Epithelial Ovarian Cancer, Fallopian Tube Cancer, Ovarian Cancer, Platinum-Resistant Fallopian Tube Carcinoma, Platinum-resistant Ovarian Cancer, Platinum-Resistant Primary Peritoneal Carcinoma, Primary Peritoneal Carcinoma
Conditions
Keywords
Platinum-resistant, Ovarian, Peritoneal, High grade serous EOC, primary peritoneal cancer, Fallopian, Combination, Mirvetuximab Soravtansine, SL-172154, SIRPα-Fc-CD40L, Pegylated Liposomal Doxorubicin
Brief summary
SL03-OHD-105 is an open-label, multicenter, phase 1b trial designed to evaluate SL-172154 administered in combination with pegylated liposomal doxorubicin (PLD) or mirvetuximab soravtansine (MIRV) in patients with platinum resistant ovarian cancer. Approximately 102 patients will be enrolled in this study.
Detailed description
Study SL03-OHD-105 is an open-label, multicenter, phase 1b trial designed to evaluate the safety, pharmacokinetics, pharmacodynamic effects, and preliminary anti-tumor activity of SL-172154 administered in combination with either PLD or MIRV in subjects with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers. Patients will be appropriate for combination therapy for their next line of therapy. For the SL-172154 + MIRV cohort, patients' tumors must be positive (defined as PS2+ ≥ 25%) for folate receptor alpha (FRα) as defined by the Ventana FOLR1 (Folate Receptor 1/Folate Receptor Alpha) Assay. The first portion of the study will evaluate the safety of increasing dose levels of SL-172154 in combination with either PLD or MIRV and establish a combination dose for both regimens to be further evaluated in two dose expansion cohorts.
Interventions
DRUGPegylated Liposomal Doxorubicin + SL-172154
The investigational product, SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.
DRUGMirvetuximab + SL-172154
The investigational product, 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
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject has voluntarily agreed to participate by giving written informed consent in accordance with ICH/GCP guidelines and applicable local regulations. 2. Age ≥18 years 3. \[PLD Cohort\] Subject has a histologically confirmed diagnosis of high grade epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube cancer. Non-epithelial tumors and ovarian tumors with low malignant potential are excluded. 4. \[PLD Cohort\] Subject must have platinum-resistant disease, defined as radiologic disease progression within 180 days (6 months) following the last administered dose of platinum therapy. Subjects who are primary platinum-refractory, defined by progressing during or within 1 month of upfront platinum therapy, are excluded. 5. \[PLD Cohort\] Subjects may have received any number of prior lines of therapy for epithelial ovarian cancer; however, they may not have received more than 1 prior line of systemic anticancer therapy for platinum-resistant disease. 6. \[MIRV Cohort\] Subject has a histologically confirmed diagnosis of high grade serous epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube cancer. Non-epithelial tumors and ovarian tumors with low malignant potential are excluded. 7. \[MIRV Cohort\] Subject must have platinum-resistant disease as defined by: * Subjects who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (complete response/remission \[CR\] or partial response/remission \[PR\]) and then progressed between \>3 months and ≤6 months after the date of the last dose of platinum. * Subjects who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum. * Subjects who are platinum refractory during front-line treatment are excluded \[primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first-line platinum-containing chemotherapy\] 8. \[MIRV Cohort\] Subjects must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy. 9. \[MIRV Cohort\] Willing to provide an archival tumor tissue block or slides or undergo procedure to obtain new biopsy using a low-risk, medically routine procedure for IHC confirmation of FRα positivity. 10. \[MIRV Cohort\] Subject's tumor must be positive for FRα expression (defined as PS2+ ≥ 25% by the Ventana FOLR1 Assay). 11. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. 12. Measurable disease by RECIST v1.1 using radiologic assessment. 13. Adequate organ and hematologic function 14. Subjects must have stabilized or recovered (Grade 1 or baseline) from all prior anti-cancer therapy-related toxicities. 15. \[MIRV Cohort, Dose Expansion only\] Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy, unless there is excessive risk from the procedure as determined by the investigator
Exclusion criteria
