Trial Outcomes & Findings for Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other MDS/MPN, and Acute Myeloid Leukemia (NCT NCT02807272)

Last Updated: 2024-07-17

Results Overview

The ORR was estimated based on the number of participants who achieved an objective response (OR) (complete response \[CR\], complete cytogenetic remission \[CCR\], partial remission \[PR\], marrow response \[MR\], or clinical benefit \[CB\] performed by Principal Investigator according to the MDS/MPN International Working Group \[IWG\] criteria).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2024-07-17

Participant Flow

Participants affected by chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS)/myeloproliferative neoplasms (MPN) were recruited across 10 sites in the United States between January 2017 and November 2020.

Participants w/ CMML were grouped by KRAS/NRAS status (wild type \[WT\], mutation \[Mut\], missing) \& received tipifarnib 1200mg twice daily (BID) for 7 days, alternating weeks (Days 1-7, 15-21) in 28-day cycles. Following PA3 participants received tipifarnib 400mg orally w/ food, BID for 21 days in 28-day cycles. Those w/ MDS/MPN were stratified by ratio of expression (high/low) between CXCR4 \& CXCR2 (CXCR4/2 ratio) receptors to receive tipifarnib 400mg orally, BID on Day 1-21 of each 28-day cycle.

Participant milestones

Participant milestones
Measure	KRAS/NRAS WT Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Mut Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Missing Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	CXCR4/2 High Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	CXCR4/2 Low Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.
Overall Study STARTED	23	12	2	3	4
Overall Study COMPLETED	3	4	0	0	0
Overall Study NOT COMPLETED	20	8	2	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	KRAS/NRAS WT Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Mut Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Missing Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	CXCR4/2 High Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	CXCR4/2 Low Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.
Overall Study Death	9	5	2	0	1
Overall Study Lost to Follow-up	1	0	0	0	0
Overall Study Permanent Withdrawal of Consent	8	2	0	2	1
Overall Study Protocol-defined Disease Progression	0	1	0	0	1
Overall Study Study Terminated by Sponsor	1	0	0	1	0
Overall Study Other	1	0	0	0	1

Baseline Characteristics

Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other MDS/MPN, and Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	KRAS/NRAS WT n=23 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Mut n=12 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Missing n=2 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	CXCR4/2 High n=3 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	CXCR4/2 Low n=4 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	Total n=44 Participants Total of all reporting groups
Age, Continuous	70.0 years STANDARD_DEVIATION 6.62 • n=5 Participants	69.7 years STANDARD_DEVIATION 6.68 • n=7 Participants	76.0 years STANDARD_DEVIATION 2.83 • n=5 Participants	67.3 years STANDARD_DEVIATION 2.89 • n=4 Participants	70.5 years STANDARD_DEVIATION 4.04 • n=21 Participants	70.1 years STANDARD_DEVIATION 6.14 • n=8 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	19 Participants n=8 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	9 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	25 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	12 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	41 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=8 Participants
Race/Ethnicity, Customized White	20 Participants n=5 Participants	10 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	38 Participants n=8 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=8 Participants
Race/Ethnicity, Customized Native Hawaiian/other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: Per Protocol Analysis Set (PP Analysis Set): Included participants who received at least 1 dose of tipifarnib and had a baseline disease assessment and at least 1 postbaseline disease assessment.

Outcome measures

Outcome measures
Measure	KRAS/NRAS WT n=21 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Mut n=9 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Missing n=2 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	CXCR4/2 High n=1 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	CXCR4/2 Low n=3 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.
Objective Response Rate (ORR) MR	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Objective Response Rate (ORR) CR	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Objective Response Rate (ORR) CCR	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Objective Response Rate (ORR) PR	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Objective Response Rate (ORR) CB	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Objective Response Rate (ORR) ORR	3 Participants	3 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to approximately 15 months

Population: PP Analysis Set: Included participants who received at least 1 dose of tipifarnib and had a baseline disease assessment and at least 1 postbaseline disease assessment. Only participants who met the criteria for an OR and progressed or died were included in the analysis.

DoR was measured from the date the participant first met the criteria of an OR to the date that the participant progressed or until death from any cause during the period of disease assessments. Participants without progression or death were censored at the date of the last disease assessment. Participants who received subsequent anticancer therapy were censored at the date of last disease assessment before subsequent anticancer therapy. The median duration of response and corresponding 95% CI was estimated using the Kaplan Meier method.

Outcome measures

Outcome measures
Measure	KRAS/NRAS WT n=3 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Mut n=3 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Missing n=1 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	CXCR4/2 High Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	CXCR4/2 Low n=1 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.
Duration of Response (DoR)	14.6 months Interval 2.3 to Upper CI not calculable due to insufficient number of events.	NA months Interval 1.9 to Median and upper CI not calculable due to insufficient number of events.	4.7 months Upper and lower CI not calculable due to insufficient number of events.	—	NA months Median and CI not calculable due to insufficient number of events.

SECONDARY outcome

Timeframe: 1 year

Population: PP Analysis Set: Included participants who received at least 1 dose of tipifarnib and had a baseline disease assessment and at least 1 post-baseline disease assessment.

The PFS time was defined as the time from the date of consent signed to the date of documented disease progression or death due to any cause, whichever occurred first. Participants without progression or death were censored at the date of the last disease assessment. Participants who received subsequent anticancer therapy were censored at the date of the last disease assessment before subsequent anticancer therapy. The Kaplan-Meier product-limit method was used to estimate the 1-year PFS rate, as well as the corresponding 95% CI.

