Long-term Safety and Efficacy of Momelotinib in Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia

• Sponsor: Sierra Oncology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02124746
• Collaborator: (none)
• Enrollment: 87
• Locations: 22
• Arms: 4
• Actual Duration (Months): 55.2
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This open-label study is to determine the long-term safety and tolerability of momelotinib in previously enrolled study participants with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), post-essential thrombocythemia myelofibrosis (post-ET MF), polycythemia vera (PV), or essential thrombocythemia (ET), who have tolerated and achieved stable disease or better with momelotinib treatment while enrolled in a previous clinical trial.

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia	Drug: Momelotinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label Study to Assess the Long-term Safety and Efficacy of Momelotinib in Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia
• Actual Study Start Date: Apr 30, 2014
• Actual Primary Completion Date: Dec 6, 2018
• Actual Study Completion Date: Dec 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Participants previously enrolled in Study CCL09191E will receive momelotinib for approximately 4 years.	Drug: Momelotinib; Momelotinib tablets administered orally once daily; Other Names: GS-0387 CYT387
Experimental: Cohort 2 Participants previously enrolled in Study YM387-II-02 will receive momelotinib for approximately 4 years.	Drug: Momelotinib; Momelotinib tablets administered orally once daily; Other Names: GS-0387 CYT387
Experimental: Cohort 3 Participants previously enrolled in Study GS-US-354-0101 will receive momelotinib for up to 4 years. Cohort 3 was closed and all enrolled participants were discontinued from this study because parent Study GS-US-354-0101 was terminated.	Drug: Momelotinib; Momelotinib tablets administered orally once daily; Other Names: GS-0387 CYT387
Experimental: Cohort 4 Participants previously enrolled in Study GS-US-352-1672 will receive momelotinib for approximately 4 years.	Drug: Momelotinib; Momelotinib tablets administered orally once daily; Other Names: GS-0387 CYT387

Outcome Measures

Primary Outcome Measures

1. Long Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities [From the first dose of momelotinib in the parent study to 30 days following permanent discontinuation of momelotinib in Study GS-US-352-1154.]

   Long-term safety and tolerability profile of momelotinib based on safety data (adverse events and selected hematology and chemistry laboratory parameters) collected after the first dose of momelotinib in the parent study.

Secondary Outcome Measures

1. Splenic Response Rate [From baseline in the parent study until the last spleen assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.]

   The number of subjects achieving a spleen response, defined as a reduction of 50% or more in palpable splenomegaly of a spleen that was at least 10 cm below the LCM at baseline, or a spleen that was palpable at > 5 cm and < 10 cm below the LCM at baseline becoming not palpable for at least 56 days, using baseline of the parent study as the reference.

2. Duration of Splenic Response [From baseline in the parent study until the last spleen assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.]

   The interval from the first onset of splenic response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of splenic response. Loss of response was defined as the reduction of splenomegaly by < 50% among responders (with splenomegaly ≥ 10 cm below the LCM at baseline) that lasts ≥ 56 days, or the recurrence of > 0 cm splenomegaly among responders (with splenomegaly > 5 and < 10 cm at baseline) that lasts ≥ 56 days. Duration of splenic response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.

3. Transfusion Independence Response Rate [From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.]

   The number of transfusion dependent subjects at entry to a parent study who became transfusion-independent for ≥ 12 weeks at any time from the first dose of momelotinib in the parent study until the end of Study GS-US-352-1154.

4. Duration of Transfusion Independence Response [From baseline in the parent study until the last assessment date in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.]

   The interval from the first onset date of transfusion independence (in the parent study or Study GS-US-352-1154) to the earliest date of loss of response for participants who are transfusion dependent at baseline in the parent study. Loss of TI response was defined as receiving an RBC transfusion after achieving a TI response. Duration of transfusion independence response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.

5. Anemia Response Rate [From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.]

   The number of subjects achieving an anemia response, defined as: Achieving transfusion independence for ≥ 12 weeks, for subjects who were transfusion-dependent at baseline in the parent study, or Having ≥ 2 g/dL increase in Hgb from baseline for ≥ 12 weeks, for subjects with Hgb < 10 g/dL at baseline in the parent study who were not transfusion-dependent (Cohort 1) or who were transfusion-independent (Cohort 2).

