Status and phase
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About
SLC-391 is a novel, potent and specific small molecule inhibitor of receptor tyrosine kinase AXL with desirable potency and pharmaceutical properties.
The study is being done to evaluate the safety and pharmacokinetic (PK) profile of SLC-391 in combination with pembrolizumab in participants with non-small cell lung cancer (NSCLC).
Each treatment cycle lasts 21 days. Participants will swallow SLC-391 pills two times every day. Participants will get pembrolizumab intravenously (IV) from the study site staff on the first day of every cycle.
This study has 2 parts. The first part will determine the recommended dose of SLC-391 in combination with pembrolizumab. The second part wants to find out if the combination of SLC-391 and pembrolizumab can help stop NSCLC tumours from growing or spreading.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
The subject provides written informed consent.
Adults ≥ 18 years of age on day of signing informed consent.
Disease must be measurable per RECIST 1.1, as assessed by the Site(s) Investigator/radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in these lesions.
Subject has histologically or cytologically documented, locally advanced (Stage IIIB or IIIC) disease (not candidate for surgical resection, local therapies with curative intent, or definitive chemoradiation) or the subject has metastatic NSCLC (Stage IV). Staging will be based on the American Joint Committee on Cancer, Eighth Edition. Subjects with adenocarcinoma, large cell carcinoma, undifferentiated carcinoma, squamous carcinoma, or mixed histology are eligible. Subjects with a small cell component are not eligible.
Phase 1b Subjects additional eligibility criteria:
Phase 1b Notes:
Cohort 1:
Cohort 2:
Cohort 2 Notes:
Targeted therapy for advanced setting is counted as a prior line of therapy.
Maintenance therapy is not counted as a prior line of therapy.
Neoadjuvant and adjuvant therapies initiated < 12 months prior to first dose of study drug(s) will be counted as one prior line of therapy for advanced setting.
Neoadjuvant and adjuvant therapies initiated ≥ 12 months prior to first dose of study drug(s) are not counted as prior lines of therapy.
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Life expectancy of at least 3 months.
An archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated must exist to participate in the study (Mandatory in Phase 2a but subjects in Phase 1b may be enrolled in the absence of a tumor tissue sample). Only core needle and/or excisional biopsy samples, from archival or fresh tissue, will be accepted in this study.
Adequate organ function as defined below must be met for subjects to participate in the study. Clinical laboratory specimens must be collected within 10 days prior to first dose of study drug(s):
Absolute neutrophil count (ANC) ≥ 1500/µL or ≥ 1.5 × 109/L (in the absence of growth factor support).
Platelets ≥ 100,000/µL or 100 × 109/L (in the absence of transfusion or growth factor support).
Hemoglobin ≥ 9 g/dL or ≥ 90 g/L (in the absence of transfusion). Note: Criteria must be met without packed red blood cell transfusion within the prior 2 weeks. Subjects can be on stable dose of erythropoietin (≥ approximately 3 months).
Creatinine Clearance (CCr) ≥ 50 mL/minute using the Cockcroft and Gault formula.
Note: The Cockcroft and Gault formula (1973): CCr = ([{140 - age} × weight]/[72 × SCr]) × 0.85 (if female); where CCr = mL/minute; age = years; weight = kg; SCr (serum creatinine) = mg/dL.
Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (unless a diagnosis of Gilbert's syndrome in which case ≤ 3 × ULN) OR direct bilirubin ≤ 1 × ULN for participants with total bilirubin >1.5 × ULN.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5× ULN for subjects with liver metastases).
International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; if the subject is receiving anticoagulant therapy PT or INR should be within the therapeutic range of the intended use of anticoagulants.
Activated partial thromboplastin time/partial thromboplastin time (aPTT/PTT) ≤ 1.5 × ULN; if the subject is receiving anticoagulant therapy PTT should be within the therapeutic range of intended use of anticoagulants.
Note: Low molecular weight heparin, warfarin (INR monitoring required), direct oral anticoagulants, and drugs in the anticoagulant class (e.g., Lovenox [enoxaparin]) administered for deep vein thrombosis are permitted.
