Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Carcinoma
Conditions
Brief summary
This is a Phase 1 first in human, open label, multi-center, dose escalation study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in subjects with ovarian cancer.
Detailed description
This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and pharmacodynamic effects of SL-172154 and identify the dose and schedule i.e., recommended Phase 2 dose for future development (RP2D). Subjects eligible for enrollment are required to have platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers. The study design consists of dose escalation cohorts, an optional pharmacodynamic cohort, and an optional dose expansion cohort. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. The study may also enroll a pharmacodynamic cohort to obtain additional pharmacodynamic data at one or more dose levels that have completed evaluation for safety without exceeding the maximum tolerated dose (MTD). Subjects enrolled in the pharmacodynamic cohort will not inform dose escalation decisions. A dose expansion cohort may be opened to further characterize safety, tolerability, PK, anti-tumor activity, and pharmacodynamic data to inform the selection of a RP2D.
Interventions
DRUGSL-172154
The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.
Sponsors
Shattuck Labs, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
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 must have a histologically confirmed diagnosis of an unresectable, locally advanced or metastatic ovarian cancer, or primary peritoneal cancer or fallopian tube cancer. 3. Subjects must be refractory or intolerant to existing therapy(ies) known to provide clinical benefit for their condition. Subject must have received platinum-based therapies, and should not be eligible for further platinum therapy, or should be intolerant to such therapy. Subjects with HRD positive disease may participate if they have received prior polyadenosine diphosphate ribose polymerase (PARP) inhibitor therapy given alone or with bevacizumab. 4. Subjects should not be primary platinum refractory as defined by progressing during or within 1 month of upfront platinum therapy. 5. Has measurable disease by RECIST v1.1 using radiologic assessment. 6. Subject age is 18 years and older. 7. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 8. Has life expectancy of greater than 12 weeks. 9. Has adequate organ function. 10. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of D1 of IP. 11. Recovery from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1. 12. Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies), unless there is excessive risk as determined by the investigator.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: 1. Prior treatment with an anti-CD47 or anti-SIRPα targeting agent or a CD40 agonist. 2. Any anti-cancer therapy within the washout period prior to first dose (D1) of SL-172154. 3. Concurrent chemotherapy, immunotherapy, biologic or hormonal/hormonal suppression therapy for cancer treatment is prohibited. Concurrent use of hormones for non-cancer related conditions is acceptable. 4. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of SL-172154 treatment. 5. Receipt of live attenuated vaccine within 28 days of D1 of IP. 6. Active or documented history of autoimmune disease. Exceptions include controlled Type I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism. 7. Hypersensitivity to the active drug substance or to any of the excipients for the agent to be administered or subjects with known hypersensitivity to Chinese hamster ovary cell products. 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 disease associated with diarrhea within 6 months of D1 of IP. 11. Clinically significant or uncontrolled cardiac/thromboembolic disease. 12. Untreated central nervous system or leptomeningeal metastases. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Profile of SL-172154 | From Day 1 to 90 days after Last Dose of SL-172154 | Number of participants with treatment emergent adverse events |
| Maximum Tolerated Dose (MTD) of SL-172154 | From Day 1 to 90 days after Last Dose of SL-172154 | Number of participants with dose limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity to SL-172154 | Approximately 24 months | Number of participants with positive anti-drug antibody (ADA) titer, sustained ADA response (positive ADA in \>/= 2 samples without reverting to negative ADA or positive ADA in the last sample), or persistent ADA response (positive ADA in \>/= 2 samples where the first and last samples are \>/= 16 weeks apart, or positive ADA in the last sample, or only one sample but \< 16 weeks before a negative last sample). |
| Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days) | The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses |
| Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 1 Day 15 and Cycle 2 Day 1 (each cycle = 28 days) | The Cmin is the minimum observed serum concentration of SL-172154 following at least one dose |
| Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days) | The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses |
| Recommended Phase 2 Dose (RP2D) for SL-172154 | Approximately 24 months | Based on review of all data, including safety, tolerability, PK, antitumor activity, and PD effects |
| Terminal Elimination Half-life (t1/2) | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days) | Terminal elimination half-life (t1/2) of SL-172154 |
| Clearance (CL) | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days) | Clearance of SL-172154 |
| Volume of Distribution | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days) | Volume of distribution of SL-172154 |
| Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days) | The AUC is the area under the serum concentration time curve following single and multiple doses of SL-172154. AUC (0-last; from time 0 to the last quantifiable concentration) is reported for C1D1 and AUC (tau; over a dosing interval) is reported for C1D15 and C2D1. |
| Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 | Approximately 24 months | Number of participants with an objective response per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Objective response includes complete response (disappearance of all target lesions) and partial response (\>/= 30% decrease in the sum of the longest diameter of target lesions). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SL-172154 (0.1 mg/kg) 0.1 mg/kg of IV SL-172154 (Schedule 1) | 3 |
| SL-172154 (0.3 mg/kg) 0.3 mg/kg of IV SL-172154 (Schedule 1 or Schedule 2) | 6 |
| SL-172154 (1.0 mg/kg) 1.0 mg/kg of IV SL-172154 (Schedule 1) | 4 |
| SL-172154 (3.0 mg/kg) 3.0 mg/kg of IV SL-172154 (Schedule 1 or Schedule 2) | 9 |
| SL-172154 (10.0 mg/kg) 10.0 mg/kg of IV SL-172154 (Schedule 1) | 5 |
| Total | 27 |
Baseline characteristics
| Characteristic | SL-172154 (0.1 mg/kg) | SL-172154 (0.3 mg/kg) | SL-172154 (1.0 mg/kg) | SL-172154 (3.0 mg/kg) | SL-172154 (10.0 mg/kg) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 72.0 years | 65.0 years | 60.5 years | 68.0 years | 67.0 years | 66.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 6 Participants | 2 Participants | 9 Participants | 5 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 2 Participants | 6 Participants | 2 Participants | 8 Participants | 3 Participants | 21 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 4 Participants | 9 Participants | 5 Participants | 27 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 5 / 6 | 3 / 4 | 2 / 9 | 1 / 5 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 4 / 4 | 9 / 9 | 5 / 5 |
| serious Total, serious adverse events | 1 / 3 | 0 / 6 | 1 / 4 | 2 / 9 | 2 / 5 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of SL-172154
Number of participants with dose limiting toxicities (DLTs)
Time frame: From Day 1 to 90 days after Last Dose of SL-172154
Population: DLT evaluable population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SL-172154 (0.1 mg/kg) | Maximum Tolerated Dose (MTD) of SL-172154 | 0 Participants |
| SL-172154 (0.3 mg/kg) | Maximum Tolerated Dose (MTD) of SL-172154 | 0 Participants |
| SL-172154 (1.0 mg/kg) | Maximum Tolerated Dose (MTD) of SL-172154 | 0 Participants |
| SL-172154 (3.0 mg/kg) | Maximum Tolerated Dose (MTD) of SL-172154 | 0 Participants |
| SL-172154 (10.0 mg/kg) | Maximum Tolerated Dose (MTD) of SL-172154 | 1 Participants |
Primary
Safety Profile of SL-172154
Number of participants with treatment emergent adverse events
Time frame: From Day 1 to 90 days after Last Dose of SL-172154
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SL-172154 (0.1 mg/kg) | Safety Profile of SL-172154 | 3 Participants |
| SL-172154 (0.3 mg/kg) | Safety Profile of SL-172154 | 6 Participants |
| SL-172154 (1.0 mg/kg) | Safety Profile of SL-172154 | 4 Participants |
| SL-172154 (3.0 mg/kg) | Safety Profile of SL-172154 | 9 Participants |
| SL-172154 (10.0 mg/kg) | Safety Profile of SL-172154 | 5 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-172154. AUC (0-last; from time 0 to the last quantifiable concentration) is reported for C1D1 and AUC (tau; over a dosing interval) is reported for C1D15 and C2D1.
