Diffuse Large B Cell Lymphoma, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Hodgkin Lymphoma, Melanoma, Mismatch Repair Deficient or MSI-High Solid Tumors, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Squamous Cell Carcinoma of the Anus, Squamous Cell Carcinoma of the Cervix, Squamous Cell Carcinoma of the Head and Neck, Squamous Cell Carcinoma of the Skin, Urothelial Carcinoma
Conditions
Brief summary
This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-279252 in subjects with advanced solid tumors or lymphomas.
Detailed description
This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-279252 in subjects with advanced solid tumors or lymphomas. The study design consists of Dose Escalation and Dose Expansion Cohorts. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. During dose escalation, two possible schedules for administration of SL-279252 may be explored. The MTD or MAD may be determined for either schedule. Based on accumulating data from the dose escalation phase, including safety, PK, pharmacodynamic and anti-tumor activity, up to two dose expansion cohorts may be opened. The primary objective of the expansion phase is to further refine the safety and tolerability of SL-279252. The expansion cohorts will evaluate one or two doses of SL-279252 using one selected schedule. At the end of dose escalation and dose expansion, safety, PK, anti-tumor activity, and pharmacodynamic data will be reviewed to identify the RP2D.
Interventions
DRUGSL-279252
The investigational product (IP), SL-279252, is a first-in-class agonist redirected checkpoint (ARC) fusion protein (FP) consisting of the extracellular domains of human programmed cell death 1 (PD- 1) and OX40L, linked by a central Fc domain (PD1-Fc-OX40L).
Sponsors
Shattuck Labs, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply. 1. Subject has voluntarily agreed to participate by giving written informed consent in accordance with ICH/GCP guidelines and applicable local regulations. 2. Subject has a histologically confirmed diagnosis of one of the following unresectable locally advanced or metastatic malignancies: melanoma, non-small cell lung cancer (squamous, adeno, or adeno-squamous), urothelial cancer, squamous cell carcinoma of the head and neck, squamous cell cervical cancer, gastric or gastro-esophageal junction adenocarcinoma, squamous cell carcinoma of the anal canal, squamous cell carcinoma of the skin, renal cell cancer, Hodgkin's lymphoma, and microsatellite instability high (MSI-H) or mismatch repair deficient (MMRD) solid tumors excluding CNS malignancies. MSI and MMRD testing results as per institution is acceptable. * Head and neck cancers: Subjects must have primary tumor locations in the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor sites of nasopharynx, maxillary sinus, paranasal, and unknown primary are excluded. * Non-small cell lung cancers: Subjects with a known EGFR sensitizing (activating) mutation or an ALK fusion are excluded. 3. Subject must have received, been intolerant to, or is ineligible for standard therapy (per local guidelines and approvals) or have a malignancy for which there is no approved therapy considered standard of care. 4. Age 18 years and older. 5. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. 6. Has measurable disease by iRECIST (solid tumors) or RECIL 2017 (lymphoma). Refer to Appendix Sections 16.6 and 16.7 for details on criteria of measurable disease. 7. Has life expectancy of greater than 12 weeks. 8. Laboratory values must meet the following criteria. Laboratory parameter Threshold value * Absolute lymphocyte count (ALC) ≥ 0.8 x 109/liter (L) * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support * Platelet count ≥ 50 x 109/L Laboratory parameter Threshold value * Hemoglobin (Hgb) \> 9.0 g/dL with no blood transfusions for at least 5 days prior to D1 of investigational product (IP; SL-279252) * Creatinine clearance (CrCl) ≥ 30 milliliter (mL)/min (modified Cockcroft-Gault) * ALT/AST ≤ 3 x ULN * Total bilirubin ≤ 1.5 x ULN; subjects with isolated indirect hyperbilirubinemia are permitted if direct bilirubin ratio is \<35% and total bilirubin is ≤ 3.0 x ULN * Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) ≥ lower limit of normal (LLN) per institutional threshold. If LLN is not defined for a given institution, then ejection fraction must be ≥50 %. 9. Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of D1 of IP. NOTE: FCBP unless they are surgically sterile (i.e., have undergone a complete hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy or bilateral salpingectomy), have a congenital or acquired condition that prevents childbearing or are naturally postmenopausal for at least 12 consecutive months (see Appendix Section 16.2 for additional details). Documentation of postmenopausal status must be provided. FCBP should use an acceptable method of contraception (see Appendix Section 16.2) to avoid pregnancy during treatment and for 30 days (which exceeds 5 half-lives) after the last dose of IP. FCBP must start using acceptable contraception at least 14 days prior to D1 of IP. 10. Male subjects with female partners must have azoospermia from a prior vasectomy or underlying medical condition or agree to use an acceptable method of contraception during treatment and for 30 days (which exceeds 5 half-lives) after last dose of SL-279252 (see Appendix Section 16.2). Male subjects of reproductive potential must start using acceptable contraception at least 14 days prior to D1 of treatment with SL-279252 as per Appendix Section 16.2. 11. All AEs resulting from prior anti-cancer immunotherapy have resolved (NOTE: exceptions include alopecia, vitiligo, and endocrinopathies adequately treated with hormone replacement). • Subjects that were discontinued from prior PD-1/L1 therapy due to immune-related adverse events are not eligible 12. Recovery from toxicities from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1. (NOTE: Low-grade toxicities (e.g., alopecia, ≤ Grade 2 lymphopenia, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy) may be allowed at the discretion of the investigator if considered clinically insignificant. Please consult the Sponsor Medical Monitor to discuss these cases).