1. Prior treatment with a signal-regulatory protein alpha (SIRPα) targeting agent, anti-CD47 agent or CD40 agonist. 2. \[PLD Cohort\] Prior treatment with doxorubicin or PLD 3. \[MIRV Cohort\] Prior treatment with MIRV or another FRα-targeting agent 4. Any anti-cancer therapy within the time intervals specified per protocol. 5. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment is prohibited. 6. Receipt of live attenuated vaccine (including live attenuated vaccines for COVID-19) within 28 days of the first dose of study treatment. 7. Current or prior use of systemic immunosuppressive medication within 7 days prior to first dose of study treatment. 8. \[MIRV Cohort\] Requires use of folate-containing supplements (e.g., folate deficiency) 9. Active or documented history of autoimmune disease that has required treatment with a disease modifying agent or immunosuppressive therapy in the past two years, history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome). Exceptions include controlled Type I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism. 10. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 5 days of D1 of study treatment). 11. Known severe hypersensitivity to the active drug substance or to any of the excipients for the agents to be administered or known hypersensitivity to Chinese hamster ovary cell products. 12. Severe gastrointestinal conditions. 13. Clinically significant or uncontrolled cardiovascular disease 14. \[MIRV Cohort\] History of cirrhotic liver disease (Child-Pugh Class B or C) 15. \[MIRV Cohort\] Active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and/or monocular vision. 16. Previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonia. 17. Untreated central nervous system or leptomeningeal metastases. 18. 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 the study treatment. 19. Has undergone allogeneic stem cell transplantation or organ transplantation. 20. Known history or positive test for human immunodeficiency virus (HIV), or positive test for hepatitis B (positive for hepatitis B surface antigen \[HBsAg\]) or hepatitis C virus (\[HCV\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Safety and Tolerability of SL-172154 When Administered With PLD or Mirvetixumab | From Day 1 to 30 days after last dose of SL-172154, PLD or Mirvetixumab, an average of approximately 6 months | Number of participants with treatment emergent adverse events from dose escalation and expansion cohorts |
| Establish the Recommended Phase 2 Dose (RP2D) for SL-172154 When Administered With PLD or Mirvetixumab | From Day 1 to 30 days after last dose of SL-172154, PLD or Mirvetixumab, an average of approximately 6 months | Based on review of all data, including safety, tolerability, PK, antitumor activity, and PD effects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity to MIRV | approximately 24 months | Number and proportion of participants with positive anti-drug antibody titer of those who were ADA negative at baseline |
| Maximum Serum Concentration (Cmax) of SL-172154 | C1D8, C1D15, C2D8 | The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses |
| Area Under the Serum Concentration-time Curve (AUC) of SL-172154 | C1D8, C1D15 and C2D8 | The AUC is the area under the serum concentration time curve of SL-172154 following single and multiple doses |
| To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | approximately 24 months | Overall response rate per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) |
| Maximum Serum Concentration (Cmax) of MIRV | Day 1 of each cycle, pre-dose and end of infusion (EOI) | The Cmax is the maximum observed serum concentration of MIRV following single and multiple doses |
| Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | Day 1 of each cycle, pre-dose and end of infusion (EOI) | The Cmax is the maximum observed serum concentration of Total Antibody (MIRV) following single and multiple doses |
| Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | Day 1 of each cycle, pre-dose and end of infusion (EOI) | The Cmax is the maximum observed serum concentration of DM4 Payload and S-Methyl DM4 payload following single and multiple doses |
| Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | C1D8, C1D15 and C2D8 | The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses |
| Immunogenicity to SL-172154 | approximately 24 months | Number and proportion of participants with positive anti-drug antibody titer of those who were ADA negative at baseline |
Countries
Canada, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Dose escalation was limited to a single dose level for SL-172154 within each arm (in combination with the standard dose of PLD or MIRV). No participants were enrolled in other dose levels in either arm.