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SL-172154 (0.1 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | NA hours*ng/mL | — |
| SL-172154 (0.1 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 | NA hours*ng/mL | — |
| SL-172154 (0.1 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | NA hours*ng/mL | — |
| SL-172154 (0.3 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | NA hours*ng/mL | — |
| SL-172154 (0.3 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 143.54 hours*ng/mL | Geometric Coefficient of Variation 7.74 |
| SL-172154 (0.3 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 | NA hours*ng/mL | — |
| SL-172154 (1.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | NA hours*ng/mL | — |
| SL-172154 (1.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 639.40 hours*ng/mL | Geometric Coefficient of Variation 18.47 |
| SL-172154 (1.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 | NA hours*ng/mL | — |
| SL-172154 (3.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 7062.14 hours*ng/mL | Geometric Coefficient of Variation 81.59 |
| SL-172154 (3.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 | 6103.60 hours*ng/mL | Geometric Coefficient of Variation 130.09 |
| SL-172154 (3.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 13030.1 hours*ng/mL | Geometric Coefficient of Variation 27.31 |
| SL-172154 (10.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 15 | 133015.0 hours*ng/mL | — |
| SL-172154 (10.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 1 Day 1 | 200095.11 hours*ng/mL | Geometric Coefficient of Variation 78.74 |
| SL-172154 (10.0 mg/kg) | Area Under the Serum Concentration-time Curve (AUC) | Cycle 2 Day 1 | 236849.02 hours*ng/mL | Geometric Coefficient of Variation 91.9 |
Secondary
Assess Preliminary Evidence of Anti-tumor Activity of SL-172154
Number of participants with an objective response per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Objective response includes complete response (disappearance of all target lesions) and partial response (\>/= 30% decrease in the sum of the longest diameter of target lesions).
Time frame: Approximately 24 months
Population: Response Evaluable Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SL-172154 (0.1 mg/kg) | Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 | 0 Participants |
| SL-172154 (0.3 mg/kg) | Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 | 0 Participants |
| SL-172154 (1.0 mg/kg) | Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 | 0 Participants |
| SL-172154 (3.0 mg/kg) | Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 | 0 Participants |
| SL-172154 (10.0 mg/kg) | Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 | 0 Participants |
Secondary
Clearance (CL)
Clearance of SL-172154
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SL-172154 (0.1 mg/kg) | Clearance (CL) | Cycle 1 Day 1 | NA liters per hour | — |
| SL-172154 (0.1 mg/kg) | Clearance (CL) | Cycle 2 Day 1 | NA liters per hour | — |
| SL-172154 (0.1 mg/kg) | Clearance (CL) | Cycle 1 Day 15 | NA liters per hour | — |
| SL-172154 (0.3 mg/kg) | Clearance (CL) | Cycle 1 Day 15 | NA liters per hour | — |
| SL-172154 (0.3 mg/kg) | Clearance (CL) | Cycle 1 Day 1 | 110.64 liters per hour | — |
| SL-172154 (0.3 mg/kg) | Clearance (CL) | Cycle 2 Day 1 | NA liters per hour | — |
| SL-172154 (1.0 mg/kg) | Clearance (CL) | Cycle 1 Day 1 | 121.22 liters per hour | Standard Deviation 46.305 |
| SL-172154 (1.0 mg/kg) | Clearance (CL) | Cycle 1 Day 15 | NA liters per hour | — |
| SL-172154 (1.0 mg/kg) | Clearance (CL) | Cycle 2 Day 1 | NA liters per hour | — |
| SL-172154 (3.0 mg/kg) | Clearance (CL) | Cycle 1 Day 1 | 35.73 liters per hour | Standard Deviation 25.58 |