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: 1. Has received more than two prior checkpoint inhibitor containing treatment regimens (regimen refers to either monotherapy or combination immunotherapies) or has had prior treatment with an OX40 agonist. • Prior PD-1/L1 therapy is not required. 2. Refractory to last PD-1/L1 inhibitor-based therapy which is defined as disease progression within 3 months of treatment initiation. • Subjects must have had clinical benefit (stable disease or response) to last PD-1/L1 inhibitor-based therapy for at least three months to be eligible. 3. Any anti-cancer therapy within the time intervals noted below prior to first dose (D1) of SL-279252. Therapy Washout period Chemotherapy 3 weeks Hormonal therapy 3 weeks PD-1/L1 inhibitor and other immunotherapies not otherwise specified 3 weeks Tumor vaccine 4 weeks Cell-based therapy 8 weeks Other mAbs or biologic therapies 3 weeks Major surgery 2 weeks Radiation (except palliative intent which does not require washout) 2 weeks 4. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy is prohibited. Concurrent use of hormones for non-cancer related conditions is acceptable. 5. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of IP with the following exceptions (i.e., the following are allowed during treatment with or within14 days of D1 of IP): * Topical, intranasal, inhaled, ocular, intraarticular corticosteroids * Physiological doses of replacement steroid (e.g., for adrenal insufficiency) provided ≤ 10 mg/day of prednisone or equivalent * Steroid premedication for hypersensitivity reactions (HSRs; e.g., reaction to IV contrast) 6. Receipt of live attenuated vaccine within 28 days of D1 of IP. 7. Active or documented history of autoimmune disease (autoimmune disease does not refer to irAEs; for irAEs see inclusion criteria #11). Exceptions include Type I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism. 8. Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.). 9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 5 days of D1 of IP). 10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal (GI) disease associated with diarrhea within 6 months of D1 of IP. 11. Clinically significant or uncontrolled cardiac disease including any of the following: * Myocarditis * Unstable angina within 6 months from D1 of IP * Acute myocardial infarction within 6 months from D1 of IP * Uncontrolled hypertension * New York Heart Association (NYHA) Class II, III or IV congestive heart failure * Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, second- or third- degree atrioventricular block without a pacemaker, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia requiring therapy) 12. Untreated central nervous system (CNS) or leptomeningeal metastases. Subjects with treated CNS metastases must have completed definitive treatment (radiotherapy and/or surgery) \> 2 weeks prior to D1 of IP and no longer require steroids. 13. Women who are breast feeding. 14. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or compromised ability to provide written informed consent. 15. Another malignancy that requires active therapy and that in the opinion of the investigator and Sponsor would interfere with monitoring of radiologic assessments of response to IP. 16. Has undergone allogeneic stem cell transplantation or organ transplantation. 17. Known history or positive test for human immunodeficiency virus, or positive test for hepatitis B (positive for hepatitis B surface antigen \[HBsAg\]) or hepatitis C virus (\[HCV\]; if HCV antibody (Ab) test is positive check for HCV ribonucleic acid \[RNA\]). * (NOTE: Hepatitis B virus (HBV): Subjects who are hepatitis B core antibody \[HBcAb\] positive, but HBsAg negative are eligible for enrollment. HCV: Subjects who are HCV Ab positive, but HCV RNA negative are eligible for enrollment).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Profile of SL-279252 | From Day 1 to 90 days after Last Dose of SL-279252 | Number of participants with treatment emergent adverse events |
| Maximum Tolerated Dose (MTD) of SL-279252 | From Day 1 to Day 21 (Schedule 1) or Day 28 (Schedule 2) | Number of participants with dose limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity to SL-279252 | Approximately 32 months | Number of participants with positive anti-drug antibody (ADA) titer, of those who were ADA negative at baseline |
| Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days) | The Cmax is the maximum observed serum concentration of SL-279252 following single and multiple doses |
| Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 and Cycle 2 Day 1 (cycle = 28 days) | The Cmin is the minimum observed serum concentration of SL-279252 following single and multiple doses |
| Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days) | The Tmax is the time at which the maximum concentration of SL-279252 is observed following single and multiple doses |
| Recommended Phase 2 Dose for SL-279252 | Approximately 32 months | Based on review of all data, including safety, tolerability, PK, antitumor activity, and PD effects |
| Terminal Half Life (t1/2) | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days) | The t1/2 elimination half-life of SL-279252 |
| Clearance | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days) | Clearance of SL-279252 |
| Volume of Distribution | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days) | Volume of distribution of SL-279252 |
| Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days) | The AUC is the area under the serum concentration time curve following single and multiple doses of SL-279252. AUC (0-inf; from time 0 to infinity) is reported for C1D1 and C2D1 (Schedule 1 only); AUC (tau; over a dosing interval) is reported for C1D15 and C2D1 (Schedule 2 only). |
| Overall Response Rate of SL-279252 | Approximately 32 months | Objective response rate per immune response evaluation criteria in solid tumors (iRECIST) for solid tumors |
Countries
Belgium, Canada, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SL-279252 (0.0001 mg/kg S1) 0.0001 mg/kg of IV SL-279252 (Schedule 1) | 1 |
| SL-279252 (0.001 mg/kg S1) 0.001 mg/kg of IV SL-279252 (Schedule 1) | 1 |