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 3.0 mg/kg SL-172154 on Days 8 and15 of every 28-day cycle plus pegylated liposomal doxorubicin (PLD) 40 mg/m2 on Day 1 of every 28-day cycle | 21 |
| Mirvetuximab + SL-172154 3.0 mg/kg SL-172154 on Days 8 and 15 of every 21-day cycle plus mirvetuximab (MIRV) 6.0 mg/kg on Day 1 of every 21-day cycle | 65 |
| Total | 86 |
Baseline characteristics
| Characteristic | Pegylated Liposomal Doxorubicin + SL-172154 | Total | Mirvetuximab + SL-172154 |
|---|---|---|---|
| Age, Continuous | 58 years | 64 years | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 76 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 20 Participants | 78 Participants | 58 Participants |
| Region of Enrollment Canada | 3 Participants | 25 Participants | 22 Participants |
| Region of Enrollment Spain | 5 Participants | 29 Participants | 24 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 19 Participants | 13 Participants |
| Region of Enrollment United States | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Female | 21 Participants | 86 Participants | 65 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 21 | 30 / 65 |
| other Total, other adverse events | 20 / 21 | 65 / 65 |
| serious Total, serious adverse events | 4 / 21 | 17 / 65 |
Outcome results
Primary
Establish the Recommended Phase 2 Dose (RP2D) for SL-172154 When Administered With PLD or Mirvetixumab
Based on review of all data, including safety, tolerability, PK, antitumor activity, and PD effects
Time frame: From Day 1 to 30 days after last dose of SL-172154, PLD or Mirvetixumab, an average of approximately 6 months
Population: DLT evaluable population (Dose Escalation only)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Establish the Recommended Phase 2 Dose (RP2D) for SL-172154 When Administered With PLD or Mirvetixumab | 3.0 mg/kg |
| Mirvetixumab + SL-172154 | Establish the Recommended Phase 2 Dose (RP2D) for SL-172154 When Administered With PLD or Mirvetixumab | 3.0 mg/kg |
Primary
Evaluate Safety and Tolerability of SL-172154 When Administered With PLD or Mirvetixumab
Number of participants with treatment emergent adverse events from dose escalation and expansion cohorts
Time frame: From Day 1 to 30 days after last dose of SL-172154, PLD or Mirvetixumab, an average of approximately 6 months
Population: Subjects who received at least one dose of SL-172154, PLD or Mirvetixumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Evaluate Safety and Tolerability of SL-172154 When Administered With PLD or Mirvetixumab | 20 Participants |
| Mirvetixumab + SL-172154 | Evaluate Safety and Tolerability of SL-172154 When Administered With PLD or Mirvetixumab | 65 Participants |
Secondary
Area Under the Serum Concentration-time Curve (AUC) of SL-172154
The AUC is the area under the serum concentration time curve of SL-172154 following single and multiple doses
Time frame: C1D8, C1D15 and C2D8
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 |
|---|---|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Area Under the Serum Concentration-time Curve (AUC) of SL-172154 | C1D8 | 9798.72 h*ng/mL | Geometric Coefficient of Variation 239.36 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Area Under the Serum Concentration-time Curve (AUC) of SL-172154 | C1D15 | 20157.25 h*ng/mL | Geometric Coefficient of Variation 87.41 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Area Under the Serum Concentration-time Curve (AUC) of SL-172154 | C2D8 | 11619.44 h*ng/mL | Geometric Coefficient of Variation 132.43 |
| Mirvetixumab + SL-172154 | Area Under the Serum Concentration-time Curve (AUC) of SL-172154 | C1D8 | 27736.48 h*ng/mL | Geometric Coefficient of Variation 79.72 |
| Mirvetixumab + SL-172154 | Area Under the Serum Concentration-time Curve (AUC) of SL-172154 | C1D15 | 15324.37 h*ng/mL | Geometric Coefficient of Variation 82.77 |
| Mirvetixumab + SL-172154 | Area Under the Serum Concentration-time Curve (AUC) of SL-172154 | C2D8 | 21906.25 h*ng/mL | Geometric Coefficient of Variation 116.59 |
Secondary
Immunogenicity to MIRV
Number and proportion of participants with positive anti-drug antibody titer of those who were ADA negative at baseline
Time frame: approximately 24 months
Population: Immunogenicity population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Immunogenicity to MIRV | 8 Participants |
Secondary
Immunogenicity to SL-172154
Number and proportion of participants with positive anti-drug antibody titer of those who were ADA negative at baseline
Time frame: approximately 24 months
Population: Immunogenicity population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Immunogenicity to SL-172154 | 0 Participants |
| Mirvetixumab + SL-172154 | Immunogenicity to SL-172154 | 38 Participants |
Secondary
Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV)