Outcome measures

Outcome measures
Measure	KRAS/NRAS WT n=21 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Mut n=9 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Missing n=2 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	CXCR4/2 High n=1 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	CXCR4/2 Low n=3 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.
Progression Free Survival (PFS)	9.2 months Interval 3.6 to 12.9	4.1 months Interval 2.1 to Upper CI not calculable due to insufficient number of events.	10.0 months Upper and lower CI not calculable due to insufficient number of events.	NA months Median and CI not calculable due to insufficient number of events.	11.0 months Interval 1.7 to Upper CI not calculable due to insufficient number of events.

SECONDARY outcome

Timeframe: Up to approximately 15 months

Population: PP Analysis Set: Included participants who received at least 1 dose of tipifarnib and had a baseline disease assessment and at least 1 post-baseline disease assessment.

OS time was defined as the time from the date of consent signed to the date of death due to any cause. Participants who were alive or lost to follow-up by the end of the study were censored at the date last known to be alive. The Kaplan-Meier method was used to estimate the proportion (%) of subjects without an event at 12 months, as well as their corresponding 95% CI.

Outcome measures

Outcome measures
Measure	KRAS/NRAS WT n=21 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Mut n=9 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Missing n=2 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	CXCR4/2 High n=1 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	CXCR4/2 Low n=3 Participants Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.
Overall Survival (OS)	14.4 months Interval 10.8 to Upper CI not calculable due to insufficient number of events.	NA months Interval 2.6 to Median and upper CI not calculable due to insufficient number of events.	10.6 months Interval 6.9 to Upper CI not calculable due to insufficient number of events.	NA months Median and CI not calculable due to insufficient number of events.	NA months Interval 11.0 to Median and upper CI not calculable due to insufficient number of events.

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in statistical analysis plan (SAP).

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with it. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE severity was rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03.: grade 1(mild), grade 2(moderate), grade 3(severe), grade 4(life-threatening), grade 5(death). An AE was considered serious if resulted in any of the following: death, life-threatening, caused inpatient hospitalization or prolonged it, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital abnormality/birth defect, or was an important medical event.

Outcome measures

Outcome measures
Measure	KRAS/NRAS WT n=37 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Mut n=7 Participants Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	KRAS/NRAS Missing Participants with CMML received tipifarnib at a starting dose of 1200 mg, BID, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles.	CXCR4/2 High Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.	CXCR4/2 Low Participants with MDS/MPN received tipifarnib at a starting dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) Any TEAE	37 Participants	7 Participants	—	—	—
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) Any tipifarnib-related TEAE	37 Participants	6 Participants	—	—	—
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) Any serious TEAE	23 Participants	1 Participants	—	—	—
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) Any tipifarnib-related serious TEAE	13 Participants	1 Participants	—	—	—

Adverse Events

CMML

Serious events: 23 serious events

Other events: 37 other events

Deaths: 17 deaths

MDS/MPS

Serious events: 1 serious events

Other events: 7 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Operations

Kura Oncology Inc.

Phone: +1 617 588-3755

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee There are agreements in place between clinical trial sites and the Sponsor (or its agents) that govern discussion or publication of trial results by the sites or their employees after the trial is completed.
Publication restrictions are in place

Restriction type: OTHER

Measure	CMML n=37 participants at risk Participants with CMML were grouped by KRAS/NRAS mutational status (wild type \[WT\], mutation \[Mut\], missing) and given tipifarnib 1200mg twice daily (BID) for 7 days in alternating weeks (Days 1-7, 15-21) in 28-day cycles.	MDS/MPS n=7 participants at risk Participants with MDS/MPN were stratified by ratio of expression (high or low) between CXCR4 and CXCR2 (CXCR4/2 ratio) receptors to receive tipifarnib at a dose of 400 mg, orally, BID on Day 1 through 21 of each 28-day treatment cycle.
Blood and lymphatic system disorders Febrile neutropenia	10.8% 4/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	14.3% 1/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Blood and lymphatic system disorders Anaemia	5.4% 2/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Cardiac disorders Atrial fibrillation	5.4% 2/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Cardiac disorders Cardiac arrest	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Cardiac disorders Cardiac failure	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Cardiac disorders Cardiac failure congestive	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Cardiac disorders Myocardial infarction	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Gastrointestinal disorders Gastric haemorrhage	5.4% 2/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Gastrointestinal disorders Dental caries	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Gastrointestinal disorders Duodenal ulcer	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Gastrointestinal disorders Gastritis	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Gastrointestinal disorders Nausea	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
General disorders Multiple organ dysfunction syndrome	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
General disorders Non-cardiac chest pain	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
General disorders Pyrexia	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Hepatobiliary disorders Hepatitis acute	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Infections and infestations Pneumonia	5.4% 2/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Infections and infestations Lung infection	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Infections and infestations Pneumonia viral	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Infections and infestations Scrotal infection	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Infections and infestations Sepsis	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Infections and infestations Skin infection	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Injury, poisoning and procedural complications Contusion	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Injury, poisoning and procedural complications Fall	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Injury, poisoning and procedural complications Subdural haematoma	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Investigations Platelet count decreased	8.1% 3/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Metabolism and nutrition disorders Tumour lysis syndrome	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Musculoskeletal and connective tissue disorders Muscular weakness	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Nervous system disorders Syncope	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Psychiatric disorders Delirium	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 1/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.
Renal and urinary disorders Acute kidney injury	8.1% 3/37 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.	0.00% 0/7 • Up to approximately 3 years FAS: All enrolled participants who received at least one dose of tipifarnib. Data was pooled into CMML and MDS/MPN arms as pre-specified in SAP.