| SL-279252 (0.003 mg/kg S1) 0.003 mg/kg of IV SL-279252 (Schedule 1) | 2 |
| SL-279252 (0.01 mg/kg S1) 0.01 mg/kg of IV SL-279252 (Schedule 1) | 1 |
| SL-279252 (0.03 mg/kg S1) 0.03 mg/kg of IV SL-279252 (Schedule 1) | 2 |
| SL-279252 (0.1 mg/kg S1) 0.1 mg/kg of IV SL-279252 (Schedule 1) | 3 |
| SL-279252 (0.3 mg/kg S1) 0.3 mg/kg of IV SL-279252 (Schedule 1) | 4 |
| SL-279252 (1.0 mg/kg S1) 1.0 mg/kg of IV SL-279252 (Schedule 1) | 6 |
| SL-279252 (3.0 mg/kg S1) 3.0 mg/kg of IV SL-279252 (Schedule 1) | 6 |
| SL-279252 (6.0 mg/kg S1) 6.0 mg/kg of IV SL-279252 (Schedule 1) | 4 |
| SL-279252 (12.0 mg/kg S1) 12.0 mg/kg of IV SL-279252 (Schedule 1) | 4 |
| SL-279252 (24.0 mg/kg S1) 24.0 mg/kg of IV SL-279252 (Schedule 1) | 2 |
| SL-279252 (0.3 mg/kg S2) 0.3 mg/kg of IV SL-279252 (Schedule 2) | 4 |
| SL-279252 (1.0 mg/kg S2) 1.0 mg/kg of IV SL-279252 (Schedule 2) | 6 |
| SL-279252 (3.0 mg/kg S2) 3.0 mg/kg of IV SL-279252 (Schedule 2) | 3 |
| Total | 49 |
Baseline characteristics
| Characteristic | SL-279252 (0.001 mg/kg S1) | SL-279252 (0.003 mg/kg S1) | SL-279252 (0.01 mg/kg S1) | SL-279252 (0.03 mg/kg S1) | SL-279252 (0.1 mg/kg S1) | SL-279252 (0.3 mg/kg S1) | SL-279252 (1.0 mg/kg S1) | SL-279252 (3.0 mg/kg S1) | SL-279252 (0.0001 mg/kg S1) | SL-279252 (6.0 mg/kg S1) | SL-279252 (12.0 mg/kg S1) | SL-279252 (24.0 mg/kg S1) | SL-279252 (0.3 mg/kg S2) | SL-279252 (1.0 mg/kg S2) | SL-279252 (3.0 mg/kg S2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 70.0 years | 51.5 years | 58.0 years | 48.5 years | 68.0 years | 74.5 years | 61.5 years | 53.0 years | 68.0 years | 65.0 years | 65.0 years | 66.5 years | 68.5 years | 60.0 years | 62.0 years | 64.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 6 Participants | 3 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 1 Participants | 4 Participants | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 2 Participants | 44 Participants |
| Region of Enrollment Belgium | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 5 participants |
| Region of Enrollment Canada | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 1 participants | 1 participants | 1 participants | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 2 participants | 2 participants | 11 participants |
| Region of Enrollment Spain | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 2 participants | 2 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 3 participants | 1 participants | 10 participants |
| Region of Enrollment United States | 1 participants | 1 participants | 0 participants | 2 participants | 3 participants | 1 participants | 2 participants | 3 participants | 1 participants | 1 participants | 4 participants | 1 participants | 3 participants | 0 participants | 0 participants | 23 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 4 Participants | 4 Participants | 1 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 | 2 / 2 | 1 / 1 | 0 / 2 | 3 / 3 | 4 / 4 | 4 / 6 | 5 / 6 | 4 / 4 | 2 / 4 | 0 / 2 | 2 / 4 | 5 / 6 | 3 / 3 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 2 / 2 | 1 / 1 | 2 / 2 | 3 / 3 | 4 / 4 | 4 / 6 | 6 / 6 | 3 / 4 | 4 / 4 | 2 / 2 | 4 / 4 | 5 / 6 | 3 / 3 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 | 0 / 2 | 0 / 1 | 0 / 2 | 1 / 3 | 1 / 4 | 3 / 6 | 1 / 6 | 1 / 4 | 0 / 4 | 1 / 2 | 0 / 4 | 2 / 6 | 1 / 3 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of SL-279252
Number of participants with dose limiting toxicities (DLTs)
Time frame: From Day 1 to Day 21 (Schedule 1) or Day 28 (Schedule 2)
Population: DLT evaluable population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (0.001 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (0.003 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (0.01 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (0.03 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (0.1 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (0.3 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (1.0 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (3.0 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (6.0 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (12.0 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (24.0 mg/kg S1) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (0.3 mg/kg S2) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (1.0 mg/kg S2) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
| SL-279252 (3.0 mg/kg S2) | Maximum Tolerated Dose (MTD) of SL-279252 | 0 Participants |
Primary
Safety Profile of SL-279252
Number of participants with treatment emergent adverse events
Time frame: From Day 1 to 90 days after Last Dose of SL-279252
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Safety Profile of SL-279252 | 1 Participants |
| SL-279252 (0.001 mg/kg S1) | Safety Profile of SL-279252 | 1 Participants |
| SL-279252 (0.003 mg/kg S1) | Safety Profile of SL-279252 | 2 Participants |
| SL-279252 (0.01 mg/kg S1) | Safety Profile of SL-279252 | 1 Participants |
| SL-279252 (0.03 mg/kg S1) | Safety Profile of SL-279252 | 2 Participants |
| SL-279252 (0.1 mg/kg S1) | Safety Profile of SL-279252 | 3 Participants |
| SL-279252 (0.3 mg/kg S1) | Safety Profile of SL-279252 | 4 Participants |
| SL-279252 (1.0 mg/kg S1) | Safety Profile of SL-279252 | 5 Participants |
| SL-279252 (3.0 mg/kg S1) | Safety Profile of SL-279252 | 6 Participants |
| SL-279252 (6.0 mg/kg S1) | Safety Profile of SL-279252 | 3 Participants |
| SL-279252 (12.0 mg/kg S1) | Safety Profile of SL-279252 | 4 Participants |
| SL-279252 (24.0 mg/kg S1) | Safety Profile of SL-279252 | 2 Participants |
| SL-279252 (0.3 mg/kg S2) | Safety Profile of SL-279252 | 4 Participants |
| SL-279252 (1.0 mg/kg S2) | Safety Profile of SL-279252 | 5 Participants |
| SL-279252 (3.0 mg/kg S2) | Safety Profile of SL-279252 | 3 Participants |
Secondary
Area Under the Serum Concentration-time Curve (AUC)
The AUC is the area under the serum concentration time curve following single and multiple doses of SL-279252. AUC (0-inf; from time 0 to infinity) is reported for C1D1 and C2D1 (Schedule 1 only); AUC (tau; over a dosing interval) is reported for C1D15 and C2D1 (Schedule 2 only).
