Phase Ib/2, Multicenter, Dose Escalation Study of DCR-MYC in Patients With Hepatocellular Carcinoma

• Sponsor: Dicerna Pharmaceuticals, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02314052
• Collaborator: (none)
• Enrollment: 21
• Locations: 6
• Arm: 1
• Actual Duration (Months): 20.5
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: DCR-MYC	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1b/2, Multicenter, Dose Escalation Trial to Determine the Safety, Tolerance, Maximum Tolerated Dose and Recommended Phase 2 Dose of DCR-MYC, a Lipid Nanoparticle (LNP)-Formulated Small Inhibitory RNA (siRNA) Oligonucleotide Targeting MYC, in Patients With Hepatocellular Carcinoma (HCC)
• Actual Study Start Date: Jan 27, 2015
• Actual Primary Completion Date: Oct 11, 2016
• Actual Study Completion Date: Oct 11, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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

Drug: 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

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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.

3. 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 Outcome Measures

1. 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).

2. 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.

3. DCR-MYC Biological Activities (Phase 1b Only) [Cycle 1 and 2]

   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.

4. 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).

5. 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).

6. 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).

7. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

1. 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

1. Patients with the following coagulation parameter abnormality at baseline:

• INR > 1.7 × ULN for the institution

1. 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

1. 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

1. 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

1. 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).

2. Patients with an estimated daily alcohol intake greater than 80 g/day.

3. Patients having undergone previous organ transplantation (e.g., liver transplantation) requiring immunosuppression; patients on long-term immunosuppressive therapy.

4. Patients with a known history of human immunodeficiency virus (HIV) seropositivity.

5. 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.

6. Patients with inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy.

7. 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.

8. 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)

1. 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.

2. 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.

3. 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.

Exclusion Criteria (Treatments):

1. Phase 1b: Greater than 3 prior systemic anti-cancer chemotherapies or targeted agents for HCC; prior loco-regional treatment, including transcatheter arterial chemo-embolization (TACE), is allowed.

2. Phase 2: greater than 1 prior systemic anti-cancer chemotherapy or targeted agent for HCC; prior loco-regional treatment, including TACE, is allowed.

3. Sorafenib therapy within 2 weeks prior to first study drug administration and during study.

4. Any other antineoplastic agent (standard or experimental) within 4 weeks; monoclonal antibody therapy, nitrosoureas, and nitrogen mustard within 6 weeks prior to first study drug administration and during study.

5. Loco-regional therapy including TACE or radioembolization within 6 weeks prior to first study drug administration and during study.

6. Radiotherapy within 4 weeks prior to first study drug administration and during study.

7. Therapy with sofosbuvir for HCV within 6 weeks prior to first study drug administration and during study.

8. Herbal preparations, or related non-prescription preparations/supplements containing herbal ingredients, aimed at treating the underlying malignancy within 2 weeks prior to first study drug administration and during study.

9. Systemic hormonal therapy within 2 weeks prior to first study drug administration and during study.

10. Any other investigational treatments during study. This includes participation in any medical device or therapeutic intervention clinical trial.

11. Prophylactic use of hematopoietic growth factors within 1 week prior to first study drug administration and during Cycle 1 of study; thereafter prophylactic use of growth factors is allowed as clinically indicated.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259-5499
2	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
3	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas	United States	78229
4	Asan Medical Center	Seoul		Korea, Republic of	138-736
5	National University Hospital of Singapore	Singapore		Singapore	119228
6	National Cancer Centre Singapore	Singapore		Singapore	169610

Sponsors and Collaborators

• Dicerna Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dicerna Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02314052
• Other Study ID Numbers: DCR-MYC-102
• First Posted: Dec 10, 2014
• Last Update Posted: Sep 4, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Period Title: Cycle One
STARTED	3	3	3	3	6	3
COMPLETED	3	3	3	2	6	3
NOT COMPLETED	0	0	0	1	0	0
Period Title: Cycle One
STARTED	3	3	3	2	6	3
COMPLETED	3	2	2	1	2	3
NOT COMPLETED	0	1	1	1	4	0
Period Title: Cycle One
STARTED	3	2	2	1	2	3
COMPLETED	3	2	2	1	2	3
NOT COMPLETED	0	0	0	0	0	0
Period Title: Cycle One
STARTED	3	2	2	1	2	3
COMPLETED	0	2	1	0	2	0
NOT COMPLETED	3	0	1	1	0	3
Period Title: Cycle One
STARTED	0	2	1	1	2	0
COMPLETED	0	0	0	1	2	0
NOT COMPLETED	0	2	1	0	0	0
Period Title: Cycle One
STARTED	0	0	0	1	2	0
COMPLETED	0	0	0	1	2	0
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	DCR-MYC
Arm/Group Description	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
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 57.1%
>=65 years	9 42.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.1 (7.24)
Sex: Female, Male (Count of Participants)
Female	2 9.5%
Male	19 90.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	15 71.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	5 23.8%
More than one race	0 0%
Unknown or Not Reported	1 4.8%
Region of Enrollment (Count of Participants)
South Korea	8 38.1%
Singapore	7 33.3%
United States	6 28.6%