6. Duration of Anemia Response [From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.]

   The interval from the first onset of anemia response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of anemia response. Loss of anemia response was defined as having any RBC transfusion after achieving an anemia response. Duration of anemia response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.

7. Rate of RBC Transfusion [From the first dose of momelotinib in the parent study until the last dose of momelotinib in Study GS-US-352-1154.]

   The average number of RBC units per subject month during the parent study and/or Study GS-US-352-1154.

8. Overall Survival [From baseline in the parent study until the date of last contact or last response assessment, up to 30 days following permanent discontinuation of momelotinib.]

   The interval from the first dose of momelotinib in the parent study until death from any cause. Overall survival was analyzed using the Kaplan-Meier method. Data from subjects who were lost to follow-up or remained alive until the end of the study were censored at the date of last contact or last response assessment.

9. Progression-Free Survival [From baseline in the parent study until the last response assessment, up to 30 days following permanent discontinuation of momelotinib.]

   The interval from the first dose of momelotinib in the parent study until the first documentation of definitive progressive disease as defined in 2006 IWG-MRT or death due to any cause. Subjects who were free of progression were censored at the last assessment date.

10. Leukemia-Free Survival [From baseline in the parent study until the date of the last assessment, up to 30 days following permanent discontinuation of momelotinib.]

    The interval from the first dose of momelotinib in the parent study until the first documented leukemic transformation or death from any cause. Leukemic transformation was documented in the adverse event electronic case report form. Leukemia-free survival was analyzed using the Kaplan-Meier method. Subjects who were free of leukemia transformation were censored at the last assessment date.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Currently enrolled in study CCL09101E, or YM387-II-02, or successfully completed 24 weeks of study GS-US-352-1672

• Able to comprehend and willing to sign informed consent form

Key Exclusion Criteria:

• Known hypersensitivity to momelotinib, its metabolites, or formulation excipients

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Scottsdale	Arizona	United States
2		Orange	California	United States
3		Stanford	California	United States
4		Whittier	California	United States
5		Jacksonville	Florida	United States
6		Baltimore	Maryland	United States
7		Boston	Massachusetts	United States
8		Ann Arbor	Michigan	United States
9		Rochester	Minnesota	United States
10		Saint Louis	Missouri	United States
11		Bronx	New York	United States
12		New York	New York	United States
13		Cleveland	Ohio	United States
14		Houston	Texas	United States
15		Salt Lake City	Utah	United States
16		Frankston	Victoria	Australia
17		Parkville	Victoria	Australia
18		Toronto	Ontario	Canada
19		Montreal	Quebec	Canada
20		La Tronche		France
21		Paris		France
22		Minden		Germany

Sponsors and Collaborators

• Sierra Oncology, Inc.

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Nov 6, 2017
• Statistical Analysis Plan - Apr 26, 2019

More Information

Publications

None provided.

• Responsible Party: Sierra Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02124746
• Other Study ID Numbers: GS-US-352-1154; 2013-004476-36
• First Posted: Apr 28, 2014
• Last Update Posted: Feb 5, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sierra Oncology, Inc.: Primary Myelofibrosis; Post Polycythemia Vera Myelofibrosis; Post Essential Thrombocythemia Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia; blood disorders
• Additional relevant MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Study Results

Participant Flow

Recruitment Details	Benefiting subjects enrolled in 1 of 3 prior momelotinib (MMB) studies (parent studies) for the treatment of MF were included for continued dosing of MMB. Cohort 3 (PV/ET; n=13) was closed and subjects were discontinued due to limited efficacy of MMB in the treatment of PV/ET observed in the parent study. Cohort 3 was excluded from all analyses.

