Trial Title:
Testing Experimental Anti-cancer Drug SLC-391 With an Approved Immunotherapy Drug, Pembrolizumab, for Advanced Lung Cancers
NCT ID:
NCT05860296
Condition:
Lung Cancer, Nonsmall Cell
Lung Cancer Stage IV
Lung Cancer Metastatic
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
SLC-391
Description:
SLC-391 is an AXL inhibitor
Arm group label:
Dose Escalation (Phase 1b Dose Level -1)
Arm group label:
Dose Escalation (Phase 1b Dose Level 1)
Arm group label:
Dose Escalation (Phase 1b Dose Level 2)
Arm group label:
ICI-Naïve (Phase 2a)
Arm group label:
ICI-Resistant (Phase 2a)
Intervention type:
Biological
Intervention name:
pembrolizumab
Description:
Immunotherapy
Arm group label:
Dose Escalation (Phase 1b Dose Level -1)
Arm group label:
Dose Escalation (Phase 1b Dose Level 1)
Arm group label:
Dose Escalation (Phase 1b Dose Level 2)
Arm group label:
ICI-Naïve (Phase 2a)
Arm group label:
ICI-Resistant (Phase 2a)
Other name:
KEYTRUDA®
Summary:
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.
Criteria for eligibility:
Criteria:
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:
1. Subjects must have received a minimum of one prior systemic treatment for
advanced unresectable or metastatic NSCLC and progressed following prior SOC.
2. Maximum of up to 4 prior lines of therapy in an advanced or metastatic setting
is allowed.
3. Subjects who had disease recurrence or progression following neoadjuvant or
adjuvant therapy or definitive chemoradiation therapy are eligible.
4. Subjects who received treatment with an approved/available targeted therapy for
an actionable genomic alteration (including but not limited to EGFR, ALK, ROS1,
KRAS, etc.) can participate if they have documented disease progression or were
unable to tolerate the approved targeted therapy.
Phase 1b Notes:
- Targeted therapy for advanced setting is counted as a prior line of therapy.
- Prior use of a PD(L)-1, anti-CTLA-4 (Cytotoxic T-lymphocyte associated protein 4)
antibody, or any other antibody or drug that specifically targets immune checkpoint
pathway is allowed and is counted as a prior line of therapy.
- Neoadjuvant and adjuvant therapies initiated < 12 months prior to the 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 the first dose of
study drug(s) are not counted as prior lines of therapy.
- Maintenance therapy is not counted as a prior line of therapy.
- Phase 2a Subjects additional eligibility criteria:
Cohort 1:
1. Tumors must have PD-L1 expression (TPS ≥ 1% as determined by SOC).
2. Subjects are eligible to participate if they did not receive any prior therapy (SOC
or investigational) or prior immunotherapy of any kind for advanced or metastatic
disease. See Exclusion Criteria 1.0.
3. Subjects with disease recurrence or progression following neoadjuvant or adjuvant
therapy or definitive chemoradiation therapy are eligible.
4. Prior adjuvant or neoadjuvant immunotherapy is allowed if completed more than 12
months before documented relapse.
Cohort 2:
1. Subjects should have received at least 2 doses of an approved anti PD(L) 1
monoclonal antibody (mAb) in an advanced or metastatic setting.
2. Progressive disease should be documented during treatment or within 12 weeks from
the last dose of anti-PD(L)-1 mAb.
3. Up to a maximum of 2 prior lines of approved cancer therapy in an advanced or
metastatic setting, including an anti-PD(L)-1 mAb administered either as monotherapy
or in combination with other therapies, is allowed.
4. Subjects who received treatment with an approved/available targeted therapy for an
actionable genomic alteration (including but not limited to EGFR, ALK, ROS1, KRAS,
etc.) can participate if they have documented disease progression or were unable to
tolerate the approved targeted therapy. Only these subjects are allowed to receive
up to a maximum of 3 prior lines of cancer therapy in an advanced or metastatic
setting.
5. Subjects with disease recurrence or progression following neoadjuvant or adjuvant
therapy or definitive chemoradiation therapy are eligible.
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):
1. Absolute neutrophil count (ANC) ≥ 1500/µL or ≥ 1.5 × 109/L (in the absence of
growth factor support).
2. Platelets ≥ 100,000/µL or 100 × 109/L (in the absence of transfusion or growth
factor support).
3. 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).
4. 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.
5. 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.
6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
(≤ 5× ULN for subjects with liver metastases).
7. 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.
8. 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:
1. Amenorrheic for > 2 years without a hysterectomy and oophorectomy, and a
follicle stimulating hormone (FSH) value in the postmenopausal range upon
screening evaluation.
2. Post-hysterectomy, bilateral oophorectomy, or tubal ligation. Tubal ligation
should be confirmed with medical records of the actual procedure.
-
12. 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):
1. Agrees to follow contraceptive guidance throughout the study as per protocol.
2. 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.
3. 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:
1. Subjects have tumors that have actionable genomic alterations with approved
targeted therapy in first line setting are not eligible to participate.
2. Subjects are not eligible if they received any prior therapy (SOC or
investigational) for advanced or metastatic disease including chemotherapy,
targeted therapy, or immunotherapy of any kind such as the following:
pembrolizumab, an anti-PD(L)-1 or anti-programmed death ligand 2 (PD-L2) agent,
or an agent directed to another stimulatory or co-inhibitory T-cell receptor
(e.g., CTLA4, OX40 (Tumor necrosis factor receptor superfamily, member 4),
CD137(Tumor necrosis factor receptor superfamily member 9)).
- 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.
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study drug(s).
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.