Outcome Measures

1. Primary Outcome

Title	Phase 1b: Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Description	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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	3	3	3	3	6	3
Count of Participants [Participants]	3 14.3%	3 NaN	3 NaN	3 NaN	6 NaN	3 NaN

2. Primary Outcome

Title	Phase 2: Patients With Adverse Events as a Measure of Safety and Tolerability
Description	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

Outcome Measure Data

Analysis Population Description

N/A - Study terminated prior to Phase 2

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	0	0	0	0	0	0

3. Primary Outcome

Title	Phase 2: Preliminary Antitumor Activity
Description	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

Outcome Measure Data

Analysis Population Description

N/A - Study terminated prior to phase 2

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	0	0	0	0	0	0

4. Secondary Outcome

Title	Cmax (ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	3	3	3	3	6	3
Cmax: Day 1	2094.3 (1257.8)	4790.5 (3540.2)	6195.7 (744.75)	9807.1 (4094.5)	19399 (8211.4)	19829 (3686.2)
Cmax: Day 8	1755.7 (59.47)	5504.9 (3365.3)	6628.4 (1155.8)	13484 (2576.2)	20711 (13768)	27067 (9105.1)

5. Secondary Outcome

Title	DCR-MYC Biological Activities (Phase 1b Only)
Description	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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	3	3	3	3	6	3
TNF-α Pre-dose	2.3 (1.3)	1.6 (0)	4.1 (0.7)	1.6 (0)	3.1 (3.0)	1.6 (0)
TNF-α 4 hour post-dose	1.6 (0)	1.6 (0)	15.9 (16.6)	23.1 (34.2)	1.6 (0)	1.6 (0)
TNF-α 24 hour post-dose	1.6 (0)	4.1 (0.5)	4.5 (1.2)	3.3 (2.9)	2.4 (1.7)	3.8 (3.8)
IL-10 pre-dose	317.5 (60.9)	239.4 (83.7)	741.1 (46.7)	574.3 (341.0)	670.2 (369.4)	599.7 (333.8)
IL-10 4 hour post	241.1 (61.3)	159.6 (104.2)	933.1 (427.2)	1316.7 (1617.7)	527.1 (225.5)	533.7 (265.6)
IL-10 24 hour post	322.5 (152.9)	424.4 (296.4)	939.3 (939.3)	667.7 (362.7)	541.8 (240.9)	830.7 (333.3)
IL-6 pre-dose	1.6 (0)	1.6 (0)	1.6 (0)	1.6 (0)	1.6 (0)	7.9 (10.9)
IL-6 4 hour post-dose	1.6 (0)	1.6 (0)	38.3 (51.9)	133.7 (228.7)	1.6 (0)	4.7 (5.3)
IL-6 24 hour post-dose	2.2 (1.0)	1.6 (0)	6.3 (6.6)	1.6 (0)	3.8 (3.8)	19.2 (26.8)
IL-8 pre-dose	8.7 (2.7)	2.2 (1.0)	8.1 (4.7)	4.0 (2.2)	11.9 (16.3)	18.6 (14.7)
IL-8 4 hour post-dose	8.2 (3.1)	2.3 (1.2)	57.1 (64.0)	89.8 (144.5)	10.4 (11.4)	13.2 (11.1)
IL-8 24 hour post-dose	9.0 (2.8)	5.9 (3.9)	16.7 (8.2)	9.8 (1.5)	25.8 (37.2)	26.1 (11.2)
IL-IRA pre-dose	10.2 (7.7)	26.4 (26.3)	29.5 (16.1)	2.8 (2.1)	26.5 (42.7)	1.6 (0)
IL-IRA 4 hour post-dose	4.1 (4.3)	3.3 (2.9)	1268.5 (1733.8)	3055.1 (5286.2)	5.4 (8.6)	1.6 (0)
IL-IRA 24 hour post-dose	5.3 (6.4)	13.3 (10.2)	40.5 (8.6)	4.5 (5.1)	9.0 (16.6)	1.6 (0)
MCP-1 pre-dose	101.2 (13.1)	76.5 (59.8)	70.5 (17.5)	111.7 (3.52)	244.5 (210.5)	164.4 (134.1)
MCP-1 4 hour post-dose	90.0 (18.8)	46.0 (23.6)	718.8 (872.8)	1202.5 (1811.4)	160.2 (117.7)	137.2 (33.1)
MCP-1 24 hour post-dose	162.1 (69.8)	119.5 (69.0)	206.9 (118.6)	184.6 (22.7)	316.6 (198.4)	445.8 (337.8)

6. Secondary Outcome

Title	DCR-MYC Biological Activities (Phase 1b Only)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	0	0	0	0	0	0

7. Secondary Outcome

Title	Tmax (Hr) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	3	3	3	3	6	3
Tmax: Day 1	2.4 (0.14)	2.7 (0.68)	2.6 (0.27)	2.9 (0.55)	2.3 (0.26)	2.2 (0.14)
Tmax: Day 8	2.6 (0.60)	2.4 (0.13)	2.7 (0.35)	2.2 (0.24)	3.0 (0.72)	2.2 (0.24)