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.
Period Title: Overall Study
STARTED	30	22	22
COMPLETED	11	4	0
NOT COMPLETED	19	18	22

Baseline Characteristics

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	Total of all reporting groups
Overall Participants	30	22	22	74
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66.0	64.0	68.0	66.5
Sex: Female, Male (Count of Participants)
Female	17 56.7%	10 45.5%	9 40.9%	36 48.6%
Male	13 43.3%	12 54.5%	13 59.1%	38 51.4%
Race/Ethnicity, Customized (Count of Participants)
White	26 86.7%	20 90.9%	18 81.8%	64 86.5%
Black or African American	0 0%	2 9.1%	2 9.1%	4 5.4%
Asian	2 6.7%	0 0%	0 0%	2 2.7%
Hispanic or Latino	1 3.3%	0 0%	0 0%	1 1.4%
Other	1 3.3%	0 0%	2 9.1%	3 4.1%
Transfusion Dependent (at baseline in parent study) (Count of Participants)
Yes	7 23.3%	7 31.8%	22 100%	36 48.6%
No	23 76.7%	12 54.5%	0 0%	35 47.3%
Missing	0 0%	3 13.6%	0 0%	3 4.1%

Outcome Measures

1. Primary Outcome

Title	Long Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities
Description	Long-term safety and tolerability profile of momelotinib based on safety data (adverse events and selected hematology and chemistry laboratory parameters) collected after the first dose of momelotinib in the parent study.
Time Frame	From the first dose of momelotinib in the parent study to 30 days following permanent discontinuation of momelotinib in Study GS-US-352-1154.

Outcome Measure Data

Analysis Population Description

It was pre-specified that safety outcomes would be analyzed and summarized by starting dose in Study GS-US-352-1154. Therefore data for this outcome measure are presented for the total subjects enrolled to Study GS-US-352-1154 and not by cohort.

Arm/Group Title	Total
Arm/Group Description	All subjects enrolled to Study GS-US-352-1154
Measure Participants	74
Subjects with ≥ one AE (any grade)	73 243.3%
Subjects with ≥ one Grade 3 or higher AE	62 206.7%
Subjects with Grade 3 lab toxicity (highest grade)	36 120%
Subjects with Grade 4 lab toxicity (highest grade)	16 53.3%

2. Secondary Outcome

Title	Splenic Response Rate
Description	The number of subjects achieving a spleen response, defined as a reduction of 50% or more in palpable splenomegaly of a spleen that was at least 10 cm below the LCM at baseline, or a spleen that was palpable at > 5 cm and < 10 cm below the LCM at baseline becoming not palpable for at least 56 days, using baseline of the parent study as the reference.
Time Frame	From baseline in the parent study until the last spleen assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

Subjects with splenomegaly >5 cm at baseline in the parent studies who were enrolled in Study GS-US-352-1154 were evaluable for splenic response assessment.

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	25	21	17	63
Count of Participants [Participants]	20 66.7%	19 86.4%	6 27.3%	45 60.8%

3. Secondary Outcome

Title	Duration of Splenic Response
Description	The interval from the first onset of splenic response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of splenic response. Loss of response was defined as the reduction of splenomegaly by < 50% among responders (with splenomegaly ≥ 10 cm below the LCM at baseline) that lasts ≥ 56 days, or the recurrence of > 0 cm splenomegaly among responders (with splenomegaly > 5 and < 10 cm at baseline) that lasts ≥ 56 days. Duration of splenic response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Time Frame	From baseline in the parent study until the last spleen assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

Duration of splenic response was assessed for spleen responders who enrolled in Study GS-US-352-1154 only.

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	20	19	6	45
Median (Inter-Quartile Range) [days]	1704.5	736.0	447.5	990.0

4. Secondary Outcome

Title	Transfusion Independence Response Rate
Description	The number of transfusion dependent subjects at entry to a parent study who became transfusion-independent for ≥ 12 weeks at any time from the first dose of momelotinib in the parent study until the end of Study GS-US-352-1154.
Time Frame	From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

Subjects who were transfusion dependent at baseline in the parent studies and were enrolled in Study GS-US-352-1154 were evaluable for transfusion independence response.

