MYL-1402O Compared With Avastin®, in Patients With Stage IV nsNSCLC

• Sponsor: Mylan Pharmaceuticals Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04633564
• Collaborator: (none)
• Enrollment: 671
• Locations: 102
• Arms: 2
• Actual Duration (Months): 34
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Assess the Efficacy and Safety of MYL-1402O Compared with Avastin®, in the First-line Treatment of Patients with Stage IV Non-Squamous Non-Small Cell Lung Cancer

Condition or Disease	Intervention/Treatment	Phase
NSCLC Stage IV	Biological: Bevacizumab as MYL-1402O; Biological: Bevacizumab as Avastin	Phase 3

Detailed Description

MYL-1402O is a monoclonal antibody currently being developed by Mylan GmbH, as a proposed biosimilar to European Union and US licensed Avastin (hereafter referred to as Avastin), which is approved as first line treatment in combination with carboplatin and paclitaxel (CP) for patients with Stage IV unresectable, recurrent or metastatic nsNSCLC. This randomized equivalence study is designed to meet the global regulatory requirement for approval of a biosimilar product. For this study, both MYL-1402O and Avastin are considered investigational medicinal products (IMP).

Study Design

• Study Type: Interventional
• Actual Enrollment: 671 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicenter, Double-Blind, Randomized, Parallel-GroupMulticenter, Double-Blind, Randomized, Parallel-Group
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind
• Primary Purpose: Treatment
• Official Title: Multicenter, Double-Blind, Randomized, Parallel-Group Study to Assess the Efficacy and Safety of MYL-1402O Compared With Avastin®, in the First-line Treatment of Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
• Actual Study Start Date: Jan 21, 2017
• Actual Primary Completion Date: Jun 5, 2019
• Actual Study Completion Date: Nov 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MYL-1402O Patients will begin Period 1 receiving bevacizumab combination therapy (MYL-1402O15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as MYL-1402O ). In Period 2, eligible patients will continue to receive bevacizumab ( MYL- 1402O) every 3 weeks as monotherapy.	Biological: Bevacizumab as MYL-1402O; Bevacizumab as MYL-1402O 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV
Active Comparator: Avastin Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin). In Period 2, eligible patients will continue to receive bevacizumab (Avastin) every 3 weeks as monotherapy.	Biological: Bevacizumab as Avastin; Bevacizumab as Avastin 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV

Outcome Measures

Primary Outcome Measures

1. Primary Efficacy Analysis of Overall Response Rate ( ORR) of MYL-1402O as Compared to Avastin [18 weeks after first dosing per patient]

   The primary efficacy endpoint Overall Response Rate (ORR) will be based on best tumor responses as assessed by an independent review at any time point during the first 18 weeks, and assessed according to RECIST 1.1. The primary efficacy analysis is based on the ratio of the MYL-1402O ORR to the Avastin ORR at Week 18 based on the Intent to Treat ( ITT) set of patients.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

1. Written and signed informed consent

2. Male or female at least 18 years of age with documented imaging diagnosis of Stage IV unresectable, recurrent or metastatic nsNSCLC with at least one measurable lesion as defined by RECIST 1.1

3. Documented histologic or cytologic diagnosis of advanced nsNSCLC with negative or unknown sensitizing epidermal growth factor receptor (EGFR) mutation, and negative or unknown echinoderm microtubule-associated protein like 4 anaplastic lymphoma kinase (EML4 ALK) rearrangement.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

5. Has not received any prior systemic therapy for first-line treatment of advanced lung cancer, except adjuvant chemotherapy, and remained disease-free for at least 12 months from time of surgery, and at least 6 months from last dose of chemotherapy.

6. Treated and stable brain metastasis.

Key Exclusion Criteria:

1. Documented squamous NSCLC or small cell type or large cell neuroendocrine histology

2. History of significant hemoptysis, central tumors with proximity to large vessels and tumor with cavitation

3. Received prior treatment with paclitaxel, bevacizumab or anthracycline or had known hypersensitivity to any of these components.

