Hepatocellular Carcinoma
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of the investigational anticancer drug DCR-MYC. DCR-MYC is a novel synthetic double-stranded RNA in a stable lipid particle suspension that targets the oncogene MYC. MYC oncogene activation is important to the growth of many hematologic and solid tumor malignancies. In this study the Sponsor proposes to study DCR-MYC and its ability to inhibit MYC and thereby inhibit cancer cell growth.
Detailed description
In this second study in humans, DCR-MYC will be administered by 2 hour intravenous (IV) infusion, once weekly for 2 weeks followed by a rest week (3 weeks = 1 cycle), to patients with hepatocellular carcinoma who are either sorafenib-refractory, sorafenib-intolerant despite dose reduction and best supportive care, or for whom neither sorafenib nor other suitable therapy is available. During the Phase 1b portion of the study, the highest safe dose of DCR-MYC that can be administered will be identified. In addition, the pharmacokinetic (PK) profile, potential pharmacodynamic (PD) effects, as well as the preliminary antitumor activity of DCR-MYC will be evaluated. During the Phase 2 portion of the study, up to 30 patients will be treated at the MTD identified in Phase 1b in order to further evaluate safety and tolerability, as well as assess the antitumor activity, of DCR-MYC.
Interventions
DRUGDCR-MYC
Dosing: 2 hour IV infusion on Day 1 and 8 of each 21 day cycle. Starting dose: 0.125mg/kg/dose Number of cycles: until progression or unacceptable toxicity develops. PHASE 1b Dose escalation: 50% or 25% increase in subsequent cohorts depending upon toxicity until maximum tolerated dose (MTD) is identified. PHASE 2 Cohort expansion at the MTD: Additional patients to be treated at the highest dose tolerated to assess efficacy and further assess safety
Sponsors
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients, \> 18 years of age (in Singapore \> 21 years or \> 18 years with consent of guardian). 2. Patients with documented (histologically- or cytologically-proven) HCC, with at least 1 measureable lesion \> 10 mm (excluding bone metastases). If the measurable lesion(s) is in the liver, it either should not have been treated previously with loco-regional therapy, or there must be demonstrated progression of the lesion following previous loco-regional therapy. 3. Patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor. 4. Patients who are either refractory to or intolerant of sorafenib despite dose reduction and best supportive care, or patients who do not have access to sorafenib or other suitable therapy for HCC. 5. Patients with underlying hepatic cirrhosis must have a current cirrhosis status of Child-Pugh Class A (i.e., score of 5-6) without encephalopathy. 6. Phase 1b MTD Biopsy Cohort: Patients with primary or metastatic tumor site(s) considered safely accessible for biopsy and consenting to undergo pre- and post-dosing tumor biopsies. 7. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and an anticipated life expectancy of ≥ 3 months. 8. Patients, both male and female, who are either not of childbearing potential or who agree to use a medically effective method of contraception during the study and for 3 months after the last dose of study drug. 9. Patients with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol.
Exclusion criteria
(Patients): 1. Women who are pregnant or lactating; women of child-bearing potential (WOCBP), and fertile men with a WOCBP-partner not using and not willing to use a medically effective method of contraception. 2. Patients with known central nervous system (CNS) or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required. 3. Patients with mixed histology cholangiocarcinoma and HCC, or fibrolamellar variant HCC. 4. Patients with any of the following hematologic abnormalities at baseline: * Hemoglobin \< 8.5 g/dL * Absolute neutrophil count \< 1,500 per mm3 * Platelet count \< 75,000 per mm 5. Patients with any of the following serum chemistry abnormalities at baseline: * Total bilirubin \> 1.5 × the upper limit of normal (ULN) for the institution * AST or ALT \> 5 × the ULN for the institution * Serum creatinine \> 1.5 × the ULN for the institution 6. Patients with the following coagulation parameter abnormality at baseline: * INR \> 1.7 × ULN for the institution 7. Patients with: * A history of deep vein thrombosis (DVT) or pulmonary embolism (PE), within 6 months prior to first study drug administration; patients receiving systemic anti-coagulation for prophylactic or therapeutic reasons * Active uncontrolled bleeding or a known bleeding diathesis 8. Patients with: * Esophageal or gastric variceal bleeding within 2 months prior to first study drug administration; patients with a history of variceal bleeding between 2 and 12 months prior to first study drug administration should have undergone adequate treatment and be considered clinically stable in the opinion of the investigator * A history of symptomatic ascites requiring paracentesis within the past 3 months or any encephalopathy requiring hospitalization or medication within the past 3 months * Portal-caval shunts 9. Patients with a significant cardiovascular