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days)
Population: PK Population - number analyzed may be less than the number of participants in a given cohort if samples were below the limit of quantitation or not available for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | NA hours*ng/mL | — |
| SL-279252 (0.0001 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | NA hours*ng/mL | — |
| SL-279252 (0.0001 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | NA hours*ng/mL | — |
| SL-279252 (0.001 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | NA hours*ng/mL | — |
| SL-279252 (0.001 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | NA hours*ng/mL | — |
| SL-279252 (0.001 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | NA hours*ng/mL | — |
| SL-279252 (0.003 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | NA hours*ng/mL | — |
| SL-279252 (0.003 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 56.6 hours*ng/mL | Geometric Coefficient of Variation 77.5 |
| SL-279252 (0.003 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 68.8 hours*ng/mL | — |
| SL-279252 (0.01 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | NA hours*ng/mL | — |
| SL-279252 (0.01 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | NA hours*ng/mL | — |
| SL-279252 (0.03 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 804 hours*ng/mL | — |
| SL-279252 (0.03 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | NA hours*ng/mL | — |
| SL-279252 (0.03 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | NA hours*ng/mL | — |
| SL-279252 (0.1 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | 3240 hours*ng/mL | Geometric Coefficient of Variation 35.7 |
| SL-279252 (0.1 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 2960 hours*ng/mL | Geometric Coefficient of Variation 40.1 |
| SL-279252 (0.1 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 3410 hours*ng/mL | Geometric Coefficient of Variation 47.4 |
| SL-279252 (0.3 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 2 only) | 11500 hours*ng/mL | Geometric Coefficient of Variation 16.1 |
| SL-279252 (0.3 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 10900 hours*ng/mL | Geometric Coefficient of Variation 39.2 |
| SL-279252 (0.3 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 11600 hours*ng/mL | Geometric Coefficient of Variation 43.5 |
| SL-279252 (0.3 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | 10800 hours*ng/mL | Geometric Coefficient of Variation 43.7 |
| SL-279252 (1.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 40800 hours*ng/mL | Geometric Coefficient of Variation 38.9 |
| SL-279252 (1.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 38800 hours*ng/mL | Geometric Coefficient of Variation 32.7 |
| SL-279252 (1.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | 36800 hours*ng/mL | Geometric Coefficient of Variation 24.1 |
| SL-279252 (1.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 2 only) | 33600 hours*ng/mL | Geometric Coefficient of Variation 58.5 |
| SL-279252 (3.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 130000 hours*ng/mL | Geometric Coefficient of Variation 40.5 |
| SL-279252 (3.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 2 only) | 145000 hours*ng/mL | Geometric Coefficient of Variation 35.2 |
| SL-279252 (3.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 110000 hours*ng/mL | Geometric Coefficient of Variation 52.9 |
| SL-279252 (3.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | 103000 hours*ng/mL | Geometric Coefficient of Variation 15.3 |
| SL-279252 (6.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 325000 hours*ng/mL | Geometric Coefficient of Variation 31.5 |
| SL-279252 (6.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 353000 hours*ng/mL | Geometric Coefficient of Variation 29.4 |
| SL-279252 (6.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | 388000 hours*ng/mL | Geometric Coefficient of Variation 28.2 |
| SL-279252 (12.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 1100000 hours*ng/mL | Geometric Coefficient of Variation 21.2 |
| SL-279252 (12.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | 1160000 hours*ng/mL | Geometric Coefficient of Variation 29.7 |
| SL-279252 (12.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 1140000 hours*ng/mL | Geometric Coefficient of Variation 48.2 |
| SL-279252 (24.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 (Schedule 1 only) | 1560000 hours*ng/mL | Geometric Coefficient of Variation 15 |
| SL-279252 (24.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 1380000 hours*ng/mL | Geometric Coefficient of Variation 22.4 |
| SL-279252 (24.0 mg/kg S1) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 1390000 hours*ng/mL | Geometric Coefficient of Variation 16.9 |
Secondary
Clearance
Clearance of SL-279252
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days)
Population: PK Population - number analyzed may be less than the number of participants in a given cohort if samples were below the limit of quantitation or not available for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Clearance | Cycle 1 Day 15 | NA liters per hour per kg | — |
| SL-279252 (0.0001 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | NA liters per hour per kg | — |
| SL-279252 (0.0001 mg/kg S1) | Clearance | Cycle 1 Day 1 | NA liters per hour per kg | — |
| SL-279252 (0.001 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | NA liters per hour per kg | — |
| SL-279252 (0.001 mg/kg S1) | Clearance | Cycle 1 Day 15 | NA liters per hour per kg | — |
| SL-279252 (0.001 mg/kg S1) | Clearance | Cycle 1 Day 1 | NA liters per hour per kg | — |
| SL-279252 (0.003 mg/kg S1) | Clearance | Cycle 1 Day 15 | 0.0436 liters per hour per kg | — |
| SL-279252 (0.003 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0530 liters per hour per kg | Geometric Coefficient of Variation 77.5 |
| SL-279252 (0.003 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | NA liters per hour per kg | — |
| SL-279252 (0.01 mg/kg S1) | Clearance | Cycle 1 Day 15 | NA liters per hour per kg | — |