4. Recent significant cardiac condition or vascular event or inadequately controlled hypertension.

5. On anticoagulant therapy not considered stable

6. Risk of hemorrhage in the central nervous system

7. Recent history of surgery, nonhealing wound, active ulcer, or untreated bone fracture.

8. History of gastrointestinal fistula, perforation, or abscess.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Grodno Clinical Regional Hospital	Grodno	Hrodzenskaya Voblasts	Belarus	230017
2	Mogilev Regional Oncology Dispensary	Minsk	Minskaya Voblasts	Belarus	220013
3	Babruysk Interregional Oncological Dispensary	Babruysk		Belarus	213825
4	State Institution NN Alexandrov Republican Scientific and Practical Centre of Oncology And Medical R	Minsk		Belarus	223040
5	Grodno Clinical Regional Hospital	Mogilev		Belarus	212018
6	Clinical Hospital Mostar	Mostar		Bosnia and Herzegovina
7	Clinical Center University of Sarajevo	Sarajevo		Bosnia and Herzegovina	71000
8	Javna zdravstvena ustanova bolnica Trebinje	Trebinje		Bosnia and Herzegovina	89101
9	County Hospital Zenica	Zenica		Bosnia and Herzegovina
10	Complex Oncology Center-Veliko Tarnovo	Veliko Tarnovo		Bulgaria	5000
11	Complex Oncology Center - Vratsa EOOD	Vratsa		Bulgaria	30001
12	Clinical Hospital Centre Osijek	Osijek		Croatia	31000
13	General Hospital Sibenik	Sibenik		Croatia	22000
14	Clinical Hospital Center Zagreb - PPDS	Zagreb		Croatia	10000
15	Research Institute of Clinical Medicine	Tbilisi		Georgia	112
16	LTD High Technology Medical Center University Clinic	Tbilisi		Georgia	144
17	Orszagos Koranyi Pulmonologiai Intezet	Budapest		Hungary
18	Semmelweis Egyetem	Budapest		Hungary
19	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary
20	Veszprem Megyei Tudogyogyintezet	Farkasgyepü		Hungary
21	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktató Kórház	Miskolc		Hungary
22	City Cancer Center	Vijayawada	Andhra Pradesh	India	520002
23	Mahatma Gandhi Medical College and Hospital	Visakhapatnam	Andhra Pradesh	India	530017
24	Regional Cancer Centre Indira Gandhi Institute of Medical Sciences	Patna	Bihar	India	800014
25	HCG Cancer Center	Ahmedabad	Gujarat	India	380060
26	Shree Giriraj Multispeciality Hospital	Rajkot	Gujarat	India	360005
27	Synexus Affiliate - Apple Hospital	Surat	Gujarat	India	395002
28	Unique Hospital - Multispeciality & Research Institute	Surat	Gujarat	India	395002
29	Aadhar Health Institute	Hisar	Haryana	India	125001
30	BGS Global Hospital	Bangalore	Karnataka	India	560060
31	Sri Venkateshwara Hospital	Bangalore	Karnataka	India	560068
32	Shetty's Hospital	Bengaluru	Karnataka	India	560068
33	Amravati Cancer Foundation Sujan Surgical and Cancer Hospital	Amravati	Maharashtra	India	444606
34	United CIIGMA Institute of Medical Sciences Pvt.Ltd.	Aurangabad	Maharashtra	India	431005
35	Seth Nandlal Dhoot Hospital	Aurangabad	Maharashtra	India	431210
36	Government Medical College	Nagpur	Maharashtra	India	440003
37	Curie Manavata Cancer Centre	Nashik	Maharashtra	India	422004
38	Ruby Hall Clinic	Pune	Maharashtra	India	411001
39	Acharya Tulsi Regional Cancer Institute and Research Centre	Bikaner	Rajasthan	India	334003
40	Malpani Multispecialty Hospital	Jaipur	Rajasthan	India	302013
41	Institute of Respiratory Diseases (Chest and TB Hospital)	Jaipur	Rajasthan	India	302016
42	Apex Hospital	Jaipur	Rajasthan	India	302017
43	Bhagwan Mahaveer Cancer Hospital and Research Centre	Jaipur	Rajasthan	India	302017
44	Rajiv Gandhi Government General Hospital	Chennai	Tamil Nadu	India	600003
45	Meenakshi Mission Hospital and Research Center	Madurai	Tamil Nadu	India	625107
46	Shatabdi Superspeciality Hospital	Lucknow	Uttar Pradesh	India	226003
47	Chittaranjan National Cancer Institute	Kolkata	West Bengal	India	700026
48	KLES Dr Prabhakar Kore Hospital and Medical Research Centre	Belagave		India	590010
49	Prince Aly Khan Hospital Mumbai	Mumbai		India	400010
50	Jaslok Hospital and Research Centre	Mumbai		India	400026