disease or condition, including: * Congestive heart failure currently requiring therapy * Need for antiarrhythmic medical therapy for a ventricular arrhythmia * Severe conduction disturbance (i.e., 3rd degree heart block) * Angina pectoris requiring therapy * Known left ventricular ejection fraction (LVEF) \< 50% by MUGA or echocardiogram * QTc interval \> 450 msec in males, or \> 470 msec in females * Uncontrolled systemic hypertension (per the Investigator's discretion) * Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) Functional Criteria * Myocardial infarction within 6 months prior to first study drug administration 10. Patients with a known or suspected hypersensitivity to any of the components of lipid nanoparticle-formulated DCR-MYC; patients with a known sensitivity to cremophor (found with paclitaxel and other formulations). 11. Patients with an estimated daily alcohol intake greater than 80 g/day. 12. Patients having undergone previous organ transplantation (e.g., liver transplantation) requiring immunosuppression; patients on long-term immunosuppressive therapy. 13. Patients with a known history of human immunodeficiency virus (HIV) seropositivity. 14. Patients with any other serious/active/uncontrolled infection, with the exception of chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection; any infection requiring parenteral antibiotics, or unexplained fever \> 38ºC within 2 weeks prior to first study drug administration. 15. Patients with inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy. 16. Patients with inadequate recovery from any previous surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to first study drug administration. 17. Patients with an active second malignancy or history of another malignancy within the last 3 years, with the exception of: * Treated, non-melanoma skin cancers * Treated CIS of the breast or cervix * Controlled, superficial carcinoma of the bladder * T1a or b carcinoma of the prostate treated according to local standard of care, with prostate specific antigen (PSA) within normal limits (wnl) 18. Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug. 19. Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study-related evaluations. 20. Patients with the inability or with foreseeable incapacity, in the opinion of the Investigator, to comply with the protocol requirements, including the ability to attend all visits and undergo all assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability | Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dose | Part A: 3 patient cohorts with 50% dose increase between cohorts until study drug-related dose-limiting toxicity (DLT) during Cycle 1, then expand to 6 patients and move to Part B. Part B: 3 to 6 patient cohorts with 25% dose increase between cohorts until \> 1 study drug-related DLT, then stop escalation. Expand MTD cohort to 12 patients; tumor biopsies to be performed in this Phase 1b MTD Biopsy Cohort (6 patients). |
| Phase 2: Patients With Adverse Events as a Measure of Safety and Tolerability | Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dose | Up to 30 patients in the Phase 2 MTD Expansion Cohort (to be treated at the MTD identified in Phase 1b); further evaluation of safety and tolerability. |
| Phase 2: Preliminary Antitumor Activity | After Cycle 2 (6 weeks), then at 6 week intervals if DCR-MYC is continued | Up to 30 patients in the Phase 2 MTD Expansion Cohort (to be treated at the MTD identified in Phase 1b); evaluation for evidence of objective response or disease stabilization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4 | Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8). |
| Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4 | Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8). |
| AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4 | Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8). |
| AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4 | Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8). |
| DCR-MYC Biological Activities (Phase 1b Only) | Cycle 1; Week 1 | Collection of blood samples for cytokine measurements (Day 1, 2, and 4). No noteworthy increases were observed across dose groups or time for GM-CSF, IFNα, IFNɣ, or IL-1β. Changes that were observed for the other cytokines were not dose-dependent since they occurred sporadically and primarily in Cohorts 3 (0.3 mg/kg) and 4 (0.45 mg/kg). Pre-dose, 4 hours post-dose, and 24 hour post-dose results for TNF-α, IL-10, IL-6, IL-8, IL-1RA, and MCP-1 are summarized here. |
| Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4 | Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8). |
Countries
Singapore, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DCR-MYC Patient groups (cohorts) will receive a single dose level of DCR-MYC; the dose level of DCR-MYC will be increased in subsequent cohorts
DCR-MYC: Dosing: 2 hour IV infusion on Day 1 and 8 of each 21 day cycle.
Starting dose: 0.125mg/kg/dose
Number of cycles: until progression or unacceptable toxicity develops.
PHASE 1b Dose escalation: 50% or 25% increase in subsequent cohorts depending upon toxicity until maximum tolerated dose (MTD) is identified.