| SL-172154 (3.0 mg/kg) | Clearance (CL) | Cycle 2 Day 1 | 44.88 liters per hour | Standard Deviation 48.958 |
| SL-172154 (3.0 mg/kg) | Clearance (CL) | Cycle 1 Day 15 | 15.15 liters per hour | Standard Deviation 2.65 |
| SL-172154 (10.0 mg/kg) | Clearance (CL) | Cycle 1 Day 15 | 4.44 liters per hour | — |
| SL-172154 (10.0 mg/kg) | Clearance (CL) | Cycle 1 Day 1 | 4.13 liters per hour | Standard Deviation 2.605 |
| SL-172154 (10.0 mg/kg) | Clearance (CL) | Cycle 2 Day 1 | 3.17 liters per hour | Standard Deviation 1.637 |
Secondary
Immunogenicity to SL-172154
Number of participants with positive anti-drug antibody (ADA) titer, sustained ADA response (positive ADA in \>/= 2 samples without reverting to negative ADA or positive ADA in the last sample), or persistent ADA response (positive ADA in \>/= 2 samples where the first and last samples are \>/= 16 weeks apart, or positive ADA in the last sample, or only one sample but \< 16 weeks before a negative last sample).
Time frame: Approximately 24 months
Population: Immunogenicity Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SL-172154 (0.1 mg/kg) | Immunogenicity to SL-172154 | Positive anti-drug antibody titer | 1 Participants |
| SL-172154 (0.1 mg/kg) | Immunogenicity to SL-172154 | Persistent ADA response | 0 Participants |
| SL-172154 (0.1 mg/kg) | Immunogenicity to SL-172154 | Sustained ADA response | 1 Participants |
| SL-172154 (0.3 mg/kg) | Immunogenicity to SL-172154 | Sustained ADA response | 3 Participants |
| SL-172154 (0.3 mg/kg) | Immunogenicity to SL-172154 | Positive anti-drug antibody titer | 4 Participants |
| SL-172154 (0.3 mg/kg) | Immunogenicity to SL-172154 | Persistent ADA response | 1 Participants |
| SL-172154 (1.0 mg/kg) | Immunogenicity to SL-172154 | Sustained ADA response | 2 Participants |
| SL-172154 (1.0 mg/kg) | Immunogenicity to SL-172154 | Positive anti-drug antibody titer | 2 Participants |
| SL-172154 (1.0 mg/kg) | Immunogenicity to SL-172154 | Persistent ADA response | 1 Participants |
| SL-172154 (3.0 mg/kg) | Immunogenicity to SL-172154 | Positive anti-drug antibody titer | 3 Participants |
| SL-172154 (3.0 mg/kg) | Immunogenicity to SL-172154 | Persistent ADA response | 1 Participants |
| SL-172154 (3.0 mg/kg) | Immunogenicity to SL-172154 | Sustained ADA response | 1 Participants |
| SL-172154 (10.0 mg/kg) | Immunogenicity to SL-172154 | Sustained ADA response | 1 Participants |
| SL-172154 (10.0 mg/kg) | Immunogenicity to SL-172154 | Positive anti-drug antibody titer | 3 Participants |
| SL-172154 (10.0 mg/kg) | Immunogenicity to SL-172154 | Persistent ADA response | 0 Participants |
Secondary
Maximum Serum Concentration (Cmax) of SL-172154
The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SL-172154 (0.1 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 1 | 117.68 ng/mL | Geometric Coefficient of Variation 31.06 |
| SL-172154 (0.1 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 2 Day 1 | 72.96 ng/mL | Geometric Coefficient of Variation 55.09 |
| SL-172154 (0.1 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 15 | 59.20 ng/mL | Geometric Coefficient of Variation 29.92 |
| SL-172154 (0.3 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 15 | 136.96 ng/mL | Geometric Coefficient of Variation 93.93 |
| SL-172154 (0.3 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 1 | 126.33 ng/mL | Geometric Coefficient of Variation 89.2 |
| SL-172154 (0.3 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 2 Day 1 | 82.11 ng/mL | Geometric Coefficient of Variation 14.84 |
| SL-172154 (1.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 15 | 1772.77 ng/mL | Geometric Coefficient of Variation 111.1 |