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	7	7	22	36
Count of Participants [Participants]	7 23.3%	5 22.7%	16 72.7%	28 37.8%

5. Secondary Outcome

Title	Duration of Transfusion Independence Response
Description	The interval from the first onset date of transfusion independence (in the parent study or Study GS-US-352-1154) to the earliest date of loss of response for participants who are transfusion dependent at baseline in the parent study. Loss of TI response was defined as receiving an RBC transfusion after achieving a TI response. Duration of transfusion independence response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Time Frame	From baseline in the parent study until the last assessment date in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

Duration of transfusion independence response was assessed for transfusion independence responders who were enrolled in Study GS-US-352-1154.

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	7	5	16	28
Median (Inter-Quartile Range) [days]	357.0	114.0	281.5	193.5

6. Secondary Outcome

Title	Anemia Response Rate
Description	The number of subjects achieving an anemia response, defined as: Achieving transfusion independence for ≥ 12 weeks, for subjects who were transfusion-dependent at baseline in the parent study, or Having ≥ 2 g/dL increase in Hgb from baseline for ≥ 12 weeks, for subjects with Hgb < 10 g/dL at baseline in the parent study who were not transfusion-dependent (Cohort 1) or who were transfusion-independent (Cohort 2).
Time Frame	From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

Subjects who were anemia response-evaluable at baseline in the parent studies and were enrolled in Study GS-US-352-1154 were evaluable for anemia response.

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	18	12	22	52
Count of Participants [Participants]	13 43.3%	6 27.3%	16 72.7%	35 47.3%

7. Secondary Outcome

Title	Duration of Anemia Response
Description	The interval from the first onset of anemia response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of anemia response. Loss of anemia response was defined as having any RBC transfusion after achieving an anemia response. Duration of anemia response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Time Frame	From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

Duration of anemia response was assessed for anemia responders who were enrolled in Study GS-US-352-1154.

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	13	6	16	35
Median (Inter-Quartile Range) [days]	995.0	120.0	281.5	358.0

8. Secondary Outcome

Title	Rate of RBC Transfusion
Description	The average number of RBC units per subject month during the parent study and/or Study GS-US-352-1154.
Time Frame	From the first dose of momelotinib in the parent study until the last dose of momelotinib in Study GS-US-352-1154.

Outcome Measure Data

Analysis Population Description

It was pre-specified that safety outcomes would be analyzed and summarized by starting dose in Study GS-US-352-1154. Therefore data for this outcome measure are presented for the total subjects enrolled to Study GS-US-352-1154 and not by cohort.

Arm/Group Title	Total
Arm/Group Description	All subjects enrolled to Study GS-US-352-1154
Measure Participants	74
RBC Transfusion Rate in Parent Studies	0.08
RBC Transfusion Rate in Study GS-US-352-1154	0.00
RBC Transfusion Rate Since 1st Dose in ParentStudy	0.06

9. Secondary Outcome

Title	Overall Survival
Description	The interval from the first dose of momelotinib in the parent study until death from any cause. Overall survival was analyzed using the Kaplan-Meier method. Data from subjects who were lost to follow-up or remained alive until the end of the study were censored at the date of last contact or last response assessment.
Time Frame	From baseline in the parent study until the date of last contact or last response assessment, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	30	22	22	74
Median (Full Range) [months]	NA	NA	NA	NA

10. Secondary Outcome

Title	Progression-Free Survival
Description	The interval from the first dose of momelotinib in the parent study until the first documentation of definitive progressive disease as defined in 2006 IWG-MRT or death due to any cause. Subjects who were free of progression were censored at the last assessment date.
Time Frame	From baseline in the parent study until the last response assessment, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	30	22	22	74
Median (95% Confidence Interval) [months]	NA	NA	NA	NA

11. Secondary Outcome

Title	Leukemia-Free Survival
Description	The interval from the first dose of momelotinib in the parent study until the first documented leukemic transformation or death from any cause. Leukemic transformation was documented in the adverse event electronic case report form. Leukemia-free survival was analyzed using the Kaplan-Meier method. Subjects who were free of leukemia transformation were censored at the last assessment date.
Time Frame	From baseline in the parent study until the date of the last assessment, up to 30 days following permanent discontinuation of momelotinib.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)	Cohort 2 (YM387-II-02/GS-US-352-1154)	Cohort 4 (GS-US-352-1672/GS-US-352-1154)	Total
Arm/Group Description	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.	Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.	All subjects enrolled to Study GS-US-352-1154
Measure Participants	30	22	22	74
Median (Full Range) [months]	NA	NA	NA	NA