Women who are not of childbearing potential must be documented and will not be tested for pregnancy or required to utilize contraception if they meet one or more of the following definitions of non-childbearing potential:
Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum) within 72 hours prior to first dose of study drug(s) and meet the following criteria throughout the study, starting with the screening visit through 120 days after the last dose of study drug(s) (or 30 days if new cancer therapy is initiated):
Agrees to follow contraceptive guidance throughout the study as per protocol.
Willing to use 2 highly effective birth control methods throughout the study. The 2 birth control methods can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Refer to Appendix 4 for complete list of acceptable birth control methods.
Refrain from egg donation. Note: If there is any question that a subject will not reliably comply with the requirements for contraception, that subject should not be enrolled.
Male subjects must agree to use an acceptable method of contraception and refrain from sperm donation throughout the study: from screening, during the treatment period, and for at least 120 days after the last dose of study drug(s) (or 30 days if new cancer therapy is initiated).
Willing and able to participate in blood sampling and all other required study procedures.
Exclusion criteria
Phase 2a - Cohort 1 (only) exclusion criteria:
Undergone prior treatment with a known AXL inhibitor such as bemcentinib (see Section 8.2.2 for full list of AXL inhibitors).
Received prior systemic anticancer therapy within 5 half-lives or 3 weeks, whichever is shorter, prior to starting the first dose of study drug(s). Examples of prior systemic anticancer therapy includes cytotoxic agents, targeted therapy such as small molecules, mAbs and hormonal therapy etc..
Received immunotherapies [including but not limited to PD(L)-1 inhibitors, etc.] within 4 weeks prior to starting the first dose of study drug(s).
Received prior radiotherapy within 2 weeks of the first dose of study drug(s) or had a history of radiation pneumonitis.
Note: Subjects must have recovered from all radiation-related toxicities and not require corticosteroids. A 1 week washout is permitted following palliative radiation (≤ 2 weeks of radiotherapy) for non-central nervous system (CNS) disease.
Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent, follow-up is primarily non-invasive, and the subject can comply with protocol requirements.
Note: Subject with ≤ Grade 2 neuropathy may be an exception to this criterion and may qualify for the study after discussion with Sponsor. Subjects with endocrine-related AEs ≤ Grade 2 requiring treatment or hormone replacement may be eligible after discussion with Sponsor.
Note: Toxic effects also include laboratory results that have not resolved to ≤ Grade 1. Subjects with ≤ Grade 2 alopecia are an exception to this criterion.
Note: The administration of killed vaccines, mRNA vaccines, and DNA vaccines is allowed.
Note: Hormone therapy (e.g., thyroxine, insulin, or corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
Note: Subjects with curatively treated basal or squamous cell carcinoma of the skin (non-melanoma skin cancer), cervical or vaginal intra-epithelial neoplasia, non-invasive breast cancer in situ, or localized prostate cancer with a prostate-specific antigen level of < 4 ng/mL (µg/L) at screening are not excluded. Subjects with other curatively treated malignancies who have had a > 2-year disease-free interval and whose natural history or treatment does not have the potential to interfere with investigational agents (e.g., hormone maintenance) may be enrolled after approval by the Medical Monitor/Sponsor.
Known active CNS metastases and/or carcinomatous meningitis. Subjects with adequately treated brain metastases may participate provided they meet the following criteria:
Severe hypersensitivity (≥ Grade 3) to pembrolizumab or SLC-391 and/or any excipients.
A history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
A known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies). No HIV testing is required unless mandated by the local health authority.
Known history of Hepatitis B (Anti-HBc and HBsAg reactive) or known active Hepatitis C virus (RNA, qualitative) infection.
Note: No testing for Hepatitis B or C is required unless mandated by a local health authority.
Note: TB testing is required for subjects recently exposed to persons with active TB or who have traveled recently to areas where TB is endemic.
Note: If a subject has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker as deemed by the Investigator (i.e., the subject otherwise has no cardiac abnormalities), the subject may be eligible to participate in the study following discussion with the Sponsor.
Note: The Investigator or licensed, medically qualified Sub-Investigator must review and confirm eligibility prior to the first dose of study drug(s).
Primary purpose
Allocation
Interventional model
Masking
92 participants in 5 patient groups
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Central trial contact
Zaihui Zhang, PhD; Madhu Singh, PhD
Data sourced from clinicaltrials.gov
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