51	Sahyadri Speciality Hospital	Pune		India	411004
52	Kailash Cancer Hospital and Research Centre	Vadodara		India	391760
53	Ospedale Felice Lotti De Pontedera	Pontedera		Italy	56025
54	Philippine General Hospital	Manila	National Capital Region	Philippines	1000
55	Cardinal Santos Medical Center	San Juan City	National Capital Region	Philippines	1502
56	Med-Polonia Sp. z o.o.	Poznań		Poland	60-693
57	Radomskie Centrum Onkologii	Radom		Poland	26-600
58	Medisprof SRL	Cluj-Napoca	Cluj	Romania	400641
59	Ploiesti Municipal Hospital	Ploiesti	Prahova	Romania	100337
60	Spitalul Judetean de Urgenta Sf. Pantelimon Focsani	Focsani	Vrancea	Romania	620165
61	Elias Emergency University Hospital	Bucharest		Romania	11461
62	Prof. Dr. Alexandru Trestioreanu Oncologic Institute	Bucharest		Romania	22328
63	Spitalul Clinic Judetean de Urgenta Sf. Apostol Andrei Constanta	Constanta		Romania	900591
64	Oncology Center Sfantul Nectarie	Craiova		Romania
65	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangelsk		Russian Federation	163045
66	Chelyabinsk Regional Clinical Oncology Dispensary	Chelyabinsk		Russian Federation	454087
67	Kaluga Regional Oncology Dispensary	Kaluga		Russian Federation	248007
68	Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic	Kazan		Russian Federation	420029
69	Kursk Regional Oncology Centre	Kursk		Russian Federation	305524
70	Vitamed	Moscow		Russian Federation	129515
71	City Clinical Hospital #1	Novosibirsk		Russian Federation	630047
72	Clinical Oncology Dispensary	Omsk		Russian Federation	644013
73	Stavropol Regional Clinical Oncology Centre Pyatigorsk Affiliate	Pyatigorsk		Russian Federation	357502
74	Ryazan State Medical University n.a. I.P. Pavlov	Ryazan		Russian Federation	390011
75	Mordovia State University	Saransk		Russian Federation	430000
76	Research Institute of Phtisio-pneumology	St. Petersburg		Russian Federation	191036
77	Leningrad Regional Clinical Hospital	St. Petersburg		Russian Federation	194291
78	Railway Clinical Hospital JSC RZhD	St. Petersburg		Russian Federation	195271
79	Clinical Theoretical and Practical Center of Specialized Kinds of Medical Care	St. Petersburg		Russian Federation	197758
80	Scientific Research Institute of Oncology n.a. N.N. Petrov	St. Petersburg		Russian Federation	197758
81	City Clinical Oncology Dispensary	St. Petersburg		Russian Federation	198255
82	Research Oncology Institute of Tomsk Scientific Center	Tomsk		Russian Federation	634028
83	Volgograd Regional Clinical Oncology Dispensary	Volgograd		Russian Federation	400138
84	Regional Clinical Oncology Hospital	Yaroslavl		Russian Federation	150040
85	Hospital Universitario Vall d'Hebrón - PPDS	Barcelona		Spain	8035
86	Hospital Son Llatzer	Palma de Mallorca		Spain	7198
87	Kaohsiung Medical University Hospital	Kaohsiung		Taiwan	807
88	E-DA hospital	Kaohsiung		Taiwan	82544
89	Taichung Veterans General Hospital	Taichung		Taiwan	40705
90	Mackay Memorial Hospital-Taipei branch	Taipei		Taiwan	10449
91	Gazi University Medical Faculty Gazi Hospital	Ankara		Turkey	6500
92	Ege Universitesi Tip Fakultesi Hastanesi	Izmir		Turkey	35100
93	Municipal Institution City Clinical Hospital #4 of Dnipro City Council - PPDS	Dnipropetrovsk		Ukraine	49102
94	Municipal Institution SubCarpathian ClinicalOncological Centre	Ivano-Frankivsk		Ukraine	76018
95	MI Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council	Kryvyi Rih		Ukraine	50048
96	Municipal non profit enterprise of Sumy Regional Council Sumy Regional Clinical Oncology Dispensary	Sumy		Ukraine	40022
97	MNPE Central City Clinical Hospital of Uzhhorod City Council	Uzhgorod		Ukraine	88000
98	MI of Zaporizhzhia Regional Council Zaporizhzhia Regional Clinical Oncology Dispensary	Zaporizhzhia		Ukraine	69040
99	Bach Mai Hospital	Hanoi		Vietnam	100000
100	National Cancer Hospital	Hanoi		Vietnam	100000
101	National Lung Hospital	Hanoi		Vietnam	100000
102	Cho Ray Hospital	Ho Chi Minh City		Vietnam	700000