8. Secondary Outcome

Title	Cmax_D (kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	3	3	3	33	6	3
Cmax_D: Day 1	16832 (10192)	23952 (17701)	20652 (2482.5)	21794 (9098.8)	28527 (12076)	23384 (4241.4)
Cmax_D: Day 8	14045 (475.74)	27525 (16827)	22095 (3852.7)	29964 (5724.8)	30457 (20247)	31931 (10677)

9. Secondary Outcome

Title	AUClast_D (hr*kg*ng/mL/mg) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	3	3	3	3	6	3
AUClast_D: Day 1	178997 (125460)	299295 (312426)	197244 (116908)	195133 (56544)	290201 (169069)	201529 (45290)
AUClast_D: Day 8	163478 (109924)	739203 (698459)	389653 (293467)	350625 (132910)	274941 (168548)	383537 (84286)

10. Secondary Outcome

Title	AUClast (hr*ng/mL) - DCR-MYC Levels in Blood (Phase 1b Only): Dosing Day 1 and Day 8
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.	N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined five 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
Measure Participants	3	3	3	3	6	3
AUClast : Day 1	22375 (15683)	59859 (62485)	59173 (35072)	87810 (25445)	197337 (114967)	171299 (38496)
AUClast : Day 8	20435 (13741)	147841 (139692)	116896 (88040)	157781 (59810)	186960 (114612)	326006 (71643)

Adverse Events

Time Frame	Throughout entire duration of the study (e.g., approximately 3 month period)
Arm/Group Title	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5		Cohort 6
Arm/Group Description	N = 3, received two, 2-hour infusions of 0.125 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.		N = 3, received two, 2-hour infusions of 0.2 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.		N = 3, received two, 2-hour infusions of 0.3 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.		N = 3, received two, 2-hour infusions of 0.45 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.		N = 6, received two, 2-hour infusions of 0.68 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.		N = 3, received two, 2-hour infusions of 0.85 mg/kg DCR-MYC, once on Day 1 and once on Day 8 within a 21-day cycle. The protocol outlined 5 21-day cycles, each with dosing on days 1 and 8. The study was terminated prematurely and subjects were not treated after the termination date.
All Cause Mortality
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5		Cohort 6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		0/3 (0%)		3/3 (100%)		1/3 (33.3%)		3/6 (50%)		2/3 (66.7%)
Serious Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5		Cohort 6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		2/6 (33.3%)		1/3 (33.3%)
Cardiac disorders
Acute coronary syndrome/ Acute Coronary Syndrome	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
General disorders
Influenza like illness/ Flu Like Symptom	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Hepatobiliary disorders
Cholangitis/ Cholangitis Due To Pd	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone/ Osteolytic Jaw Lesion Due To Progression Disease	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Nervous system disorders
Spinal cord compression/ Spinal Cord Compression Due To Pathologic Fracture Of T1	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain/ Sore Throat	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dyspnoea/ Increased Dyspnea	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/6 (0%)	0	0/3 (0%)	0
Vascular disorders
Hypovolaemic shock/ Hypovolemic Hypoperfusion	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5		Cohort 6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		6/6 (100%)		3/3 (100%)
Gastrointestinal disorders
Diarrhoea	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)
Ascites	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		1/3 (33.3%)
Abdominal distention	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)
Dyspepsia	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)
Nausea	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)
Vomiting	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)
General disorders
Fatigue	0/3 (0%)		1/3 (33.3%)		2/3 (66.7%)		2/3 (66.7%)		1/6 (16.7%)		2/3 (66.7%)
Oedema peripheral	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		2/6 (33.3%)		2/3 (66.7%)
Pyrexia	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/6 (16.7%)		0/3 (0%)
Chills	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)
Influenza-like illness	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)
Pain	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)
Investigations
AST increased	1/3 (33.3%)		0/3 (0%)		2/3 (66.7%)		1/3 (33.3%)		1/6 (16.7%)		1/3 (33.3%)
ALT increased	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)
Lipase increased	1/3 (33.3%)		2/3 (66.7%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)
Blood bilirubin increased	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/6 (16.7%)		1/3 (33.3%)
Blood creatinine increased	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)
GGT increased	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/6 (0%)		0/3 (0%)
Platelet count decreased	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/6 (33.3%)		0/3 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/3 (66.7%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/6 (16.7%)		0/3 (0%)
Hyperglycaemia	0/3 (0%)		1/3 (33.3%)		2/3 (66.7%)		0/3 (0%)		0/6 (0%)		1/3 (33.3%)
Hypophosphataemia	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/6 (0%)		1/3 (33.3%)

Limitations/Caveats

The study was prematurely discontinued by the Sponsor because of evolving data from a separate study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

SPONSOR agrees that the Principal Investigator shall have the right to publish or permit the publication of any information or material relating to or arising out of the work after prior submittal to SPONSOR provided that if SPONSOR shall so request, the investigator will delay publication for a maximum of ninety (90) days after submittal to SPONSOR to enable SPONSOR to protect its rights. SPONSOR will comment on such documents within thirty (30) days.