Adverse Events

Time Frame	From the first dose of momelotinib in the parent study until 30 days after the last dose in Study GS-US-352-1154.
Adverse Event Reporting Description	Treatment-emergent AEs were defined as AEs with onset dates on or after the start of study drug in the parent study and no later than 30 days after permanent discontinuation of study drug, or any AEs leading to premature discontinuation of study drug. It was pre-specified that adverse event data would be analyzed and summarized by starting dose in Study GS-US-352-1154. Therefore adverse event data are presented for the total subjects enrolled to Study GS-US-352-1154 and not by cohort.
Arm/Group Title	Total
Arm/Group Description	All subjects enrolled to Study GS-US-352-1154
All Cause Mortality
	Total
	Affected / at Risk (%)	# Events
Total	8/74 (10.8%)
Serious Adverse Events
	Total
	Affected / at Risk (%)	# Events
Total	49/74 (66.2%)
Blood and lymphatic system disorders
Anaemia	1/74 (1.4%)
Febrile neutropenia	2/74 (2.7%)
Neutropenia	1/74 (1.4%)
Thrombocytopenia	2/74 (2.7%)
Cardiac disorders
Angina pectoris	2/74 (2.7%)
Aortic valve disease	1/74 (1.4%)
Atrial fibrillation	1/74 (1.4%)
Atrial flutter	1/74 (1.4%)
Atrioventricular block	1/74 (1.4%)
Cardiac failure	1/74 (1.4%)
Cardiac failure acute	1/74 (1.4%)
Cardiac failure congestive	4/74 (5.4%)
Cardiomyopathy	1/74 (1.4%)
Myocardial infarction	1/74 (1.4%)
Myocardial ischaemia	2/74 (2.7%)
Palpitations	1/74 (1.4%)
Sinus node dysfunction	1/74 (1.4%)
Ventricular tachycardia	1/74 (1.4%)
Gastrointestinal disorders
Abdominal pain	6/74 (8.1%)
Ascites	1/74 (1.4%)
Colitis	1/74 (1.4%)
Constipation	1/74 (1.4%)
Diarrhoea	1/74 (1.4%)
Gastrointestinal haemorrhage	1/74 (1.4%)
Haematochezia	1/74 (1.4%)
Mouth haemorrhage	1/74 (1.4%)
Salivary gland enlargement	1/74 (1.4%)
Small intestinal obstruction	2/74 (2.7%)
Varices oesophageal	1/74 (1.4%)
General disorders
Asthenia	2/74 (2.7%)
Chest pain	1/74 (1.4%)
Death	1/74 (1.4%)
Pain	1/74 (1.4%)
Pyrexia	2/74 (2.7%)
Hepatobiliary disorders
Cholecystitis chronic	1/74 (1.4%)
Infections and infestations
Appendicitis	2/74 (2.7%)
Bacterial infection	1/74 (1.4%)
Bronchitis	1/74 (1.4%)
Cellulitis	1/74 (1.4%)
Clostridium difficile colitis	1/74 (1.4%)
Gastroenteritis	1/74 (1.4%)
Gastroenteritis escherichia coli	1/74 (1.4%)
Infection	1/74 (1.4%)
Localised infection	1/74 (1.4%)
Lung infection	4/74 (5.4%)
Peritonitis	1/74 (1.4%)
Pharyngitis	1/74 (1.4%)
Pneumococcal sepsis	1/74 (1.4%)
Pneumonia	7/74 (9.5%)
Pneumonia klebsiella	1/74 (1.4%)
Pneumonia pneumococcal	1/74 (1.4%)
Pyelonephritis	1/74 (1.4%)
Respiratory syncytial virus infection	1/74 (1.4%)
Sepsis	3/74 (4.1%)
Sinusitis bacterial	1/74 (1.4%)
Systemic mycosis	1/74 (1.4%)
Upper respiratory tract infection	1/74 (1.4%)
Urinary tract infection	3/74 (4.1%)
Injury, poisoning and procedural complications
Craniocerebral injury	1/74 (1.4%)
Fall	1/74 (1.4%)