The Cmax is the maximum observed serum concentration of DM4 Payload and S-Methyl DM4 payload following single and multiple doses
Time frame: Day 1 of each cycle, pre-dose and end of infusion (EOI)
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 |
|---|---|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C9D1-PREDOSE | NA ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C3D1-PREDOSE | NA ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C7D1-PREDOSE | NA ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C8D1-EOI | 2.591 ng/mL | Geometric Coefficient of Variation 29.962 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C1D1-EOI | 4.539 ng/mL | Geometric Coefficient of Variation 40.775 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C2D1-EOI | 4.353 ng/mL | Geometric Coefficient of Variation 48.036 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C3D1-EOI | 4.242 ng/mL | Geometric Coefficient of Variation 45.189 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C4D1-PREDOSE | 0.105 ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C4D1-EOI | 4.190 ng/mL | Geometric Coefficient of Variation 39.346 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C5D1-PREDOSE | 0.143 ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C5D1-EOI | 3.495 ng/mL | Geometric Coefficient of Variation 49.81 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C6D1-PREDOSE | NA ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C6D1-EOI | 3.370 ng/mL | Geometric Coefficient of Variation 38.46 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C7D1-EOI | 3.486 ng/mL | Geometric Coefficient of Variation 55.862 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C8D1-PREDOSE | NA ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C2D1-PREDOSE | 0.102 ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C9D1-EOI | 1.847 ng/mL | Geometric Coefficient of Variation 30.813 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C10D1-PREDOSE | NA ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C10D1-EOI | 2.583 ng/mL | Geometric Coefficient of Variation 74.475 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C11D1-PREDOSE | NA ng/mL | — |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C11D1-EOI | 2.245 ng/mL | Geometric Coefficient of Variation 9.463 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C5D1-EOI | 1.812 ng/mL | Geometric Coefficient of Variation 73.839 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C9D1-PREDOSE | 0.526 ng/mL | Geometric Coefficient of Variation 24.536 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C3D1-PREDOSE | 0.711 ng/mL | Geometric Coefficient of Variation 98.646 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C4D1-PREDOSE | 0.645 ng/mL | Geometric Coefficient of Variation 81.145 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C6D1-EOI | 1.963 ng/mL | Geometric Coefficient of Variation 53.07 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C6D1-PREDOSE | 0.565 ng/mL | Geometric Coefficient of Variation 34.199 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C11D1-PREDOSE | 0.728 ng/mL | Geometric Coefficient of Variation 77.13 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C11D1-EOI | 1.544 ng/mL | Geometric Coefficient of Variation 23.568 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C7D1-PREDOSE | 0.500 ng/mL | Geometric Coefficient of Variation 67.093 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C1D1-EOI | 0.191 ng/mL | Geometric Coefficient of Variation 52.463 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C2D1-PREDOSE | 0.798 ng/mL | Geometric Coefficient of Variation 108.344 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C9D1-EOI | 1.438 ng/mL | Geometric Coefficient of Variation 50.514 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C2D1-EOI | 3.228 ng/mL | Geometric Coefficient of Variation 86.763 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C7D1-EOI | 1.460 ng/mL | Geometric Coefficient of Variation 117.897 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C3D1-EOI | 2.712 ng/mL | Geometric Coefficient of Variation 82.341 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C10D1-EOI | 1.599 ng/mL | Geometric Coefficient of Variation 56.348 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C8D1-PREDOSE | 0.736 ng/mL | Geometric Coefficient of Variation 53.285 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C4D1-EOI | 2.336 ng/mL | Geometric Coefficient of Variation 61.288 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C8D1-EOI | 2.238 ng/mL | Geometric Coefficient of Variation 64.838 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C5D1-PREDOSE | 0.513 ng/mL | Geometric Coefficient of Variation 57.029 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of DM4 Payload and S-Methyl DM4 Payload (MIRV) | C10D1-PREDOSE | 0.700 ng/mL | Geometric Coefficient of Variation 17.815 |