Sponsors and Collaborators

• Mylan Pharmaceuticals Inc

Investigators

• Study Director: Tazeen A Idris, MD,

Study Documents (Full-Text)

• Study Protocol - Feb 19, 2019
• Statistical Analysis Plan - Aug 21, 2019

More Information

Publications

None provided.

• Responsible Party: Mylan Pharmaceuticals Inc
• ClinicalTrials.gov Identifier: NCT04633564
• Other Study ID Numbers: MYL-1402O-3001
• First Posted: Nov 18, 2020
• Last Update Posted: Mar 16, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Bevacizumab

Study Results

Participant Flow

Recruitment Details	671 subjects enrolled at 89 sites across Eastern Europe, Russia, Asia Pacific, South East Asia. Date of first patient randomized: 21 Jan 2017 Date of last patient randomized: 31 Jan 2019
Pre-assignment Detail	A total of 1016 patients were screened; 345 patients were screen failures. Most common reasons for screen failures were; 57=met exclusion criteria tumor location in contact with major vessels, 46= withdrew consent; 37= patients who have brain metastasis which was treated and stable at the time of signing ICF and 36= patients did not have at least 1 measurable lesion as defined by RECIST 1.1.

Arm/Group Title	MYL-1402O	Avastin
Arm/Group Description	Patients will begin Period 1 receiving bevacizumab combination therapy (MYL-1402O15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as MYL-1402O ). In Period 2, eligible patients will continue to receive bevacizumab ( MYL- 1402O) every 3 weeks as monotherapy. Bevacizumab as MYL-1402O: Bevacizumab as MYL-1402O 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV	Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin). In Period 2, eligible patients will continue to receive bevacizumab (Avastin) every 3 weeks as monotherapy. Bevacizumab as Avastin: Bevacizumab as Avastin 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV
Period Title: Period 1
STARTED	335	329
COMPLETED	227	220
NOT COMPLETED	108	109
Period Title: Period 1
STARTED	200	199
COMPLETED	107	102
NOT COMPLETED	93	97