Subdural haematoma	1/74 (1.4%)
Tendon injury	1/74 (1.4%)
Tibia fracture	1/74 (1.4%)
Investigations
Blood creatinine increased	1/74 (1.4%)
Ejection fraction decreased	1/74 (1.4%)
Metabolism and nutrition disorders
Dehydration	1/74 (1.4%)
Hypokalaemia	1/74 (1.4%)
Metabolic acidosis	1/74 (1.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/74 (1.4%)
Back pain	1/74 (1.4%)
Bone pain	1/74 (1.4%)
Muscular weakness	1/74 (1.4%)
Myalgia	1/74 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/74 (1.4%)
Mantle cell lymphoma	1/74 (1.4%)
Non-hodgkin's lymphoma	1/74 (1.4%)
Ovarian cancer	1/74 (1.4%)
Nervous system disorders
Cerebral haemorrhage	1/74 (1.4%)
Dizziness	1/74 (1.4%)
Intracranial venous sinus thrombosis	1/74 (1.4%)
Ischaemic stroke	1/74 (1.4%)
Syncope	1/74 (1.4%)
Transient global amnesia	1/74 (1.4%)
Wernicke's encephalopathy	1/74 (1.4%)
Psychiatric disorders
Delirium	1/74 (1.4%)
Renal and urinary disorders
Acute kidney injury	5/74 (6.8%)
Haematuria	1/74 (1.4%)
Nephrolithiasis	1/74 (1.4%)
Proteinuria	1/74 (1.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/74 (4.1%)
Pulmonary embolism	3/74 (4.1%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/74 (1.4%)
Vascular disorders
Deep vein thrombosis	1/74 (1.4%)
Hypotension	2/74 (2.7%)
Thrombosis	1/74 (1.4%)
Other (Not Including Serious) Adverse Events
	Total
	Affected / at Risk (%)	# Events
Total	73/74 (98.6%)
Blood and lymphatic system disorders
Anaemia	27/74 (36.5%)
Leukocytosis	7/74 (9.5%)
Leukopenia	9/74 (12.2%)
Neutropenia	17/74 (23%)
Thrombocytopenia	28/74 (37.8%)
Thrombocytosis	4/74 (5.4%)
Cardiac disorders
Atrial fibrillation	4/74 (5.4%)
Pericardial effusion	4/74 (5.4%)
Sinus bradycardia	7/74 (9.5%)
Ear and labyrinth disorders
Ear discomfort	4/74 (5.4%)
Eye disorders
Cataract	9/74 (12.2%)
Dry eye	8/74 (10.8%)
Lacrimation increased	4/74 (5.4%)
Vision blurred	7/74 (9.5%)
Gastrointestinal disorders
Abdominal pain	23/74 (31.1%)
Abdominal pain upper	4/74 (5.4%)
Constipation	19/74 (25.7%)
Diarrhoea	41/74 (55.4%)
Dyspepsia	8/74 (10.8%)
Gastrooesophageal reflux disease	5/74 (6.8%)
Nausea	33/74 (44.6%)
Vomiting	21/74 (28.4%)
General disorders
Asthenia	5/74 (6.8%)
Chest pain	7/74 (9.5%)
Chills	4/74 (5.4%)
Fatigue	35/74 (47.3%)
Influenza like illness	4/74 (5.4%)
Oedema peripheral	19/74 (25.7%)
Pain	6/74 (8.1%)
Pyrexia	16/74 (21.6%)
Infections and infestations
Bronchitis	7/74 (9.5%)
Herpes zoster	4/74 (5.4%)
Influenza	8/74 (10.8%)
Lung infection	6/74 (8.1%)
Sinusitis	14/74 (18.9%)
Upper respiratory tract infection	14/74 (18.9%)
Urinary tract infection	23/74 (31.1%)
Injury, poisoning and procedural complications
Contusion	22/74 (29.7%)
Fall	8/74 (10.8%)
Foot fracture	4/74 (5.4%)
Investigations
Activated partial thromboplastin time prolonged	5/74 (6.8%)
Alanine aminotransferase increased	19/74 (25.7%)
Amylase increased	12/74 (16.2%)
Aspartate aminotransferase increased	11/74 (14.9%)