PHASE 2 Cohort expansion at the MTD: Additional patients to be treated at the highest dose tolerated to assess efficacy and further assess safety | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Cycle One | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | DCR-MYC |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 64.1 years STANDARD_DEVIATION 7.24 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment Singapore | 7 Participants |
| Region of Enrollment South Korea | 8 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 19 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 0 / 3 | 3 / 3 | 1 / 3 | 3 / 6 | 2 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 0 / 3 | 1 / 3 | 2 / 6 | 1 / 3 |
Outcome results
Primary
Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Part A: 3 patient cohorts with 50% dose increase between cohorts until study drug-related dose-limiting toxicity (DLT) during Cycle 1, then expand to 6 patients and move to Part B. Part B: 3 to 6 patient cohorts with 25% dose increase between cohorts until \> 1 study drug-related DLT, then stop escalation. Expand MTD cohort to 12 patients; tumor biopsies to be performed in this Phase 1b MTD Biopsy Cohort (6 patients).
Time frame: Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dose
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability | 3 Participants |
| Cohort 2 | Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability | 3 Participants |
| Cohort 3 | Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability | 3 Participants |
| Cohort 4 | Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability | 3 Participants |
| Cohort 5 | Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability | 6 Participants |
| Cohort 6 | Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability | 3 Participants |
Primary
Phase 2: Patients With Adverse Events as a Measure of Safety and Tolerability
Up to 30 patients in the Phase 2 MTD Expansion Cohort (to be treated at the MTD identified in Phase 1b); further evaluation of safety and tolerability.
Time frame: Cycle 1 (3 weeks), longer if DCR-MYC is continued; with 30 days follow-up after last dose
Population: N/A - Study terminated prior to Phase 2
Primary
Phase 2: Preliminary Antitumor Activity
Up to 30 patients in the Phase 2 MTD Expansion Cohort (to be treated at the MTD identified in Phase 1b); evaluation for evidence of objective response or disease stabilization.
Time frame: After Cycle 2 (6 weeks), then at 6 week intervals if DCR-MYC is continued
Population: N/A - Study terminated prior to phase 2
Secondary
AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Time frame: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 1 | 178997 hr*kg*ng/mL/mg | Standard Deviation 125460 |
| Cohort 1 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 8 | 163478 hr*kg*ng/mL/mg | Standard Deviation 109924 |
| Cohort 2 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 1 | 299295 hr*kg*ng/mL/mg | Standard Deviation 312426 |
| Cohort 2 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 8 | 739203 hr*kg*ng/mL/mg | Standard Deviation 698459 |
| Cohort 3 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 1 | 197244 hr*kg*ng/mL/mg | Standard Deviation 116908 |
| Cohort 3 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 8 | 389653 hr*kg*ng/mL/mg | Standard Deviation 293467 |
| Cohort 4 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 1 | 195133 hr*kg*ng/mL/mg | Standard Deviation 56544 |
| Cohort 4 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 8 | 350625 hr*kg*ng/mL/mg | Standard Deviation 132910 |
| Cohort 5 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 1 | 290201 hr*kg*ng/mL/mg | Standard Deviation 169069 |
| Cohort 5 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 8 | 274941 hr*kg*ng/mL/mg | Standard Deviation 168548 |
| Cohort 6 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 1 | 201529 hr*kg*ng/mL/mg | Standard Deviation 45290 |
| Cohort 6 | AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast_D: Day 8 | 383537 hr*kg*ng/mL/mg | Standard Deviation 84286 |
Secondary
AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Time frame: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 1 | 22375 hr*ng/mL | Standard Deviation 15683 |
| Cohort 1 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 8 | 20435 hr*ng/mL | Standard Deviation 13741 |
| Cohort 2 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 1 | 59859 hr*ng/mL | Standard Deviation 62485 |
| Cohort 2 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 8 | 147841 hr*ng/mL | Standard Deviation 139692 |
| Cohort 3 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 1 | 59173 hr*ng/mL | Standard Deviation 35072 |