| SL-279252 (0.01 mg/kg S1) | Clearance | Cycle 1 Day 1 | NA liters per hour per kg | — |
| SL-279252 (0.03 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | NA liters per hour per kg | — |
| SL-279252 (0.03 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0373 liters per hour per kg | — |
| SL-279252 (0.03 mg/kg S1) | Clearance | Cycle 1 Day 15 | NA liters per hour per kg | — |
| SL-279252 (0.1 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | 0.0309 liters per hour per kg | Geometric Coefficient of Variation 35.7 |
| SL-279252 (0.1 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0338 liters per hour per kg | Geometric Coefficient of Variation 40.1 |
| SL-279252 (0.1 mg/kg S1) | Clearance | Cycle 1 Day 15 | 0.0293 liters per hour per kg | Geometric Coefficient of Variation 47.4 |
| SL-279252 (0.3 mg/kg S1) | Clearance | Cycle 1 Day 15 | 0.0258 liters per hour per kg | Geometric Coefficient of Variation 43.5 |
| SL-279252 (0.3 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0274 liters per hour per kg | Geometric Coefficient of Variation 39.2 |
| SL-279252 (0.3 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | 0.0277 liters per hour per kg | Geometric Coefficient of Variation 43.7 |
| SL-279252 (0.3 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 2 only) | 0.0261 liters per hour per kg | Geometric Coefficient of Variation 16.1 |
| SL-279252 (1.0 mg/kg S1) | Clearance | Cycle 1 Day 15 | 0.0245 liters per hour per kg | Geometric Coefficient of Variation 38.9 |
| SL-279252 (1.0 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0258 liters per hour per kg | Geometric Coefficient of Variation 32.7 |
| SL-279252 (1.0 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 2 only) | 0.0298 liters per hour per kg | Geometric Coefficient of Variation 58.5 |
| SL-279252 (1.0 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | 0.0272 liters per hour per kg | Geometric Coefficient of Variation 24.1 |
| SL-279252 (3.0 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 2 only) | 0.0207 liters per hour per kg | Geometric Coefficient of Variation 35.2 |
| SL-279252 (3.0 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0272 liters per hour per kg | Geometric Coefficient of Variation 52.9 |
| SL-279252 (3.0 mg/kg S1) | Clearance | Cycle 1 Day 15 | 0.0231 liters per hour per kg | Geometric Coefficient of Variation 40.5 |
| SL-279252 (3.0 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | 0.0291 liters per hour per kg | Geometric Coefficient of Variation 15.3 |
| SL-279252 (6.0 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0170 liters per hour per kg | Geometric Coefficient of Variation 29.4 |
| SL-279252 (6.0 mg/kg S1) | Clearance | Cycle 1 Day 15 | 0.0184 liters per hour per kg | Geometric Coefficient of Variation 31.5 |
| SL-279252 (6.0 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | 0.0155 liters per hour per kg | Geometric Coefficient of Variation 28.2 |
| SL-279252 (12.0 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0106 liters per hour per kg | Geometric Coefficient of Variation 48.2 |
| SL-279252 (12.0 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | 0.0103 liters per hour per kg | Geometric Coefficient of Variation 29.7 |
| SL-279252 (12.0 mg/kg S1) | Clearance | Cycle 1 Day 15 | 0.0109 liters per hour per kg | Geometric Coefficient of Variation 21.2 |
| SL-279252 (24.0 mg/kg S1) | Clearance | Cycle 1 Day 1 | 0.0174 liters per hour per kg | Geometric Coefficient of Variation 22.4 |
| SL-279252 (24.0 mg/kg S1) | Clearance | Cycle 1 Day 15 | 0.0172 liters per hour per kg | Geometric Coefficient of Variation 16.9 |
| SL-279252 (24.0 mg/kg S1) | Clearance | Cycle 2 Day 1 (Schedule 1 only) | 0.0154 liters per hour per kg | Geometric Coefficient of Variation 15 |
Secondary
Immunogenicity to SL-279252
Number of participants with positive anti-drug antibody (ADA) titer, of those who were ADA negative at baseline
Time frame: Approximately 32 months
Population: For arms 0.0001 and 0.001 mg/kg of IV SL-279252, there were no subjects who were ADA negative at baseline. For arms 12.0 and 24.0 mg/kg of IV SL-279252, ADA samples were not collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Immunogenicity to SL-279252 | 0 Participants |
| SL-279252 (0.001 mg/kg S1) | Immunogenicity to SL-279252 | 0 Participants |
| SL-279252 (0.003 mg/kg S1) | Immunogenicity to SL-279252 | 0 Participants |
| SL-279252 (0.01 mg/kg S1) | Immunogenicity to SL-279252 | 1 Participants |
| SL-279252 (0.03 mg/kg S1) | Immunogenicity to SL-279252 | 1 Participants |
| SL-279252 (0.1 mg/kg S1) | Immunogenicity to SL-279252 | 2 Participants |
| SL-279252 (0.3 mg/kg S1) | Immunogenicity to SL-279252 | 1 Participants |
| SL-279252 (1.0 mg/kg S1) | Immunogenicity to SL-279252 | 1 Participants |
| SL-279252 (3.0 mg/kg S1) | Immunogenicity to SL-279252 | 3 Participants |
| SL-279252 (6.0 mg/kg S1) | Immunogenicity to SL-279252 | 1 Participants |
| SL-279252 (12.0 mg/kg S1) | Immunogenicity to SL-279252 | 0 Participants |
| SL-279252 (24.0 mg/kg S1) | Immunogenicity to SL-279252 | 0 Participants |
| SL-279252 (0.3 mg/kg S2) | Immunogenicity to SL-279252 | 1 Participants |
| SL-279252 (1.0 mg/kg S2) | Immunogenicity to SL-279252 | 3 Participants |
| SL-279252 (3.0 mg/kg S2) | Immunogenicity to SL-279252 | 3 Participants |
Secondary
Maximum Serum Concentration (Cmax) of SL-279252
The Cmax is the maximum observed serum concentration of SL-279252 following single and multiple doses
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days)
Population: PK Population - number analyzed may be less than the number of participants in a given cohort if samples were not available for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | NA ng/mL | — |
| SL-279252 (0.0001 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | NA ng/mL | — |
| SL-279252 (0.0001 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | NA ng/mL | — |
| SL-279252 (0.001 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 3.75 ng/mL | — |
| SL-279252 (0.001 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | NA ng/mL | — |
| SL-279252 (0.001 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 3.22 ng/mL | — |