Blood alkaline phosphatase increased	5/74 (6.8%)
Blood bilirubin increased	8/74 (10.8%)
Blood creatinine increased	17/74 (23%)
Blood uric acid increased	4/74 (5.4%)
Electrocardiogram QT prolonged	4/74 (5.4%)
Gamma-glutamyltransferase increased	4/74 (5.4%)
International normalised ratio increased	5/74 (6.8%)
Lipase increased	15/74 (20.3%)
Lymphocyte count decreased	4/74 (5.4%)
Neutrophil count decreased	5/74 (6.8%)
Platelet count decreased	11/74 (14.9%)
Weight decreased	8/74 (10.8%)
Weight increased	4/74 (5.4%)
White blood cell count decreased	5/74 (6.8%)
Metabolism and nutrition disorders
Decreased appetite	10/74 (13.5%)
Dehydration	5/74 (6.8%)
Hyperglycaemia	8/74 (10.8%)
Hyperkalaemia	11/74 (14.9%)
Hyperuricaemia	18/74 (24.3%)
Hypocalcaemia	4/74 (5.4%)
Hypokalaemia	6/74 (8.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	21/74 (28.4%)
Back pain	12/74 (16.2%)
Bone pain	8/74 (10.8%)
Muscle spasms	5/74 (6.8%)
Muscular weakness	8/74 (10.8%)
Musculoskeletal pain	5/74 (6.8%)
Myalgia	6/74 (8.1%)
Neck pain	4/74 (5.4%)
Pain in extremity	18/74 (24.3%)
Nervous system disorders
Dizziness	28/74 (37.8%)
Dysgeusia	5/74 (6.8%)
Headache	28/74 (37.8%)
Hypoaesthesia	5/74 (6.8%)
Neuropathy peripheral	19/74 (25.7%)
Paraesthesia	5/74 (6.8%)
Peripheral sensory neuropathy	31/74 (41.9%)
Syncope	4/74 (5.4%)
Psychiatric disorders
Anxiety	4/74 (5.4%)
Depression	7/74 (9.5%)
Insomnia	13/74 (17.6%)
Renal and urinary disorders
Acute kidney injury	5/74 (6.8%)
Pollakiuria	6/74 (8.1%)
Proteinuria	5/74 (6.8%)
Urinary retention	4/74 (5.4%)
Respiratory, thoracic and mediastinal disorders
Cough	21/74 (28.4%)
Dyspnoea	29/74 (39.2%)
Dyspnoea exertional	4/74 (5.4%)
Epistaxis	5/74 (6.8%)
Nasal congestion	4/74 (5.4%)
Oropharyngeal pain	7/74 (9.5%)
Productive cough	4/74 (5.4%)
Sinus congestion	4/74 (5.4%)
Skin and subcutaneous tissue disorders
Alopecia	8/74 (10.8%)
Night sweats	10/74 (13.5%)
Petechiae	4/74 (5.4%)
Pruritus	10/74 (13.5%)
Rash	12/74 (16.2%)
Skin lesion	4/74 (5.4%)
Skin ulcer	4/74 (5.4%)
Surgical and medical procedures
Tooth extraction	5/74 (6.8%)
Vascular disorders
Flushing	8/74 (10.8%)
Haematoma	5/74 (6.8%)
Hypertension	14/74 (18.9%)
Hypotension	16/74 (21.6%)

Limitations/Caveats

Cohort 3 was discontinued and excluded from the safety and efficacy analyses. The survival analyses were subject to a high level of censoring.

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

Most restrictive: Site may not present or publish results of Trial without advance written notice of Sponsor or two years after completion of Trial at all participating sites. Site must submit all proposed publications or presentations to Sponsor for review. Sponsor can review communications prior to public release and embargo trial results communications for a period between 75 and 180 days from submission to Sponsor for review. Sponsor has right to request Site remove Confidential Information.