A Study Evaluating the Efficacy and the Safety of First-line Chemotherapy Combined With the Therapeutic Vaccine Named TG4010 and Nivolumab in Patients With Advanced Non-squamous Non-Small Cell Lung Cancer (NSCLC)

• Sponsor: Transgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03353675
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 44
• Locations: 9
• Arm: 1
• Actual Duration (Months): 37.4
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter, single arm, open label phase II study in treatment-naïve for advanced stage of the disease and immunotherapy-naïve patients with advanced non-squamous NSCLC and with < 50% of tumor cells expressing programmed death-ligand 1 (PD-L1) by immunohistochemical (IHC) staining.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Metastatic	Biological: TG4010; Drug: Chemotherapy; Drug: Nivolumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Evaluating the Efficacy and the Safety of First-line Chemotherapy Combined With TG4010 and Nivolumab in Patients With Advanced Non-squamous Non-Small Cell Lung Cancer (NSCLC)
• Actual Study Start Date: Jan 5, 2018
• Actual Primary Completion Date: Nov 20, 2019
• Actual Study Completion Date: Feb 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TG4010/Chemotherapy/Nivolumab	Biological: TG4010; 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks; Drug: Chemotherapy; Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance; Drug: Nivolumab; 360 mg IV administration every 3 weeks

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [15 months]

   Percentage of participants whose best overall response is complete response or partial response using RECIST 1.1. confirmed by a second scan no less than 4 weeks after the criteria for response are first met. Complete response: disappearance of all lesions and no new lesions. Partial response: decrease of at least 30% in the sum of the diameters of measurable lesions taking as reference the baseline sum of diameters, no progression of non-measurable lesions and no new lesions.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [28 months]

   Time from the date of the first study drug administration to the date of first documented tumor progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The Kaplan-Meier estimator was used to estimate median PFS and its confidence interval.

2. Disease Control Rate (DCR) [15 months]

   Percentage of participants whose best overall response is either complete response, partial response or stable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI: Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions and no measurable non-target lesions; Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD).

3. Overall Survival [28 months]

   Overall Survival (OS) is defined as the time from the first study drug administration to the date of death due to any cause. The Kaplan-Meier estimator was used to estimate median OS and its confidence interval.

4. Duration of Overall Response (DoR) [28 months]

   Time from first documented response (complete response or partial response) until documented disease progression or death due to lung cancer.

5. Number of Participants With Adverse Events or Abnormalities [28 months]

   The assessment of safety of the combination was based mainly on the frequency of adverse events, serious adverse events, adverse events of special interest (Injection site reaction, fatigue, pyrexia, infusion-related reactions and diarrhea), immune-mediated adverse events and laboratories abnormalities.

Eligibility Criteria

Criteria

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

Principal Inclusion Criteria:

• Female or male patients age > 18 years-old

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 at study entry

• Life expectancy of at least 3 months

• Histologically confirmed non-squamous NSCLC (adenocarcinoma, large cell carcinoma, undifferentiated carcinoma or other)

• Stage IIIB-IV cancer or delayed relapse of any stage not amenable to surgery or radiotherapy with curative intent.

• PD-L1 expression by immunohistochemistry in < 50% of tumor cells

• Patients must be chemotherapy-naïve for the advanced stage of the disease. Previous neoadjuvant and/or adjuvant chemotherapy is allowed for patients who successfully underwent complete radical surgery and if last treatment was administered more than 12 months prior to the start of the study treatment.

• At least one measurable lesion by CT scan based on RECIST 1.1 performed within 28 days prior to start of study treatment

• Adequate hematological, hepatic, and renal functions

• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study drug

• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug plus 30 days for a total of 5 months posttreatment completion. Highly effective contraception are defined in the protocol.

• Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 90 days for a total of 7 months post-treatment completion

Principal Exclusion Criteria:

• Patients having central nervous system (CNS) metastases

• Patients with pericardial effusion

• Prior exposure to cancer immunotherapy including cancer vaccines, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-Lymphocyte antigen- 4 antibody or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways

• Patients with epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK)- rearrangements leading to eligibility for tyrosine kinase inhibitor (TKI) treatment (tests mandatory)

• Prior history of other malignancy except basal cell carcinoma of the skin, cervical intra epithelial neoplasia, and other cancer curatively treated with no evidence of disease for at least 3 years

• Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment

• Patients with an active, known or suspected autoimmune disease

• Patient with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity

• Patients with grade ≥ 2 neuropathy

• Signs or symptoms of infection within 14 days prior to start of study treatment or active infection requiring systemic therapy