Secondary
Maximum Serum Concentration (Cmax) of MIRV
The Cmax is the maximum observed serum concentration of MIRV following single and multiple doses
Time frame: Day 1 of each cycle, pre-dose and end of infusion (EOI)
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 |
|---|---|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C4D1-EOI | 125434.5 ng/mL | Geometric Coefficient of Variation 16.1 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C1D1 EOI | 137446.1 ng/mL | Geometric Coefficient of Variation 15.8 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C2D1 Predose | 3752.7 ng/mL | Geometric Coefficient of Variation 54.7 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C2D1- EOI | 121883.2 ng/mL | Geometric Coefficient of Variation 71.5 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C3D1-PREDOSE | 4210.7 ng/mL | Geometric Coefficient of Variation 49.9 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C3D1-EOI | 122156.1 ng/mL | Geometric Coefficient of Variation 61.7 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C4D1-PREDOSE | 3792.1 ng/mL | Geometric Coefficient of Variation 74.4 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C5D1-PREDOSE | 4296.6 ng/mL | Geometric Coefficient of Variation 55.4 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C5D1-EOI | 130739.7 ng/mL | Geometric Coefficient of Variation 14.3 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C6D1-PREDOSE | 4454.2 ng/mL | Geometric Coefficient of Variation 58.8 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C6D1-EOI | 117049.6 ng/mL | Geometric Coefficient of Variation 11.5 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C7D1-PREDOSE | 3896.1 ng/mL | Geometric Coefficient of Variation 64.2 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C7D1-EOI | 103871.8 ng/mL | Geometric Coefficient of Variation 16 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C8D1-PREDOSE | 5020.3 ng/mL | Geometric Coefficient of Variation 40.6 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C8D1-EOI | 108193.1 ng/mL | Geometric Coefficient of Variation 13.3 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C9D1-PREDOSE | 4989.8 ng/mL | Geometric Coefficient of Variation 50.1 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C9D1-EOI | 105523.9 ng/mL | Geometric Coefficient of Variation 16.4 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C10D1-PREDOSE | 3372.2 ng/mL | Geometric Coefficient of Variation 116.3 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C10D1-EOI | 105655.2 ng/mL | Geometric Coefficient of Variation 11.2 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C11D1-PREDOSE | 5094.8 ng/mL | Geometric Coefficient of Variation 19 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of MIRV | C11D1-EOI | 99787.8 ng/mL | Geometric Coefficient of Variation 11.2 |
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: C1D8, C1D15, C2D8
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 |
|---|---|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of SL-172154 | C1D8 | 6022.23 ng/mL | Geometric Coefficient of Variation 253.65 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of SL-172154 | C1D15 | 13893.69 ng/mL | Geometric Coefficient of Variation 90.44 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of SL-172154 | C2D8 | 7083.44 ng/mL | Geometric Coefficient of Variation 110.77 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of SL-172154 | C1D8 | 13248.42 ng/mL | Geometric Coefficient of Variation 96.7 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of SL-172154 | C1D15 | 8075.79 ng/mL | Geometric Coefficient of Variation 97.53 |
| Mirvetixumab + SL-172154 | Maximum Serum Concentration (Cmax) of SL-172154 | C2D8 | 10375.13 ng/mL | Geometric Coefficient of Variation 117.92 |
Secondary
Maximum Serum Concentration (Cmax) of Total Antibody (MIRV)
The Cmax is the maximum observed serum concentration of Total Antibody (MIRV) following single and multiple doses
Time frame: Day 1 of each cycle, pre-dose and end of infusion (EOI)
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 |