| SL-172154 (1.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 1 | 545.03 ng/mL | Geometric Coefficient of Variation 406.44 |
| SL-172154 (1.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 2 Day 1 | 1240.25 ng/mL | Geometric Coefficient of Variation 72.61 |
| SL-172154 (3.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 1 | 4593.19 ng/mL | Geometric Coefficient of Variation 90.34 |
| SL-172154 (3.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 2 Day 1 | 5219.40 ng/mL | Geometric Coefficient of Variation 151.02 |
| SL-172154 (3.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 15 | 3071.26 ng/mL | Geometric Coefficient of Variation 883.11 |
| SL-172154 (10.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 15 | 50484.31 ng/mL | Geometric Coefficient of Variation 33.38 |
| SL-172154 (10.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 1 Day 1 | 87509.31 ng/mL | Geometric Coefficient of Variation 51.12 |
| SL-172154 (10.0 mg/kg) | Maximum Serum Concentration (Cmax) of SL-172154 | Cycle 2 Day 1 | 115536.25 ng/mL | Geometric Coefficient of Variation 51.83 |
Secondary
Minimum Serum Concentration (Cmin) of SL-172154
The Cmin is the minimum observed serum concentration of SL-172154 following at least one dose
Time frame: Cycle 1 Day 15 and Cycle 2 Day 1 (each cycle = 28 days)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| SL-172154 (0.1 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 1 Day 15 | 0 ng/mL |
| SL-172154 (0.1 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 2 Day 1 | 0 ng/mL |
| SL-172154 (0.3 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 1 Day 15 | 0 ng/mL |
| SL-172154 (0.3 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 2 Day 1 | 0 ng/mL |
| SL-172154 (1.0 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 1 Day 15 | 0 ng/mL |
| SL-172154 (1.0 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 2 Day 1 | 0 ng/mL |
| SL-172154 (3.0 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 2 Day 1 | 0 ng/mL |
| SL-172154 (3.0 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 1 Day 15 | 0 ng/mL |
| SL-172154 (10.0 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 1 Day 15 | 0 ng/mL |
| SL-172154 (10.0 mg/kg) | Minimum Serum Concentration (Cmin) of SL-172154 | Cycle 2 Day 1 | 0 ng/mL |
Secondary
Recommended Phase 2 Dose (RP2D) for SL-172154
Based on review of all data, including safety, tolerability, PK, antitumor activity, and PD effects
Time frame: Approximately 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SL-172154 (0.1 mg/kg) | Recommended Phase 2 Dose (RP2D) for SL-172154 | 3.0 mg/kg |
Secondary
Terminal Elimination Half-life (t1/2)
Terminal elimination half-life (t1/2) of SL-172154
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SL-172154 (0.1 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 1 | NA hours | — |
| SL-172154 (0.1 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 2 Day 1 | NA hours | — |
| SL-172154 (0.1 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 15 | NA hours | — |
| SL-172154 (0.3 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 15 | NA hours | — |
| SL-172154 (0.3 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 1 | 0.50 hours | — |
| SL-172154 (0.3 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 2 Day 1 | NA hours | — |
| SL-172154 (1.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 15 | NA hours | — |
| SL-172154 (1.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 1 | 0.37 hours | Standard Deviation 0.056 |
| SL-172154 (1.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 2 Day 1 | NA hours | — |
| SL-172154 (3.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 1 | 0.75 hours | Standard Deviation 0.71 |