| SL-279252 (0.003 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 50.6 ng/mL | Geometric Coefficient of Variation 49.2 |
| SL-279252 (0.003 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 30.8 ng/mL | Geometric Coefficient of Variation 4.6 |
| SL-279252 (0.003 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 19.5 ng/mL | — |
| SL-279252 (0.01 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 93.4 ng/mL | — |
| SL-279252 (0.01 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | NA ng/mL | — |
| SL-279252 (0.03 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 360 ng/mL | Geometric Coefficient of Variation 6.09 |
| SL-279252 (0.03 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 408 ng/mL | Geometric Coefficient of Variation 13 |
| SL-279252 (0.03 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 427 ng/mL | Geometric Coefficient of Variation 1.82 |
| SL-279252 (0.1 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 734 ng/mL | Geometric Coefficient of Variation 42.9 |
| SL-279252 (0.1 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 1090 ng/mL | Geometric Coefficient of Variation 20.9 |
| SL-279252 (0.1 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 731 ng/mL | Geometric Coefficient of Variation 35.9 |
| SL-279252 (0.3 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 2 only) | 4110 ng/mL | Geometric Coefficient of Variation 13.4 |
| SL-279252 (0.3 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 3580 ng/mL | Geometric Coefficient of Variation 29.6 |
| SL-279252 (0.3 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 2920 ng/mL | Geometric Coefficient of Variation 52.9 |
| SL-279252 (0.3 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 4260 ng/mL | Geometric Coefficient of Variation 24.2 |
| SL-279252 (1.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 10400 ng/mL | Geometric Coefficient of Variation 45.9 |
| SL-279252 (1.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 10200 ng/mL | Geometric Coefficient of Variation 42 |
| SL-279252 (1.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 9760 ng/mL | Geometric Coefficient of Variation 28.4 |
| SL-279252 (1.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 2 only) | 11700 ng/mL | Geometric Coefficient of Variation 36.9 |
| SL-279252 (3.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 26100 ng/mL | Geometric Coefficient of Variation 67 |
| SL-279252 (3.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 2 only) | 38300 ng/mL | Geometric Coefficient of Variation 22.7 |
| SL-279252 (3.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 28100 ng/mL | Geometric Coefficient of Variation 43 |
| SL-279252 (3.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 25400 ng/mL | Geometric Coefficient of Variation 103 |
| SL-279252 (6.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 75300 ng/mL | Geometric Coefficient of Variation 21.5 |
| SL-279252 (6.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 83600 ng/mL | Geometric Coefficient of Variation 26.3 |
| SL-279252 (6.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 94100 ng/mL | Geometric Coefficient of Variation 15.6 |
| SL-279252 (12.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 277000 ng/mL | Geometric Coefficient of Variation 10.5 |
| SL-279252 (12.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 236000 ng/mL | Geometric Coefficient of Variation 25.8 |
| SL-279252 (12.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 248000 ng/mL | Geometric Coefficient of Variation 34.7 |
| SL-279252 (24.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 2 Day 1 (Schedule 1 only) | 355000 ng/mL | Geometric Coefficient of Variation 7.97 |
| SL-279252 (24.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 1 | 320000 ng/mL | Geometric Coefficient of Variation 16 |
| SL-279252 (24.0 mg/kg S1) | Maximum Serum Concentration (Cmax) of SL-279252 | Cycle 1 Day 15 | 349000 ng/mL | Geometric Coefficient of Variation 4.05 |
Secondary
Minimum Serum Concentration (Cmin) of SL-279252
The Cmin is the minimum observed serum concentration of SL-279252 following single and multiple doses
Time frame: Cycle 1 Day 15 and Cycle 2 Day 1 (cycle = 28 days)
Population: PK Population - number analyzed may be less than the number of participants in a given cohort if samples were below the limit of quantitation or not available for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | NA ng/mL | — |
| SL-279252 (0.001 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | NA ng/mL | — |
| SL-279252 (0.003 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | NA ng/mL | — |
| SL-279252 (0.01 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | NA ng/mL | — |
| SL-279252 (0.03 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | NA ng/mL | — |
| SL-279252 (0.1 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | NA ng/mL | — |
| SL-279252 (0.3 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | 1.03 ng/mL | Geometric Coefficient of Variation 71.9 |
| SL-279252 (0.3 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 2 Day 1 (Schedule 2 only) | 1.12 ng/mL | Geometric Coefficient of Variation 75.2 |
| SL-279252 (1.0 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | 3.77 ng/mL | Geometric Coefficient of Variation 56.5 |
| SL-279252 (1.0 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 2 Day 1 (Schedule 2 only) | NA ng/mL | — |
| SL-279252 (3.0 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | 10.4 ng/mL | Geometric Coefficient of Variation 124 |
| SL-279252 (3.0 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 2 Day 1 (Schedule 2 only) | 11.9 ng/mL | Geometric Coefficient of Variation 164 |
| SL-279252 (6.0 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | 29.0 ng/mL | Geometric Coefficient of Variation 43 |
| SL-279252 (12.0 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | 90.7 ng/mL | Geometric Coefficient of Variation 100 |
| SL-279252 (24.0 mg/kg S1) | Minimum Serum Concentration (Cmin) of SL-279252 | Cycle 1 Day 15 | 12.7 ng/mL | — |
Secondary
Overall Response Rate of SL-279252
Objective response rate per immune response evaluation criteria in solid tumors (iRECIST) for solid tumors
