Trial Outcomes & Findings for Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery (NCT NCT02775851)

Last Updated: 2025-12-02

Results Overview

Pathologic complete response is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standard of care.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2025-12-02

Participant Flow

57 participants were enrolled, but one participant from Cohort A withdrew consent prior to receiving protocol treatment and is not analyzable.

Participant milestones

Participant milestones
Measure	Cohort A: Resectable - Pembrolizumab, Surgery Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Overall Study STARTED	30	27
Overall Study COMPLETED	28	5
Overall Study NOT COMPLETED	2	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Resectable - Pembrolizumab, Surgery Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Overall Study Adverse Event	1	10
Overall Study Refusal Unrelated to Adverse Event	0	1
Overall Study Progression/Relapse	0	4
Overall Study Other - Not Protocol Specified	0	7
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Resectable - Pembrolizumab, Surgery n=29 Participants Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab n=27 Participants Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.	Total n=56 Participants Total of all reporting groups
Age, Customized Age	74.7 years n=121 Participants	75.2 years n=122 Participants	74.9 years n=243 Participants
Sex: Female, Male Female	7 Participants n=121 Participants	2 Participants n=122 Participants	9 Participants n=243 Participants
Sex: Female, Male Male	22 Participants n=121 Participants	25 Participants n=122 Participants	47 Participants n=243 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=121 Participants	0 Participants n=122 Participants	1 Participants n=243 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=121 Participants	26 Participants n=122 Participants	52 Participants n=243 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=121 Participants	1 Participants n=122 Participants	3 Participants n=243 Participants
Race/Ethnicity, Customized Race · White	28 Participants n=121 Participants	27 Participants n=122 Participants	55 Participants n=243 Participants
Race/Ethnicity, Customized Race · Unknown	1 Participants n=121 Participants	0 Participants n=122 Participants	1 Participants n=243 Participants
Performance Status 0	22 Participants n=121 Participants	19 Participants n=122 Participants	41 Participants n=243 Participants
Performance Status 1	7 Participants n=121 Participants	8 Participants n=122 Participants	15 Participants n=243 Participants
T Stage Tis	0 Participants n=121 Participants	1 Participants n=122 Participants	1 Participants n=243 Participants
T Stage T0	0 Participants n=121 Participants	2 Participants n=122 Participants	2 Participants n=243 Participants
T Stage T1a	1 Participants n=121 Participants	1 Participants n=122 Participants	2 Participants n=243 Participants
T Stage T1b	2 Participants n=121 Participants	0 Participants n=122 Participants	2 Participants n=243 Participants
T Stage T2a	6 Participants n=121 Participants	1 Participants n=122 Participants	7 Participants n=243 Participants
T Stage T2b	1 Participants n=121 Participants	1 Participants n=122 Participants	2 Participants n=243 Participants
T Stage T3a	7 Participants n=121 Participants	4 Participants n=122 Participants	11 Participants n=243 Participants
T Stage T3b	1 Participants n=121 Participants	2 Participants n=122 Participants	3 Participants n=243 Participants
T Stage T4a	8 Participants n=121 Participants	8 Participants n=122 Participants	16 Participants n=243 Participants
T Stage T4b	2 Participants n=121 Participants	5 Participants n=122 Participants	7 Participants n=243 Participants
T Stage Tx	1 Participants n=121 Participants	0 Participants n=122 Participants	1 Participants n=243 Participants
T Stage Unknown	0 Participants n=121 Participants	2 Participants n=122 Participants	2 Participants n=243 Participants
N Stage N0	24 Participants n=121 Participants	12 Participants n=122 Participants	36 Participants n=243 Participants
N Stage N1b	2 Participants n=121 Participants	2 Participants n=122 Participants	4 Participants n=243 Participants
N Stage N2a	0 Participants n=121 Participants	1 Participants n=122 Participants	1 Participants n=243 Participants
N Stage N2b	0 Participants n=121 Participants	2 Participants n=122 Participants	2 Participants n=243 Participants
N Stage N2c	3 Participants n=121 Participants	1 Participants n=122 Participants	4 Participants n=243 Participants
N Stage N3	0 Participants n=121 Participants	2 Participants n=122 Participants	2 Participants n=243 Participants
N Stage NX	0 Participants n=121 Participants	4 Participants n=122 Participants	4 Participants n=243 Participants
N Stage Unknown	0 Participants n=121 Participants	3 Participants n=122 Participants	3 Participants n=243 Participants
M Stage M0	29 Participants n=121 Participants	8 Participants n=122 Participants	37 Participants n=243 Participants
M Stage M1a	0 Participants n=121 Participants	1 Participants n=122 Participants	1 Participants n=243 Participants
M Stage M1b	0 Participants n=121 Participants	11 Participants n=122 Participants	11 Participants n=243 Participants
M Stage M1c	0 Participants n=121 Participants	7 Participants n=122 Participants	7 Participants n=243 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Pathologic complete response is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standard of care.

Outcome measures

Outcome measures
Measure	Cohort A: Resectable - Pembrolizumab, Surgery n=29 Participants Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Pathologic Complete Response (pCR) Rate (Cohort A)	55 percentage of participants Interval 36.0 to 74.0	—

PRIMARY outcome

Timeframe: Up to 5 years

Population: All eligible and analyzable participants with measurable disease at baseline (n=27).