|---|---|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C8D1-PREDOSE | 24546.8 ng/mL | Geometric Coefficient of Variation 52.2 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C8D1-EOI | 121205.9 ng/mL | Geometric Coefficient of Variation 16.1 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C1D1-EOI | 135716.4 ng/mL | Geometric Coefficient of Variation 16 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C2D1-PREDOSE | 11901.6 ng/mL | Geometric Coefficient of Variation 65.7 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C2D1-EOI | 135856.9 ng/mL | Geometric Coefficient of Variation 49 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C3D1-PREDOSE | 15986.7 ng/mL | Geometric Coefficient of Variation 70.5 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C3D1-EOI | 137898.7 ng/mL | Geometric Coefficient of Variation 37.9 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C4D1-PREDOSE | 18388.2 ng/mL | Geometric Coefficient of Variation 61.7 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C4D1-EOI | 136454.6 ng/mL | Geometric Coefficient of Variation 18.7 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C5D1-PREDOSE | 20115.1 ng/mL | Geometric Coefficient of Variation 57.5 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C5D1-EOI | 138756.5 ng/mL | Geometric Coefficient of Variation 22.2 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C6D1-PREDOSE | 20283.3 ng/mL | Geometric Coefficient of Variation 63.6 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C6D1-EOI | 123020.4 ng/mL | Geometric Coefficient of Variation 28.7 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C7D1-PREDOSE | 19007.7 ng/mL | Geometric Coefficient of Variation 51.4 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C7D1-EOI | 115087.0 ng/mL | Geometric Coefficient of Variation 29 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C9D1-PREDOSE | 23604.6 ng/mL | Geometric Coefficient of Variation 69.5 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C9D1-EOI | 118301.1 ng/mL | Geometric Coefficient of Variation 12.6 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C10D1-PREDOSE | 17972.6 ng/mL | Geometric Coefficient of Variation 144.5 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C10D1-EOI | 110207.7 ng/mL | Geometric Coefficient of Variation 21.1 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C11D1-PREDOSE | 29331.9 ng/mL | Geometric Coefficient of Variation 9.7 |
| Pegylated Liposomal Doxorubicin + SL-172154 | Maximum Serum Concentration (Cmax) of Total Antibody (MIRV) | C11D1-EOI | 101638.6 ng/mL | Geometric Coefficient of Variation 57.1 |
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: C1D8, C1D15 and C2D8
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) |
|---|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | C1D8 | 2.07 hours |
| Pegylated Liposomal Doxorubicin + SL-172154 | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | C1D15 | 2.15 hours |
| Pegylated Liposomal Doxorubicin + SL-172154 | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | C2D8 | 2.05 hours |
| Mirvetixumab + SL-172154 | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | C1D8 | 2.22 hours |
| Mirvetixumab + SL-172154 | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | C1D15 | 2.03 hours |
| Mirvetixumab + SL-172154 | Time at Which Maximum Concentration of SL-172154 is Observed (Tmax) | C2D8 | 2.28 hours |
Secondary
To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab
Overall response rate per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
Time frame: approximately 24 months
Population: Response Evaluable Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pegylated Liposomal Doxorubicin + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Complete response | 0 Participants |
| Pegylated Liposomal Doxorubicin + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Progressive Disease | 6 Participants |
| Pegylated Liposomal Doxorubicin + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Stable Disease | 10 Participants |
| Pegylated Liposomal Doxorubicin + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Not Evaluable | 0 Participants |
| Pegylated Liposomal Doxorubicin + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Partial response | 4 Participants |
| Mirvetixumab + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Complete response | 1 Participants |
| Mirvetixumab + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Stable Disease | 21 Participants |
| Mirvetixumab + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Partial response | 12 Participants |
| Mirvetixumab + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Progressive Disease | 5 Participants |
| Mirvetixumab + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Not Evaluable | 0 Participants |
| Mirvetixumab Low+Medium ((PS2+ ≥25% to <75%) + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Not Evaluable | 0 Participants |
| Mirvetixumab Low+Medium ((PS2+ ≥25% to <75%) + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Progressive Disease | 9 Participants |
| Mirvetixumab Low+Medium ((PS2+ ≥25% to <75%) + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Complete response | 0 Participants |
| Mirvetixumab Low+Medium ((PS2+ ≥25% to <75%) + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Stable Disease | 13 Participants |
| Mirvetixumab Low+Medium ((PS2+ ≥25% to <75%) + SL-172154 | To Assess Preliminary Evidence of Anti-tumor Activity of SL-172154 When Administered With PLD or Mirvetixumab | Partial response | 4 Participants |