Time frame: Approximately 32 months
Population: All treated population with solid tumors
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (0.001 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (0.003 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (0.01 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (0.03 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (0.1 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (0.3 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (1.0 mg/kg S1) | Overall Response Rate of SL-279252 | 1 Participants |
| SL-279252 (3.0 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (6.0 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (12.0 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (24.0 mg/kg S1) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (0.3 mg/kg S2) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (1.0 mg/kg S2) | Overall Response Rate of SL-279252 | 0 Participants |
| SL-279252 (3.0 mg/kg S2) | Overall Response Rate of SL-279252 | 0 Participants |
Secondary
Recommended Phase 2 Dose for SL-279252
Based on review of all data, including safety, tolerability, PK, antitumor activity, and PD effects
Time frame: Approximately 32 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Recommended Phase 2 Dose for SL-279252 | NA mg/kg |
Secondary
Terminal Half Life (t1/2)
The t1/2 elimination half-life of SL-279252
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days)
Population: PK Population - number analyzed may be less than the number of participants in a given cohort if samples were below the limit of quantitation or not available for analysis. Not estimable based on subjects' concentration profiles, including values below the limit of quantification
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | NA hours |
| SL-279252 (0.0001 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | NA hours |
| SL-279252 (0.0001 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | NA hours |
| SL-279252 (0.001 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | NA hours |
| SL-279252 (0.001 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | NA hours |
| SL-279252 (0.001 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 2.69 hours |
| SL-279252 (0.003 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | NA hours |
| SL-279252 (0.003 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | 5.74 hours |
| SL-279252 (0.003 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 4.36 hours |
| SL-279252 (0.01 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | NA hours |
| SL-279252 (0.01 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | NA hours |
| SL-279252 (0.03 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 1.23 hours |
| SL-279252 (0.03 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | NA hours |
| SL-279252 (0.03 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | NA hours |
| SL-279252 (0.1 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | 5.30 hours |
| SL-279252 (0.1 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 25.2 hours |
| SL-279252 (0.1 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | 5.30 hours |
| SL-279252 (0.3 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | 5.22 hours |
| SL-279252 (0.3 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | 5.87 hours |
| SL-279252 (0.3 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 2 only) | 4.48 hours |
| SL-279252 (0.3 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 23.4 hours |
| SL-279252 (1.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 22.6 hours |
| SL-279252 (1.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | 6.00 hours |
| SL-279252 (1.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | 5.98 hours |
| SL-279252 (1.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 2 only) | 5.09 hours |
| SL-279252 (3.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | 6.14 hours |
| SL-279252 (3.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 2 only) | 5.10 hours |
| SL-279252 (3.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 22.4 hours |
| SL-279252 (3.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | 5.48 hours |
| SL-279252 (6.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | 6.48 hours |
| SL-279252 (6.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 22.9 hours |
| SL-279252 (6.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | 5.32 hours |
| SL-279252 (12.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | 4.86 hours |
| SL-279252 (12.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | 4.71 hours |
| SL-279252 (12.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 20.0 hours |
| SL-279252 (24.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 2 Day 1 (Schedule 1 only) | 3.78 hours |
| SL-279252 (24.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 1 | 14.4 hours |
| SL-279252 (24.0 mg/kg S1) | Terminal Half Life (t1/2) | Cycle 1 Day 15 | 4.13 hours |
Secondary
Time at Which Maximum Concentration of SL-279252 is Observed (Tmax)
The Tmax is the time at which the maximum concentration of SL-279252 is observed following single and multiple doses
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days)
Population: PK Population - number analyzed may be less than the number of participants in a given cohort if samples were below the limit of quantitation or not available for analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | NA hours |
| SL-279252 (0.0001 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | NA hours |
| SL-279252 (0.0001 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | NA hours |
| SL-279252 (0.001 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 0.42 hours |
| SL-279252 (0.001 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | NA hours |
| SL-279252 (0.001 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 0.17 hours |
| SL-279252 (0.003 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 0.38 hours |
| SL-279252 (0.003 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 1.89 hours |
| SL-279252 (0.003 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 0.33 hours |