| SL-172154 (3.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 2 Day 1 | 0.36 hours | Standard Deviation 0.158 |
| SL-172154 (3.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 15 | 0.32 hours | Standard Deviation 0.132 |
| SL-172154 (10.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 15 | 0.71 hours | — |
| SL-172154 (10.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 1 Day 1 | 0.86 hours | Standard Deviation 0.278 |
| SL-172154 (10.0 mg/kg) | Terminal Elimination Half-life (t1/2) | Cycle 2 Day 1 | 1.30 hours | Standard Deviation 0.477 |
Secondary
Time at Which Maximum Concentration of SL-172154 is Observed (Tmax)
The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Population: PK Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SL-172154 (0.1 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 1 | 0.5 hours |
| SL-172154 (0.1 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 2 Day 1 | 0.5 hours |
| SL-172154 (0.1 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 15 | 0.53 hours |
| SL-172154 (0.3 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 15 | 0.54 hours |
| SL-172154 (0.3 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 1 | 0.56 hours |
| SL-172154 (0.3 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 2 Day 1 | 0.53 hours |
| SL-172154 (1.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 15 | 0.57 hours |
| SL-172154 (1.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 1 | 0.55 hours |
| SL-172154 (1.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 2 Day 1 | 0.55 hours |
| SL-172154 (3.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 1 | 2.53 hours |
| SL-172154 (3.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 2 Day 1 | 2.08 hours |
| SL-172154 (3.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 15 | 2.06 hours |
| SL-172154 (10.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 15 | 3.6 hours |
| SL-172154 (10.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 1 Day 1 | 3.43 hours |
| SL-172154 (10.0 mg/kg) | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | Cycle 2 Day 1 | 1.97 hours |
Secondary
Volume of Distribution
Volume of distribution of SL-172154
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (each cycle = 28 days)
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SL-172154 (0.1 mg/kg) | Volume of Distribution | Cycle 1 Day 15 | NA liters | — |
| SL-172154 (0.1 mg/kg) | Volume of Distribution | Cycle 1 Day 1 | NA liters | — |
| SL-172154 (0.1 mg/kg) | Volume of Distribution | Cycle 2 Day 1 | NA liters | — |
| SL-172154 (0.3 mg/kg) | Volume of Distribution | Cycle 1 Day 15 | NA liters | — |
| SL-172154 (0.3 mg/kg) | Volume of Distribution | Cycle 1 Day 1 | 79.83 liters | — |
| SL-172154 (0.3 mg/kg) | Volume of Distribution | Cycle 2 Day 1 | NA liters | — |
| SL-172154 (1.0 mg/kg) | Volume of Distribution | Cycle 1 Day 15 | NA liters | — |
| SL-172154 (1.0 mg/kg) | Volume of Distribution | Cycle 1 Day 1 | 64.28 liters | Standard Deviation 28.528 |
| SL-172154 (1.0 mg/kg) | Volume of Distribution | Cycle 2 Day 1 | NA liters | — |
| SL-172154 (3.0 mg/kg) | Volume of Distribution | Cycle 1 Day 1 | 28.46 liters | Standard Deviation 17.148 |
| SL-172154 (3.0 mg/kg) | Volume of Distribution | Cycle 2 Day 1 | 32.01 liters | Standard Deviation 49.282 |
| SL-172154 (3.0 mg/kg) | Volume of Distribution | Cycle 1 Day 15 | 7.32 liters | Standard Deviation 4.187 |
| SL-172154 (10.0 mg/kg) | Volume of Distribution | Cycle 1 Day 15 | 4.53 liters | — |
| SL-172154 (10.0 mg/kg) | Volume of Distribution | Cycle 1 Day 1 | 4.84 liters | Standard Deviation 2.982 |
| SL-172154 (10.0 mg/kg) | Volume of Distribution | Cycle 2 Day 1 | 5.62 liters | Standard Deviation 3.337 |