- Has not recovered to ≤ Grade 1 or to baseline from prior cancer therapy toxicity.
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.
- Has not adequately recovered from major surgery and/or complications from the
procedure prior to the first dose of study drug(s).
- Pulmonary hemorrhage or hemoptysis > 2.5 mL blood within 6 weeks of screening (or
within 2 weeks if the source of bleeding is treated).
- Received a live or live-attenuated vaccine within 30 days prior to the first dose of
study drug(s). Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever,
rabies, Bacille Calmette-Guerin, and typhoid vaccine. Seasonal influenza vaccines
are generally killed virus vaccines and are permitted; however, intranasal influenza
vaccines (e.g., Flu-Mist®) are live-attenuated vaccines and are not allowed.
Note: The administration of killed vaccines, mRNA vaccines, and DNA vaccines is allowed.
- Has an active diagnosis of immunodeficiency or is receiving systemic steroid therapy
(exceeding 10 mg daily of prednisone equivalent) or has received any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug(s).
- Has active autoimmune disease which required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive
drugs).
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.
- Known additional malignancy that is progressing or has required active treatment
within the past 2 years.
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:
1. Are radiologically stable (no progression) for at least 4 weeks as documented
by screening computed tomography (CT) or magnetic resonance imaging (MRI) scan.
2. Clinically stable.
3. No evidence of new or enlarging brain metastases. Does not require steroids for
at least 14 days before starting first dose of study drug(s) (anticonvulsants
at a stable dose are allowed). Low dose steroids equivalent of prednisone ≤ 10
mg orally once a day is allowed.
4. No history of intracranial or spinal cord hemorrhage.
5. No evidence of significant vasogenic edema.
- 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.
- A history or current evidence of any severe acute or chronic medical or psychiatric
condition that requires treatment, or laboratory abnormality that might confound the
results of the study, interfere with the subject's participation for the full
duration of the study, or is not in the best interest of the subject, in the opinion
of the Principal Investigator (PI; also referred to as Investigator). Examples
include, but are not limited to, active uncontrolled infection (including
tuberculosis [TB]) requiring systemic therapy, transfusion dependent anemia, recent
(within 90 days) stroke or myocardial infarction, unstable angina, uncontrolled
major seizure disorder, unstable spinal cord compression, superior vena cava
syndrome, symptomatic congestive heart failure (New York Heart Association class ≥
III/IV), and recent severe Coronavirus disease 2019 (COVID-19).
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.
- Systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥100 mmHg.
- Has a corrected QT interval by Fridericia (QTcF) ≥ 470 msec. Note: Apply the
Fridericia QT correction to calculate QTcF using the following formula: QTcF =
QT/RR1/3 where QT = the time between the start of the QRS complex and the end of the
T wave and RR = the time between the start of one QRS complex and the start of the
next QRS complex.
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.
- History or presence of sustained or symptomatic bradycardia (≤ 55 bpm), left bundle
branch block, ventricular arrhythmia excluding premature ventricular contractions,
or uncontrolled ventricular arrhythmia. Subjects with a supraventricular arrhythmia
requiring medical treatment and a normal ventricular rate are eligible.
- Psychological, familial, sociological, or geographical conditions including known
psychiatric or substance abuse disorder that could interfere with the subject's
ability to provide informed consent, comply with the protocol, or interfere with the
interpretation of the study results.
- Inability to swallow oral medication and/or the presence of active gastrointestinal
(GI) disease and/or other GI conditions, including bowel resection, that is expected
to interfere significantly with the absorption, distribution, metabolism, or
excretion of oral SLC-391 therapy.
- Received radiation therapy to the lung that is > 30 Gy within 6 months of the first
dose of study drug(s).
- Had an allogenic tissue, marrow, or solid organ transplant.
- Females who are pregnant or nursing. Note: SLC reserves the right to deny any
subject enrollment based upon potential safety concern(s) or factors that could
confound the study results.
Note: The Investigator or licensed, medically qualified Sub-Investigator must review and
confirm eligibility prior to the first dose of study drug(s).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Community Health Network
Address:
City:
Indianapolis
Zip:
46250
Country:
United States
Status:
Recruiting
Facility:
Name:
Horizon Verdi Oncology
Address:
City:
Lafayette
Zip:
47905
Country:
United States
Status:
Terminated
Facility:
Name:
Karmanos Cancer Center
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Facility:
Name:
Nebraska Cancer Specialists
Address:
City:
Omaha
Zip:
68130
Country:
United States
Status:
Recruiting
Facility:
Name:
Cleveland Clinic
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Facility:
Name:
Stephenson Cancer Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Nashville Oncology Associates
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Facility:
Name:
Cross Cancer Institute
Address:
City:
Edmonton
Country:
Canada
Status:
Recruiting
Facility:
Name:
Juravinski Cancer Centre
Address:
City:
Hamilton
Country:
Canada
Status:
Recruiting
Facility:
Name:
London Regional Cancer Centre
Address:
City:
London
Country:
Canada
Status:
Recruiting
Facility:
Name:
Sunnybrook Health Sciences Centre
Address:
City:
Toronto
Country:
Canada
Status:
Recruiting
Facility:
Name:
Hôpital de la Cité-de-la-Santé
Address:
City:
Laval
Zip:
H7M 3L9
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
Jewish General Hospital
Address:
City:
Montréal
Zip:
H3T 1E2
Country:
Canada
Status:
Not yet recruiting
Start date:
May 31, 2023
Completion date:
September 2028
Lead sponsor:
Agency:
SignalChem Lifesciences Corporation
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
SignalChem Lifesciences Corporation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05860296