| Cohort 3 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 8 | 116896 hr*ng/mL | Standard Deviation 88040 |
| Cohort 4 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 1 | 87810 hr*ng/mL | Standard Deviation 25445 |
| Cohort 4 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 8 | 157781 hr*ng/mL | Standard Deviation 59810 |
| Cohort 5 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 1 | 197337 hr*ng/mL | Standard Deviation 114967 |
| Cohort 5 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 8 | 186960 hr*ng/mL | Standard Deviation 114612 |
| Cohort 6 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 1 | 171299 hr*ng/mL | Standard Deviation 38496 |
| Cohort 6 | AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | AUClast : Day 8 | 326006 hr*ng/mL | Standard Deviation 71643 |
Secondary
Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Time frame: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 1 | 16832 kg*ng/mL/mg | Standard Deviation 10192 |
| Cohort 1 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 8 | 14045 kg*ng/mL/mg | Standard Deviation 475.74 |
| Cohort 2 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 1 | 23952 kg*ng/mL/mg | Standard Deviation 17701 |
| Cohort 2 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 8 | 27525 kg*ng/mL/mg | Standard Deviation 16827 |
| Cohort 3 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 1 | 20652 kg*ng/mL/mg | Standard Deviation 2482.5 |
| Cohort 3 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 8 | 22095 kg*ng/mL/mg | Standard Deviation 3852.7 |
| Cohort 4 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 1 | 21794 kg*ng/mL/mg | Standard Deviation 9098.8 |
| Cohort 4 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 8 | 29964 kg*ng/mL/mg | Standard Deviation 5724.8 |
| Cohort 5 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 1 | 28527 kg*ng/mL/mg | Standard Deviation 12076 |
| Cohort 5 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 8 | 30457 kg*ng/mL/mg | Standard Deviation 20247 |
| Cohort 6 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 1 | 23384 kg*ng/mL/mg | Standard Deviation 4241.4 |
| Cohort 6 | Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax_D: Day 8 | 31931 kg*ng/mL/mg | Standard Deviation 10677 |
Secondary
Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Time frame: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 1 | 2094.3 ng/mL | Standard Deviation 1257.8 |
| Cohort 1 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 8 | 1755.7 ng/mL | Standard Deviation 59.47 |
| Cohort 2 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 1 | 4790.5 ng/mL | Standard Deviation 3540.2 |
| Cohort 2 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 8 | 5504.9 ng/mL | Standard Deviation 3365.3 |
| Cohort 3 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 1 | 6195.7 ng/mL | Standard Deviation 744.75 |
| Cohort 3 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 8 | 6628.4 ng/mL | Standard Deviation 1155.8 |
| Cohort 4 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 1 | 9807.1 ng/mL | Standard Deviation 4094.5 |
| Cohort 4 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 8 | 13484 ng/mL | Standard Deviation 2576.2 |
| Cohort 5 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 1 | 19399 ng/mL | Standard Deviation 8211.4 |
| Cohort 5 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 8 | 20711 ng/mL | Standard Deviation 13768 |
| Cohort 6 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 1 | 19829 ng/mL | Standard Deviation 3686.2 |
| Cohort 6 | Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Cmax: Day 8 | 27067 ng/mL | Standard Deviation 9105.1 |
Secondary
DCR-MYC Biological Activities (Phase 1b Only)
Tumor biopsies (2 total) to be performed in Phase 1b MTD expansion cohort only (6 patients). Patients will have biopsies performed prior to Cycle 1/Day 1 and on Cycle 2/Day 11.
Time frame: Cycle 1 and 2
Population: Planned expansion into the MTD biopsy cohort and phase 2 portion of the study did not occur due to the sponsor's decision to prematurely end the study.
Secondary
DCR-MYC Biological Activities (Phase 1b Only)
Collection of blood samples for cytokine measurements (Day 1, 2, and 4). No noteworthy increases were observed across dose groups or time for GM-CSF, IFNα, IFNɣ, or IL-1β. Changes that were observed for the other cytokines were not dose-dependent since they occurred sporadically and primarily in Cohorts 3 (0.3 mg/kg) and 4 (0.45 mg/kg). Pre-dose, 4 hours post-dose, and 24 hour post-dose results for TNF-α, IL-10, IL-6, IL-8, IL-1RA, and MCP-1 are summarized here.