• Positive serology for HIV or hepatitis C virus (HCV); presence in the serum of the antigens hepatitis B (HBs) at baseline

• Patient with any underlying medical condition that the treating physician considers might be aggravated by treatment or which is not controlled (e.g., elevated troponin or creatinine, uncontrolled diabetes)

• History of cardiovascular conditions within 12 months of enrollment

• Left ventricular ejection fraction less than the Lower Limit of Normal as assessed by echocardiography (or multigated acquisition (MUGA) scan)

• Patient with major surgery or radiotherapy within 3 weeks prior to the start of the study treatment. However, prior surgery or radiation therapy aimed at local palliation or attempted local disease control (except in case of thoracic radiotherapy) is permitted but has to be completed 2 weeks before treatment start

• Pregnant or nursing (lactating) women

• Patients with an organ allograft

• Any known allergy to eggs, gentamicin or history of allergy or hypersensitivity to study drug components

• Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatments

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charlotte	Charlotte	North Carolina	United States	28204
2	Nashville	Nashville	Tennessee	United States	37203
3	Libramont	Libramont		Belgium
4	Créteil	Créteil		France
5	Mulhouse	Mulhouse		France
6	Rennes	Rennes		France
7	Strasbourg	Strasbourg		France
8	Budapest	Budapest		Hungary
9	Szekesfehervar	Szekesfehervar		Hungary

Sponsors and Collaborators

• Transgene
• Bristol-Myers Squibb

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 13, 2018
• Statistical Analysis Plan - Nov 13, 2019

More Information

Publications

None provided.

• Responsible Party: Transgene
• ClinicalTrials.gov Identifier: NCT03353675
• Other Study ID Numbers: TG4010.24
• First Posted: Nov 27, 2017
• Last Update Posted: Jan 11, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Transgene: Metastatic NSCLC; Advanced lung malignancy
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Nivolumab

Study Results

Participant Flow

Recruitment Details	The study was conducted at 2 study sites in United States, 4 sites in France, 2 sites in Hungary and 1 site in Belgium.
Pre-assignment Detail	A total of 44 participants were enrolled and treated with at least one administration of each study drug.

Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
Period Title: Overall Study
STARTED	44
COMPLETED	40
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
Overall Participants	44
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 63.6%
>=65 years	16 36.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.7 (8.64)
Sex: Female, Male (Count of Participants)
Female	17 38.6%
Male	27 61.4%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
Belgium	6 13.6%
Hungary	6 13.6%
United States	6 13.6%
France	26 59.1%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (participants) [Number]
ECOG PS 0	21 47.7%
ECOG PS 1	23 52.3%
Body Mass Index (BMI) (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	24.4
PD-L1 percentage of stained cells (Count of Participants)
<1	22 50%
1 - <50	22 50%
≥50	0 0%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	Percentage of participants whose best overall response is complete response or partial response using RECIST 1.1. confirmed by a second scan no less than 4 weeks after the criteria for response are first met. Complete response: disappearance of all lesions and no new lesions. Partial response: decrease of at least 30% in the sum of the diameters of measurable lesions taking as reference the baseline sum of diameters, no progression of non-measurable lesions and no new lesions.
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

The Evaluable Patient's Population is the primary population for efficacy analyses. Evaluable Patient's Population consists of all participants without major protocol deviation and have at least one baseline and one post-baseline evaluable CT-scan after study treatment start except early disease progression and death due to lung cancer.

Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
Measure Participants	40
Number (90% Confidence Interval) [percentage of participants]	32.5 73.9%

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Time from the date of the first study drug administration to the date of first documented tumor progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The Kaplan-Meier estimator was used to estimate median PFS and its confidence interval.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

The Evaluable Patient's Population is the primary population for efficacy analyses. Evaluable Patient's Population consists of all participants without major protocol deviation and have at least one baseline and one post-baseline evaluable CT-scan after study treatment start except early disease progression and death due to lung cancer.

Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
Measure Participants	40
Median (Inter-Quartile Range) [Months]	5.7

3. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Percentage of participants whose best overall response is either complete response, partial response or stable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI: Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions and no measurable non-target lesions; Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD).
Time Frame	15 months

Outcome Measure Data

Analysis Population Description

The Evaluable Patient's Population is the primary population for efficacy analyses. Evaluable Patient's Population consists of all participants without major protocol deviation and have at least one baseline and one post-baseline evaluable CT-scan after study treatment start except early disease progression and death due to lung cancer.

Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
Measure Participants	40
Number (90% Confidence Interval) [percentage of participants]	75.0 170.5%

4. Secondary Outcome

Title	Overall Survival
Description	Overall Survival (OS) is defined as the time from the first study drug administration to the date of death due to any cause. The Kaplan-Meier estimator was used to estimate median OS and its confidence interval.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

The Evaluable Patient's Population is the primary population for efficacy analyses. Evaluable Patient's Population consists of all participants without major protocol deviation and have at least one baseline and one post-baseline evaluable CT-scan after study treatment start except early disease progression and death due to lung cancer.

Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
Measure Participants	40
Median (95% Confidence Interval) [Months]	14.9

5. Secondary Outcome

Title	Duration of Overall Response (DoR)
Description	Time from first documented response (complete response or partial response) until documented disease progression or death due to lung cancer.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Responders: all evaluable participants with complete response or partial response. The start date was the date of first documented response (complete response or partial response) and the end date was the date of first documented disease progression. If no progression has been observed at the cut-off date of analysis or at the date when a subsequent cancer therapy was started, duration of response was censored at the date of the last evaluable tumor assessment.

Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
Measure Participants	13
Median (Inter-Quartile Range) [Weeks]	74.9

6. Secondary Outcome

Title	Number of Participants With Adverse Events or Abnormalities
Description	The assessment of safety of the combination was based mainly on the frequency of adverse events, serious adverse events, adverse events of special interest (Injection site reaction, fatigue, pyrexia, infusion-related reactions and diarrhea), immune-mediated adverse events and laboratories abnormalities.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

Safety population (all treated participants)

Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
Measure Participants	44
Adverse events	44 100%
Serious adverse events	28 63.6%
Adverse events of special interest	37 84.1%
Immune-mediated adverse events	14 31.8%
Grade 3/4 laboratories abnormalities	31 70.5%