Baseline Characteristics

Arm/Group Title	MYL-1402O	Avastin	Total
Arm/Group Description	Patients will begin Period 1 receiving bevacizumab combination therapy (MYL-1402O15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as MYL-1402O ). In Period 2, eligible patients will continue to receive bevacizumab ( MYL- 1402O) every 3 weeks as monotherapy. Bevacizumab as MYL-1402O: Bevacizumab as MYL-1402O 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV	Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin). In Period 2, eligible patients will continue to receive bevacizumab (Avastin) every 3 weeks as monotherapy. Bevacizumab as Avastin: Bevacizumab as Avastin 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV	Total of all reporting groups
Overall Participants	337	334	671
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	237 70.3%	236 70.7%	473 70.5%
>=65 years	100 29.7%	98 29.3%	198 29.5%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.3 (9.60)	59.2 (9.73)	59.3 (9.66)
Sex: Female, Male (Count of Participants)
Female	124 36.8%	123 36.8%	247 36.8%
Male	213 63.2%	211 63.2%	424 63.2%
Race/Ethnicity, Customized (Count of Participants)
White	226 67.1%	232 69.5%	458 68.3%
Asian	111 32.9%	102 30.5%	213 31.7%
Region of Enrollment (participants) [Number]
Romania	3 0.9%	4 1.2%	7 1%
Hungary	15 4.5%	14 4.2%	29 4.3%
Philippines	1 0.3%	1 0.3%	2 0.3%
Ukraine	86 25.5%	74 22.2%	160 23.8%
Belarus	12 3.6%	12 3.6%	24 3.6%
India	99 29.4%	92 27.5%	191 28.5%
Russia	65 19.3%	75 22.5%	140 20.9%
Spain	2 0.6%	1 0.3%	3 0.4%
Vietnam	10 3%	7 2.1%	17 2.5%
Turkey	1 0.3%	1 0.3%	2 0.3%
Taiwan	1 0.3%	2 0.6%	3 0.4%
Poland	3 0.9%	2 0.6%	5 0.7%
Georgia	28 8.3%	30 9%	58 8.6%
Bulgaria	3 0.9%	4 1.2%	7 1%
Bosnia and Herzegovina	8 2.4%	11 3.3%	19 2.8%
Croatia	0 0%	4 1.2%	4 0.6%

Outcome Measures

1. Primary Outcome

Title	Primary Efficacy Analysis of Overall Response Rate ( ORR) of MYL-1402O as Compared to Avastin
Description	The primary efficacy endpoint Overall Response Rate (ORR) will be based on best tumor responses as assessed by an independent review at any time point during the first 18 weeks, and assessed according to RECIST 1.1. The primary efficacy analysis is based on the ratio of the MYL-1402O ORR to the Avastin ORR at Week 18 based on the Intent to Treat ( ITT) set of patients.
Time Frame	18 weeks after first dosing per patient

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis was conducted in the Intent To Treat population (ITT)