Time frame: Cycle 1; Week 1
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA pre-dose | 10.2 pg/mL | Standard Deviation 7.7 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 pre-dose | 317.5 pg/mL | Standard Deviation 60.9 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 pre-dose | 8.7 pg/mL | Standard Deviation 2.7 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α Pre-dose | 2.3 pg/mL | Standard Deviation 1.3 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 4 hour post | 241.1 pg/mL | Standard Deviation 61.3 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 24 hour post-dose | 162.1 pg/mL | Standard Deviation 69.8 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 4 hour post-dose | 4.1 pg/mL | Standard Deviation 4.3 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 pre-dose | 101.2 pg/mL | Standard Deviation 13.1 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 24 hour post-dose | 2.2 pg/mL | Standard Deviation 1 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 4 hour post-dose | 90.0 pg/mL | Standard Deviation 18.8 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 24 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 4 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 24 hour post-dose | 5.3 pg/mL | Standard Deviation 6.4 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 24 hour post-dose | 9.0 pg/mL | Standard Deviation 2.8 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 4 hour post-dose | 8.2 pg/mL | Standard Deviation 3.1 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 4 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 1 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 24 hour post | 322.5 pg/mL | Standard Deviation 152.9 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 24 hour post-dose | 119.5 pg/mL | Standard Deviation 69 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA pre-dose | 26.4 pg/mL | Standard Deviation 26.3 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 4 hour post-dose | 3.3 pg/mL | Standard Deviation 2.9 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 24 hour post-dose | 13.3 pg/mL | Standard Deviation 10.2 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 24 hour post-dose | 4.1 pg/mL | Standard Deviation 0.5 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 pre-dose | 239.4 pg/mL | Standard Deviation 83.7 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 4 hour post | 159.6 pg/mL | Standard Deviation 104.2 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 24 hour post | 424.4 pg/mL | Standard Deviation 296.4 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 4 hour post-dose | 46.0 pg/mL | Standard Deviation 23.6 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 4 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 4 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 24 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 pre-dose | 2.2 pg/mL | Standard Deviation 1 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 4 hour post-dose | 2.3 pg/mL | Standard Deviation 1.2 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α Pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 pre-dose | 76.5 pg/mL | Standard Deviation 59.8 |
| Cohort 2 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 24 hour post-dose | 5.9 pg/mL | Standard Deviation 3.9 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 4 hour post-dose | 38.3 pg/mL | Standard Deviation 51.9 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA pre-dose | 29.5 pg/mL | Standard Deviation 16.1 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 pre-dose | 8.1 pg/mL | Standard Deviation 4.7 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 24 hour post-dose | 16.7 pg/mL | Standard Deviation 8.2 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 24 hour post-dose | 4.5 pg/mL | Standard Deviation 1.2 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 4 hour post-dose | 1268.5 pg/mL | Standard Deviation 1733.8 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 4 hour post-dose | 57.1 pg/mL | Standard Deviation 64 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 pre-dose | 70.5 pg/mL | Standard Deviation 17.5 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 4 hour post | 933.1 pg/mL | Standard Deviation 427.2 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 24 hour post-dose | 6.3 pg/mL | Standard Deviation 6.6 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 pre-dose | 741.1 pg/mL | Standard Deviation 46.7 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 24 hour post-dose | 40.5 pg/mL | Standard Deviation 8.6 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α Pre-dose | 4.1 pg/mL | Standard Deviation 0.7 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 24 hour post-dose | 206.9 pg/mL | Standard Deviation 118.6 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 24 hour post | 939.3 pg/mL | Standard Deviation 939.3 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 4 hour post-dose | 15.9 pg/mL | Standard Deviation 16.6 |
| Cohort 3 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 4 hour post-dose | 718.8 pg/mL | Standard Deviation 872.8 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 24 hour post-dose | 184.6 pg/mL | Standard Deviation 22.7 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 24 hour post-dose | 3.3 pg/mL | Standard Deviation 2.9 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 4 hour post-dose | 89.8 pg/mL | Standard Deviation 144.5 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 4 hour post-dose | 133.7 pg/mL | Standard Deviation 228.7 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 4 hour post-dose | 3055.1 pg/mL | Standard Deviation 5286.2 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 24 hour post-dose | 9.8 pg/mL | Standard Deviation 1.5 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 24 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 pre-dose | 111.7 pg/mL | Standard Deviation 3.52 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 24 hour post-dose | 4.5 pg/mL | Standard Deviation 5.1 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA pre-dose | 2.8 pg/mL | Standard Deviation 2.1 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 pre-dose | 4.0 pg/mL | Standard Deviation 2.2 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 4 hour post-dose | 23.1 pg/mL | Standard Deviation 34.2 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α Pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 pre-dose | 574.3 pg/mL | Standard Deviation 341 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 4 hour post | 1316.7 pg/mL | Standard Deviation 1617.7 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 4 hour post-dose | 1202.5 pg/mL | Standard Deviation 1811.4 |