| SL-279252 (0.01 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 0.72 hours |
| SL-279252 (0.01 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | NA hours |
| SL-279252 (0.03 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 0.50 hours |
| SL-279252 (0.03 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 0.55 hours |
| SL-279252 (0.03 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 0.78 hours |
| SL-279252 (0.1 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 0.55 hours |
| SL-279252 (0.1 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 0.58 hours |
| SL-279252 (0.1 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 0.50 hours |
| SL-279252 (0.3 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 2 only) | 0.70 hours |
| SL-279252 (0.3 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 0.53 hours |
| SL-279252 (0.3 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 0.50 hours |
| SL-279252 (0.3 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 0.54 hours |
| SL-279252 (1.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 1.00 hours |
| SL-279252 (1.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 1.05 hours |
| SL-279252 (1.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 1.05 hours |
| SL-279252 (1.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 2 only) | 1.04 hours |
| SL-279252 (3.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 1.00 hours |
| SL-279252 (3.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 2 only) | 1.03 hours |
| SL-279252 (3.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 1.05 hours |
| SL-279252 (3.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 1.38 hours |
| SL-279252 (6.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 1.00 hours |
| SL-279252 (6.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 0.86 hours |
| SL-279252 (6.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 1.00 hours |
| SL-279252 (12.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 1.00 hours |
| SL-279252 (12.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 1.17 hours |
| SL-279252 (12.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 1.40 hours |
| SL-279252 (24.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 2 Day 1 (Schedule 1 only) | 1.08 hours |
| SL-279252 (24.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 1 | 1.16 hours |
| SL-279252 (24.0 mg/kg S1) | Time at Which Maximum Concentration of SL-279252 is Observed (Tmax) | Cycle 1 Day 15 | 1.00 hours |
Secondary
Volume of Distribution
Volume of distribution of SL-279252
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (cycle = 28 days)
Population: PK Population - number analyzed may be less than the number of participants in a given cohort if samples were below the limit of quantitation or not available for analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SL-279252 (0.0001 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | NA liters per kg | — |
| SL-279252 (0.0001 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | NA liters per kg | — |
| SL-279252 (0.001 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | NA liters per kg | — |
| SL-279252 (0.001 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | NA liters per kg | — |
| SL-279252 (0.003 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | NA liters per kg | — |
| SL-279252 (0.003 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.291 liters per kg | Geometric Coefficient of Variation 6.92 |
| SL-279252 (0.01 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | NA liters per kg | — |
| SL-279252 (0.03 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.0664 liters per kg | — |
| SL-279252 (0.03 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | NA liters per kg | — |
| SL-279252 (0.1 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.576 liters per kg | Geometric Coefficient of Variation 144 |
| SL-279252 (0.1 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | 0.200 liters per kg | Geometric Coefficient of Variation 46.3 |
| SL-279252 (0.3 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | 0.207 liters per kg | Geometric Coefficient of Variation 37.1 |
| SL-279252 (0.3 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.894 liters per kg | Geometric Coefficient of Variation 38 |
| SL-279252 (0.3 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 2 only) | 0.178 liters per kg | Geometric Coefficient of Variation 8.63 |
| SL-279252 (1.0 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.797 liters per kg | Geometric Coefficient of Variation 31.8 |
| SL-279252 (1.0 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 2 only) | 0.189 liters per kg | Geometric Coefficient of Variation 30.4 |
| SL-279252 (1.0 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | 0.237 liters per kg | Geometric Coefficient of Variation 23.7 |
| SL-279252 (3.0 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.939 liters per kg | Geometric Coefficient of Variation 52.8 |
| SL-279252 (3.0 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 2 only) | 0.149 liters per kg | Geometric Coefficient of Variation 47.1 |
| SL-279252 (3.0 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | 0.229 liters per kg | Geometric Coefficient of Variation 12.5 |
| SL-279252 (6.0 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | 0.118 liters per kg | Geometric Coefficient of Variation 9.5 |
| SL-279252 (6.0 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.562 liters per kg | Geometric Coefficient of Variation 33.8 |
| SL-279252 (12.0 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | 0.0730 liters per kg | Geometric Coefficient of Variation 20.5 |
| SL-279252 (12.0 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.281 liters per kg | Geometric Coefficient of Variation 64.8 |
| SL-279252 (24.0 mg/kg S1) | Volume of Distribution | Cycle 2 Day 1 (Schedule 1 only) | 0.0834 liters per kg | Geometric Coefficient of Variation 32.3 |
| SL-279252 (24.0 mg/kg S1) | Volume of Distribution | Cycle 1 Day 1 | 0.348 liters per kg | Geometric Coefficient of Variation 17.4 |