) solid tumors that are resistant to
or relapsed following available standard systemic therapy or for which there is no standard
systemic therapy and additional radiation therapy or other loco-regional therapies are not
considered feasible. Eligible patients will be enrolled and receive treatment with SL-801 in
a 21-day cycle. SL-801 will be administered orally and the dose regimen will depend on the
cohort in which the patient is enrolled.
The study plans to enroll 40-50 adult patients at multiple study centers in the US.
- The patient must have histologic or cytologic evidence of a malignant solid tumor and
must have disease that is resistant to or relapsed following available standard
systemic therapy, or for which there is no standard systemic therapy or reasonable
therapy likely to result in clinical benefit.
- The patient must have advanced disease, defined as cancer that is either metastatic,
OR locally advanced and unresectable (and for which additional radiation therapy or
other locoregional therapies are not considered feasible).
- The patient must have disease that is measurable by standard imaging techniques, per
the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), or
evaluable per RECIST 1.1. (For patients with prior radiation therapy, measurable
lesions must be outside of any prior radiation field[s], unless disease progression
has been documented at that disease site subsequent to radiation.)
- The patient is ≥18 years old.
- The patient has an ECOG PS of 0-2.
- The patient has adequate baseline organ function, as demonstrated by the following:
- Serum creatinine ≤1.5 × institutional upper limit of normal (ULN) or calculated
creatinine clearance >30 mL/min.
- Serum albumin ≥2.5 g/dL.
- Bilirubin ≤1.5 × institutional ULN.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ×
institutional ULN (patients with hepatic metastases must have AST/ALT ≤5 times
- International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN;
and either partial thromboplastin time or activated partial thromboplastin time
(PTT or aPTT) ≤1.5 × ULN.
- The patient has adequate baseline hematologic function, as demonstrated by the
- Absolute neutrophil count (ANC) ≥1.5×10⁹/L
- Hemoglobin ≥8 g/dL, with no red blood cell (RBC) transfusions within the prior
- Platelet count ≥100×10⁹/L, with no platelet transfusions within the prior 14
- If the patient is a woman of child bearing potential (WOCBP), she has had a negative
serum or urine pregnancy test within 1 week prior to treatment.
- The patient (male and female) agrees to use acceptable contraceptive methods for the
duration of time on the study, and continue to use acceptable contraceptive methods
for 1 month after the last dose of SL-801.
- The patient has signed informed consent prior to initiation of any study-specific
procedures or treatment.
- The patient is able to adhere to the study visit schedule and other protocol
requirements, including follow-up for survival assessment.
- The patient has persistent clinically significant ≥Grade 2 toxicities from previous
anticancer therapy (excluding Grade 2 chemotherapy-related neuropathy which is
permitted, and excluding Grade 2-3 laboratory abnormalities if they are not
associated with symptoms, are not considered clinically significant by the
Investigator, and can be managed with available medical therapies).
- The patient has received treatment with chemotherapy, external-beam radiation, or
other systemic anticancer therapy within 14 days prior to C1D1 (28 days for prior
nitrosourea or mitomycin-C). (Patients with advanced prostate cancer who are
receiving luteinizing hormone releasing hormone [LHRH] agonists are permitted onto
the study and should continue use of these agents during study treatment).
- The patient has received treatment with an investigational systemic anticancer agent
within 14 days prior to C1D1.
- The patient has previously received treatment with SL-801 or another investigational
agent that inhibits the XPO1/CRM1 pathway.
- The patient has an additional active malignancy that may confound the assessment of
the study endpoints. Patients with a past cancer history (active malignancy within 2
years prior to study entry) with substantial potential for recurrence must be
discussed with the Sponsor before study entry. Patients with the following
concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in
situ (including transitional cell carcinoma, cervical intraepithelial neoplasia),
organ-confined prostate cancer with no evidence of progressive disease.
- The patient has clinically significant cardiovascular disease (e.g., uncontrolled or
any New York Heart Association Class 3 or 4 congestive heart failure [Appendix 1],
uncontrolled angina, history of myocardial infarction, unstable angina or stroke
within 6 months prior to study entry, uncontrolled hypertension or clinically
significant arrhythmias not controlled by medication).
- The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic
obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's
opinion, would put the patient at significant risk for pulmonary complications during
- The patient has known active or suspected brain or leptomeningeal metastases.
(Central nervous system [CNS] imaging is not required prior to study entry unless
there is a clinical suspicion of CNS involvement). Patients with stable, treated
brain metastases are eligible provided there is no evidence of CNS disease growth on
imaging for at least 3 months following radiation therapy or other locoregional
ablative therapy to the CNS.
- The patient is receiving immunosuppressive therapy for prophylaxis following a prior
organ transplant (solid organ or allogeneic stem cell). Low-dose corticosteroid
therapy is permitted.
- The patient has uncontrolled intercurrent illness including, but not limited to,
uncontrolled infection, disseminated intravascular coagulation, or psychiatric
illness/social situations that would limit compliance with study requirements.
- The patient is pregnant or breast feeding.
- The patient has known positive status for human immunodeficiency virus active or
chronic Hepatitis B or Hepatitis C.
- The patient is oxygen-dependent.
- The patient has any medical condition which in the opinion of the Investigator places
the patient at an unacceptably high risk for toxicities.