Adverse Events

Time Frame	Collection of adverse events / serious adverse events starts from the date of signature of the informed consent form up to the safety follow-up visits (100 days after the last administration of any study treatment administration). Timeframe was approximately 28 months.
Arm/Group Title	TG4010/Chemotherapy/Nivolumab
Arm/Group Description	TG4010: 1 dose (1x1E+08) Subcutaneous injection/week over 6 weeks then 1 dose/3 weeks Chemotherapy: Pemetrexed/Cisplatin or Carboplatin Pemetrexed maintenance Nivolumab: 360 mg IV administration every 3 weeks
All Cause Mortality
	TG4010/Chemotherapy/Nivolumab
	Affected / at Risk (%)	# Events
Total	28/44 (63.6%)
Serious Adverse Events
	TG4010/Chemotherapy/Nivolumab
	Affected / at Risk (%)	# Events
Total	28/44 (63.6%)
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA	2/44 (4.5%)	2
THROMBOCYTOPENIA	1/44 (2.3%)	1
Gastrointestinal disorders
VOMITING	3/44 (6.8%)	3
ABDOMINAL PAIN	1/44 (2.3%)	1
AUTOIMMUNE COLITIS	1/44 (2.3%)	1
COLITIS ULCERATIVE	1/44 (2.3%)	1
DIARRHOEA	1/44 (2.3%)	1
DUODENITIS	1/44 (2.3%)	1
PANCREATITIS	1/44 (2.3%)	1
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION	9/44 (20.5%)	9
FATIGUE	2/44 (4.5%)	2
CONDITION AGGRAVATED	1/44 (2.3%)	1
Hepatobiliary disorders
CHOLANGITIS ACUTE	1/44 (2.3%)	1
Immune system disorders
ANAPHYLACTIC REACTION	1/44 (2.3%)	1
Infections and infestations
PNEUMONIA	2/44 (4.5%)	2
BARTHOLINITIS	1/44 (2.3%)	1
BRAIN ABSCESS	1/44 (2.3%)	1
CELLULITIS	1/44 (2.3%)	1
DIVERTICULITIS	1/44 (2.3%)	1
FEBRILE INFECTION	1/44 (2.3%)	1
SEPTIC SHOCK	1/44 (2.3%)	1
Investigations
BLOOD CREATININE INCREASED	1/44 (2.3%)	1
Metabolism and nutrition disorders
DEHYDRATION	1/44 (2.3%)	1
HYPERCALCAEMIA	1/44 (2.3%)	1
HYPERGLYCAEMIA	1/44 (2.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN	1/44 (2.3%)	1
Nervous system disorders
CEREBRAL INFARCTION	1/44 (2.3%)	1
CEREBRAL ISCHAEMIA	1/44 (2.3%)	1
HEADACHE	1/44 (2.3%)	1
ISCHAEMIC STROKE	1/44 (2.3%)	1
LOSS OF CONSCIOUSNESS	1/44 (2.3%)	1
NEUROPATHY PERIPHERAL	1/44 (2.3%)	1
TRANSIENT ISCHAEMIC ATTACK	1/44 (2.3%)	1
Renal and urinary disorders
ACUTE KIDNEY INJURY	1/44 (2.3%)	1
Reproductive system and breast disorders
PROSTATITIS	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	2/44 (4.5%)	2
DYSPNOEA	1/44 (2.3%)	1
PULMONARY EMBOLISM	1/44 (2.3%)	1
PULMONARY HAEMORRHAGE	1/44 (2.3%)	1
RESPIRATORY DISTRESS	1/44 (2.3%)	1
Skin and subcutaneous tissue disorders
RASH	1/44 (2.3%)	1
Vascular disorders
DEEP VEIN THROMBOSIS	2/44 (4.5%)	2
Other (Not Including Serious) Adverse Events
	TG4010/Chemotherapy/Nivolumab
	Affected / at Risk (%)	# Events
Total	43/44 (97.7%)
Blood and lymphatic system disorders
ANAEMIA	24/44 (54.5%)	43
LEUKOPENIA	5/44 (11.4%)	5
NEUTROPENIA	14/44 (31.8%)	21
THROMBOCYTOPENIA	13/44 (29.5%)	20
Endocrine disorders
HYPOTHYROIDISM	4/44 (9.1%)	4
Eye disorders
LACRIMATION INCREASED	3/44 (6.8%)	3
Gastrointestinal disorders
ABDOMINAL PAIN	4/44 (9.1%)	5
CONSTIPATION	16/44 (36.4%)	17
DIARRHOEA	17/44 (38.6%)	23
DRY MOUTH	3/44 (6.8%)	3
GASTROOESOPHAGEAL REFLUX DISEASE	3/44 (6.8%)	3
NAUSEA	26/44 (59.1%)	31
STOMATITIS	7/44 (15.9%)	8
VOMITING	8/44 (18.2%)	10
General disorders
ASTHENIA	3/44 (6.8%)	3
FATIGUE	29/44 (65.9%)	39
INJECTION SITE ERYTHEMA	5/44 (11.4%)	6
INJECTION SITE PAIN	5/44 (11.4%)	5
INJECTION SITE REACTION	6/44 (13.6%)	6
OEDEMA PERIPHERAL	9/44 (20.5%)	11
PYREXIA	5/44 (11.4%)	7
Infections and infestations
CONJUNCTIVITIS	5/44 (11.4%)	5
Injury, poisoning and procedural complications
INFUSION RELATED REACTION	3/44 (6.8%)	3
Investigations
ALANINE AMINOTRANSFERASE INCREASED	4/44 (9.1%)	4
ASPARTATE AMINOTRANSFERASE INCREASED	5/44 (11.4%)	5
BLOOD CREATININE INCREASED	7/44 (15.9%)	7
LIPASE INCREASED	3/44 (6.8%)	3
WEIGHT DECREASED	8/44 (18.2%)	8
Metabolism and nutrition disorders
DECREASED APPETITE	13/44 (29.5%)	15
HYPOKALAEMIA	9/44 (20.5%)	13
Musculoskeletal and connective tissue disorders
MYALGIA	6/44 (13.6%)	6
PAIN IN EXTREMITY	5/44 (11.4%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN	4/44 (9.1%)	4
Nervous system disorders
DIZZINESS	4/44 (9.1%)	4
DYSGEUSIA	8/44 (18.2%)	8
HEADACHE	9/44 (20.5%)	9
PARAESTHESIA	8/44 (18.2%)	8
Respiratory, thoracic and mediastinal disorders
COUGH	12/44 (27.3%)	13
DYSPNOEA	13/44 (29.5%)	14
EPISTAXIS	4/44 (9.1%)	5
PRODUCTIVE COUGH	3/44 (6.8%)	3
Skin and subcutaneous tissue disorders
ALOPECIA	3/44 (6.8%)	3
DRY SKIN	7/44 (15.9%)	7
PRURITUS	4/44 (9.1%)	4
RASH	7/44 (15.9%)	9
Vascular disorders
FLUSHING	3/44 (6.8%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.