Trial Outcomes & Findings for Study of Baricitinib, a JAK1/2 Inhibitor, in Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation (NCT NCT02759731)

Last Updated: 2024-10-08

Results Overview

DLT is defined as any grade ≥3 non-hematologic or grade ≥4 hematologic adverse event, or hemoglobin \<6.5 g/dL, within 4 weeks of starting any dose level (1mg, 2mg, or 4 mg) except those that are clearly and incontrovertibly due to extraneous causes. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Starting at each dose level initiation, every 2 weeks up to the first 4 weeks of each dose

Results posted on

2024-10-08

Participant Flow

This is a single arm study (with intra-patient dose escalation) - so all participants are exposed to both dose levels unless they prematurely developed toxicity that led to study discontinuation or dose modification. We report as one arm and then report the dose modifications/discontinuation separately - but the modification/discontinuation does not define those participants as a separate group.

Participant milestones

Participant milestones
Measure	Dose Level 1, 2 mg of Baricitinib -> Dose Level 2, 4 mg of Baricitinib Dose Level 1, 2 mg of Baricitinib -\> Dose Level 2, 4 mg of Baricitinib
Overall Study STARTED	24
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level 1, 2 mg of Baricitinib -> Dose Level 2, 4 mg of Baricitinib Dose Level 1, 2 mg of Baricitinib -\> Dose Level 2, 4 mg of Baricitinib
Overall Study Did not complete treatment.	8

Baseline Characteristics

Study of Baricitinib, a JAK1/2 Inhibitor, in Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1, 2 mg of Baricitinib -> Dose Level 2, 4 mg of Baricitinib n=24 Participants Dose Level 1, 2 mg of Baricitinib -\> Dose Level 2, 4 mg of Baricitinib
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age, Continuous	50.7 years STANDARD_DEVIATION 12.27 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Starting at each dose level initiation, every 2 weeks up to the first 4 weeks of each dose

Population: Single arm study (intra-patient(pt) dose escalation). All pts exposed to both dose levels(DL) unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. Modification/discontinuation does not define those pts as a separate group. 20/24pts analyzed DL2 because they never made it to 3month mark when dose escalation occurred/never underwent dose escalation to 4mg due to toxicity/progression.

Outcome measures

Outcome measures
Measure	Dose Level 1, 2 mg of Baricitinib n=24 Participants Dose Level 1, 2 mg of Baricitinib	Dose Level 2, 4 mg of Baricitinib n=20 Participants Dose Level 2, 4 mg of Baricitinib
Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: every 4 weeks through study completion (up to 48 weeks)

Population: This is a single arm study (with intra-patient dose escalation) - so all participants are exposed to both dose levels unless they prematurely developed toxicity that led to study discontinuation or dose modification. We report as one arm and then report the dose modifications/discontinuation separately - but the modification/discontinuation does not define those participants as a separate group.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.

Outcome measures

Outcome measures
Measure	Dose Level 1, 2 mg of Baricitinib n=24 Participants Dose Level 1, 2 mg of Baricitinib	Dose Level 2, 4 mg of Baricitinib Dose Level 2, 4 mg of Baricitinib
Phase 2: Number of Participants With Any Serious and/or Non-Serious Grades 3, 4, and/or 5 Adverse Events Due to Drug Grade 3	2 Participants	—
Phase 2: Number of Participants With Any Serious and/or Non-Serious Grades 3, 4, and/or 5 Adverse Events Due to Drug Grade 4	0 Participants	—
Phase 2: Number of Participants With Any Serious and/or Non-Serious Grades 3, 4, and/or 5 Adverse Events Due to Drug Grade 5	0 Participants	—

PRIMARY outcome

Timeframe: 24 weeks

Response was assessed by the National Institutes of Health (NIH) chronic graft-versus-host disease (cGVHD) response criteria. Complete Response (CR) is defined as resolution of all manifestations in each organ or site. Partial Response (PR) is defined as improvement at least 1 organ or site without progression in any other organ or site. Lack of Response including unchanged, mixed response, and disease progression. Mixed response is a CR or PR in at least 1 organ accompanied by progression in another organ. Unchanged is outcomes that do not meet the criteria for CR, PR, disease progression, or mixed response. Disease Progression is a change in the manifestations in each organ or site that does not meet the criteria for CR, PR, mixed response, unchanged or lack of response.

Outcome measures

Outcome measures
Measure	Dose Level 1, 2 mg of Baricitinib n=24 Participants Dose Level 1, 2 mg of Baricitinib	Dose Level 2, 4 mg of Baricitinib Dose Level 2, 4 mg of Baricitinib
Phase 2: Overall Response at 24 Weeks Complete Response	0 Participants	—
Phase 2: Overall Response at 24 Weeks Disease Progression	0 Participants	—
Phase 2: Overall Response at 24 Weeks Not Evaluable: participants did not make it to the 24-week mark for response assessment.	5 Participants	—
Phase 2: Overall Response at 24 Weeks Partial Response	16 Participants	—
Phase 2: Overall Response at 24 Weeks Mixed Response	3 Participants	—
Phase 2: Overall Response at 24 Weeks Unchanged	0 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Dose Level 1, 2 mg of Baricitinib n=24 Participants Dose Level 1, 2 mg of Baricitinib	Dose Level 2, 4 mg of Baricitinib Dose Level 2, 4 mg of Baricitinib
Phase 1 and 2: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	21 Participants	—

Adverse Events

Dose Level 1, 2 mg of Baricitinib -> Dose Level 2, 4 mg of Baricitinib

Serious events: 8 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1, 2 mg of Baricitinib -> Dose Level 2, 4 mg of Baricitinib n=24 participants at risk Dose Level 1, 2 mg of Baricitinib -\> Dose Level 2, 4 mg of Baricitinib
Immune system disorders Anaphylaxis	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, Post transplant lymphoproliferative disorder	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Joint infection	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Lung infection	12.5% 3/24 • Number of events 3 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Musculoskeletal and connective tissue disorders Myalgia	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, squamous cell carcinoma	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Nervous system disorders Presyncope	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Skin infection	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Tooth infection	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Upper respiratory infection	8.3% 2/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Bone infection	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.