Complete response (per RECIST 1.1) defined as: disappearance of all target and non-target lesions no new lesions, no disease related symptoms, and any lymph nodes must have reduction in short axis to \< 1.0 cm.

Outcome measures

Outcome measures
Measure	Cohort A: Resectable - Pembrolizumab, Surgery n=27 Participants Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Complete Response (CR) Rate (Cohort B)	37 percentage of participants Interval 19.0 to 58.0	—

SECONDARY outcome

Timeframe: Up to 3 months

Population: All eligible and analyzable participants with measurable disease at baseline (n=26).

Unconfirmed complete (CR) and partial responses (PR) at end of neoadjuvant treatment assessment among patients with measurable disease. CR and PR per response evaluation criteria in solid tumors (RECIST v1.1): CR is complete disappearance of all target and non-target lesions, no new lesions, no disease related symptoms, and lymph nodes must have reduction in short axis to \<1.0cm. PR is greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Overall response = CR + PR.

Outcome measures

Outcome measures
Measure	Cohort A: Resectable - Pembrolizumab, Surgery n=26 Participants Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
9 Week Response Rate (Cohort A)	46 percentage of participants Interval 27.0 to 67.0	—

SECONDARY outcome

Timeframe: Up to 5 years

From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Outcome measures

Outcome measures
Measure	Cohort A: Resectable - Pembrolizumab, Surgery n=29 Participants Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab n=27 Participants Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Overall Survival (Cohort A and B)	NA months Interval 37.0 to There was insufficient follow-up data to estimate.	50.6 months Interval 42.4 to There was insufficient follow-up data to estimate.

SECONDARY outcome

Timeframe: Up to 5 years

From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm, unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided), appearance of any new lesion/site, or death due to disease without prior documentation of progression and without symptomatic deterioration

Outcome measures

Outcome measures
Measure	Cohort A: Resectable - Pembrolizumab, Surgery n=27 Participants Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Progression Free Survival (Cohort B)	49.2 months Interval 33.3 to There was insufficient follow-up data to estimate.	—

SECONDARY outcome

Timeframe: Duration of treatment and follow-up until death or 5 years post registration.

Population: Participants who were eligible and received at least one dose of protocol treatment. 29 participants were evaluable or AEs in Cohort A and 27 were evaluable or AEs in Cohort B.

Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 4.0 was used for all AE reporting.

Outcome measures

Outcome measures
Measure	Cohort A: Resectable - Pembrolizumab, Surgery n=29 Participants Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: Unresectable - Pembrolizumab n=27 Participants Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pancreatitis	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Rash maculo-papular	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lung infection	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Mucositis oral	1 Participants	0 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Musculoskeletal and connective tiss disorder - Other	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Myositis	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Sepsis	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Skin and subcutaneous tissue disorders - Other	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Upper gastrointestinal hemorrhage	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lipase increased	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Abdominal pain	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Adrenal insufficiency	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Back pain	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs CPK increased	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Colitis	1 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Diarrhea	0 Participants	2 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dyspnea	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypokalemia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypoxia	0 Participants	1 Participants
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Immune system disorders - Other, specify	0 Participants	1 Participants

Adverse Events

Cohort A: MK-3475 (Pembrolizumab)

Serious events: 1 serious events

Other events: 23 other events

Deaths: 5 deaths

Cohort B: MK-3475 (Pembrolizumab)

Serious events: 14 serious events

Other events: 25 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

Melanoma Committee Statistician

SWOG Statistics and Data Management Center

Phone: 2066674623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Cohort A: MK-3475 (Pembrolizumab) n=29 participants at risk Resectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.	Cohort B: MK-3475 (Pembrolizumab) n=27 participants at risk Unresectable patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.
Blood and lymphatic system disorders Anemia	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Cardiac disorders Atrial fibrillation	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Cardiac disorders Heart failure	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Endocrine disorders Adrenal insufficiency	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	7.4% 2/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Gastrointestinal disorders Abdominal pain	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Gastrointestinal disorders Colitis	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	7.4% 2/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Gastrointestinal disorders Colonic hemorrhage	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Gastrointestinal disorders Diarrhea	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	7.4% 2/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Gastrointestinal disorders Gastrointestinal disorders-Other	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Gastrointestinal disorders Pancreatitis	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	7.4% 2/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
General disorders Fever	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Immune system disorders Immune system disorders-Other	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Infections and infestations Lung infection	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	7.4% 2/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Infections and infestations Sepsis	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Injury, poisoning and procedural complications Fall	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Investigations CPK increased	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Investigations Cardiac troponin I increased	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tiss disorder - Other	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Renal and urinary disorders Renal and urinary disorders-Other	3.4% 1/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	0.00% 0/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	11.1% 3/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Vascular disorders Hypertension	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.
Vascular disorders Hypotension	0.00% 0/29 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.	3.7% 1/27 • Duration of treatment and follow up until death or 5 years post registration. CTCAE version 4.0 was used for toxicity SAEs reporting. There were 29 participants in Cohort A that were assessed for AEs and 27 participants Cohort B that were assessed for AEs.