| Cohort 4 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 24 hour post | 667.7 pg/mL | Standard Deviation 362.7 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 pre-dose | 244.5 pg/mL | Standard Deviation 210.5 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α Pre-dose | 3.1 pg/mL | Standard Deviation 3 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 4 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 24 hour post-dose | 2.4 pg/mL | Standard Deviation 1.7 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 pre-dose | 670.2 pg/mL | Standard Deviation 369.4 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 4 hour post | 527.1 pg/mL | Standard Deviation 225.5 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 24 hour post | 541.8 pg/mL | Standard Deviation 240.9 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 4 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 24 hour post-dose | 3.8 pg/mL | Standard Deviation 3.8 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 pre-dose | 11.9 pg/mL | Standard Deviation 16.3 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 4 hour post-dose | 10.4 pg/mL | Standard Deviation 11.4 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA pre-dose | 26.5 pg/mL | Standard Deviation 42.7 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 4 hour post-dose | 5.4 pg/mL | Standard Deviation 8.6 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 24 hour post-dose | 9.0 pg/mL | Standard Deviation 16.6 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 24 hour post-dose | 25.8 pg/mL | Standard Deviation 37.2 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 4 hour post-dose | 160.2 pg/mL | Standard Deviation 117.7 |
| Cohort 5 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 24 hour post-dose | 316.6 pg/mL | Standard Deviation 198.4 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 24 hour post-dose | 26.1 pg/mL | Standard Deviation 11.2 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 4 hour post-dose | 13.2 pg/mL | Standard Deviation 11.1 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-8 pre-dose | 18.6 pg/mL | Standard Deviation 14.7 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 24 hour post-dose | 19.2 pg/mL | Standard Deviation 26.8 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α Pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 pre-dose | 164.4 pg/mL | Standard Deviation 134.1 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 4 hour post-dose | 4.7 pg/mL | Standard Deviation 5.3 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-6 pre-dose | 7.9 pg/mL | Standard Deviation 10.9 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 24 hour post | 830.7 pg/mL | Standard Deviation 333.3 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 4 hour post | 533.7 pg/mL | Standard Deviation 265.6 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 24 hour post-dose | 445.8 pg/mL | Standard Deviation 337.8 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | MCP-1 4 hour post-dose | 137.2 pg/mL | Standard Deviation 33.1 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-10 pre-dose | 599.7 pg/mL | Standard Deviation 333.8 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 24 hour post-dose | 3.8 pg/mL | Standard Deviation 3.8 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 4 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA pre-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | TNF-α 4 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
| Cohort 6 | DCR-MYC Biological Activities (Phase 1b Only) | IL-IRA 24 hour post-dose | 1.6 pg/mL | Standard Deviation 0 |
Secondary
Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Samples to be collected Week 1 (Day 1, 2, and 4) and Week 2 (Day 8 and 11). A summary of outcome measures reported here are noncompartmental PK parameters (Cmax, dose-normalized Cmax (Cmax\_D), Tmax, AUClast, and dose-normalized AUClast (AUClast\_D)) for both infusion days (Day 1 and Day 8).
Time frame: Week 1 Day 1 AND Week 2 Day 8 Cycle PK Sampling Points: 0 min, 1/4 through infusion, 1/2 through infusion, end of infusion, 15 min, 30 min, 1h, 2h, 4h, 6h, 8h, 24h, Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 1 | 2.4 hr | Standard Deviation 0.14 |
| Cohort 1 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 8 | 2.6 hr | Standard Deviation 0.6 |
| Cohort 2 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 1 | 2.7 hr | Standard Deviation 0.68 |
| Cohort 2 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 8 | 2.4 hr | Standard Deviation 0.13 |
| Cohort 3 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 1 | 2.6 hr | Standard Deviation 0.27 |
| Cohort 3 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 8 | 2.7 hr | Standard Deviation 0.35 |
| Cohort 4 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 1 | 2.9 hr | Standard Deviation 0.55 |
| Cohort 4 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 8 | 2.2 hr | Standard Deviation 0.24 |
| Cohort 5 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 1 | 2.3 hr | Standard Deviation 0.26 |
| Cohort 5 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 8 | 3.0 hr | Standard Deviation 0.72 |
| Cohort 6 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 1 | 2.2 hr | Standard Deviation 0.14 |
| Cohort 6 | Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8 | Tmax: Day 8 | 2.2 hr | Standard Deviation 0.24 |