Other adverse events

Other adverse events
Measure	Dose Level 1, 2 mg of Baricitinib -> Dose Level 2, 4 mg of Baricitinib n=24 participants at risk Dose Level 1, 2 mg of Baricitinib -\> Dose Level 2, 4 mg of Baricitinib
Gastrointestinal disorders Abdominal pain	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Alanine aminotransferase increased	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Alkaline phosphatase increased	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Immune system disorders Allergic reaction	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Blood and lymphatic system disorders Anemia	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Musculoskeletal and connective tissue disorders Back pain	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Gastrointestinal disorders Bloating	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, Lymphadenopathy (CT)	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Carbon monoxide diffusing capacity decreased	12.5% 3/24 • Number of events 3 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Eye disorders Cataract	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Cholesterol high	8.3% 2/24 • Number of events 3 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Eye disorders Conjunctivitis	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Gastrointestinal disorders Constipation	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 2/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Creatinine increased	12.5% 3/24 • Number of events 4 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Metabolism and nutrition disorders Dehydration	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Gastrointestinal disorders Diarrhea	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Enterocolitis infectious	8.3% 2/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Eye disorders Eye disorders - Other, Chalazion RUL	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Eye infection	4.2% 1/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Eye disorders Eye pain	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Injury, poisoning and procedural complications Fall	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
General disorders Fatigue	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
General disorders Fever	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Musculoskeletal and connective tissue disorders Flank pain	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Forced expiratory volume decreased	12.5% 3/24 • Number of events 4 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Gastrointestinal disorders Gastritis	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Nervous system disorders Headache	8.3% 2/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Metabolism and nutrition disorders Hyperkalemia	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Vascular disorders Hypertension	12.5% 3/24 • Number of events 4 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Metabolism and nutrition disorders Hypertriglyceridemia	12.5% 3/24 • Number of events 3 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Metabolism and nutrition disorders Hypoalbuminemia	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Metabolism and nutrition disorders Hypoglycemia	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Metabolism and nutrition disorders Hypokalemia	16.7% 4/24 • Number of events 7 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Metabolism and nutrition disorders Hypophosphatemia	20.8% 5/24 • Number of events 8 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Vascular disorders Hypotension	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Gastrointestinal disorders Ileus	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Infections and infestations - Other, Sputum culture + for Pseudomonas a.	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Infections and infestations - Other, Thrush	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Infections and infestations - Other, scabies	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
General disorders Injection site reaction	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, Right peroneus brevis tendon tear	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, srt. wrist sprain	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Psychiatric disorders Insomnia	8.3% 2/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Lung infection	12.5% 3/24 • Number of events 4 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Lymphocyte count decreased	8.3% 2/24 • Number of events 4 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, metabolic acidosis	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Mucosal infection	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, muscle spasms, pain and stiffness upper arm	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Musculoskeletal and connective tissue disorders Myalgia	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Gastrointestinal disorders Nausea	12.5% 3/24 • Number of events 3 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Neutrophil count decreased	8.3% 2/24 • Number of events 6 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Ear and labyrinth disorders Otitis externa	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Ear and labyrinth disorders Otitis media	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Musculoskeletal and connective tissue disorders Pain in extremity	12.5% 3/24 • Number of events 3 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Nervous system disorders Peripheral sensory neuropathy	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Eye disorders Photophobia	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Nervous system disorders Presyncope	8.3% 2/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Skin and subcutaneous tissue disorders Pruritus	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Skin and subcutaneous tissue disorders Rash maculo-papular	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Sinusitis	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, Oral pyogenic granuloma	4.2% 1/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Skin infection	8.3% 2/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Injury, poisoning and procedural complications Spinal fracture	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Vascular disorders Thromboembolic event	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Upper respiratory infection	33.3% 8/24 • Number of events 14 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Gastrointestinal disorders Vomiting	4.2% 1/24 • Number of events 2 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Investigations Weight gain	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Nervous system disorders Syncope	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.
Infections and infestations Vaginal infection	4.2% 1/24 • Number of events 1 • Date treatment consent signed to 30 days off study drug, approximately 73 months and 28 days. Single arm study (intra-patient (pt) dose escalation). All pts is exposed to both dose levels unless prematurely developed toxicity that led to study discontinuation/dose modification. We report as 1 arm\&then report dose modifications/discontinuation separately. The modification/discontinuation does not define those pts as a separate group. We cannot report adverse events(AEs) per dose level as some late AEs are considered cumulative from exposure to drug which was interchangeable and increased.

Additional Information

Dr. Steven Pavletic

National Cancer Institute

Phone: 240-760-6174

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place