Arm/Group Title	MYL-1402O	Avastin
Arm/Group Description	Patients will begin Period 1 receiving bevacizumab combination therapy (MYL-1402O15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as MYL-1402O ). In Period 2, eligible patients will continue to receive bevacizumab ( MYL- 1402O) every 3 weeks as monotherapy. Bevacizumab as MYL-1402O: Bevacizumab as MYL-1402O 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV	Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin). In Period 2, eligible patients will continue to receive bevacizumab (Avastin) every 3 weeks as monotherapy. Bevacizumab as Avastin: Bevacizumab as Avastin 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV
Measure Participants	337	334
Responders	140 41.5%	144 43.1%
Non-Responders	197 58.5%	190 56.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MYL-1402O, Avastin
	Comments
	Type of Statistical Test	Equivalence
	Comments	The equivalence region is (0.73, 1.36).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 90%; 0.83 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Active collection period of AEs will be from the time the patient signs the ICF through the Safety Follow Up Visit. Pre-existing diseases or conditions (reported at time of screening) will not be considered AEs unless there is an increase in the frequency or severity, or a change in the quality of the disease or condition. Progression of NSCLC and its consequences will not be collected as an AE even if they lead to hospitalization or meet any other seriousness criteria including death.
Adverse Event Reporting Description	The Investigator is responsible for the detection and documentation of events meeting the criteria and definition of an AE or SAE. At each visit, the patient will be allowed time to spontaneously report any issues since the last visit or evaluation. The Investigator will then monitor and/or ask about or evaluate AEs using non-leading questions. Any clinically relevant observations made during the visit are also to be considered AEs.
Arm/Group Title	MYL-1402O		Avastin
Arm/Group Description	Patients will begin Period 1 receiving bevacizumab combination therapy (MYL-1402O15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as MYL-1402O ). In Period 2, eligible patients will continue to receive bevacizumab ( MYL- 1402O) every 3 weeks as monotherapy. Bevacizumab as MYL-1402O: Bevacizumab as MYL-1402O 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV		Patients will begin Period 1 receiving bevacizumab combination therapy ( Avastin15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV) on Day 0 of Cycle 1 for up to 6 cycles of therapy. Each cycle will consist of 3 weeks (21 days ± 3 days) and a cycle will start with the administration of bevacizumab (as Avastin). In Period 2, eligible patients will continue to receive bevacizumab (Avastin) every 3 weeks as monotherapy. Bevacizumab as Avastin: Bevacizumab as Avastin 15 mg/kg IV + Carboplatin AUC 6 IV+ Paclitaxel 200 or 175 mg/m2 IV
All Cause Mortality
	MYL-1402O		Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	101/335 (30.1%)		82/329 (24.9%)
Serious Adverse Events
	MYL-1402O		Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/335 (17.6%)		55/329 (16.7%)
Blood and lymphatic system disorders
Febrile Neutropenia	7/335 (2.1%)		5/329 (1.5%)
Thrombocytopenia	4/335 (1.2%)		6/329 (1.8%)
Anaemia	5/335 (1.5%)		1/329 (0.3%)
Neutropenia	4/335 (1.2%)		2/329 (0.6%)
Leukopenia	2/335 (0.6%)		1/329 (0.3%)
Coagulopathy	0/335 (0%)		1/329 (0.3%)
Pancytopenia	0/335 (0%)		1/329 (0.3%)
Cardiac disorders
Acute Coronary Syndrome	1/335 (0.3%)		0/329 (0%)
Angina Unstable	0/335 (0%)		1/329 (0.3%)
Atrial Fibrillation	1/335 (0.3%)		0/329 (0%)
Cardicac Arrest	1/335 (0.3%)		0/329 (0%)
Cardiac Failure Acute	0/335 (0%)		1/329 (0.3%)
Cardio-Respiratory Arrest	1/335 (0.3%)		0/329 (0%)
COR Pulmonale Acute	1/335 (0.3%)		0/329 (0%)
Coronary Artery disease	0/335 (0%)		1/329 (0.3%)
Myocardial Infarction	1/335 (0.3%)		0/329 (0%)
Ventricular Arrhythmia	0/335 (0%)		1/329 (0.3%)
Eye disorders
Angle Closure Glaucoma	1/335 (0.3%)		0/329 (0%)
Gastrointestinal disorders
Diarrhoea	1/335 (0.3%)		3/329 (0.9%)
Vomiting	2/335 (0.6%)		0/329 (0%)
Duodenal Ulcer	0/335 (0%)		1/329 (0.3%)
Duodenal Ulcer Haemorrhage	0/335 (0%)		1/329 (0.3%)
Gastric Perforation	1/335 (0.3%)		0/329 (0%)
Gastric Ulcer Haemorrhage	1/335 (0.3%)		0/329 (0%)
Gastrointestinal Haemorrhage	0/335 (0%)		1/329 (0.3%)
Ileus	0/335 (0%)		1/329 (0.3%)
Large Intestine Perforation	0/335 (0%)		1/329 (0.3%)
Peptic Ulcer Haemorrhage	0/335 (0%)		1/329 (0.3%)
Peptic Ulcer Perforation	0/335 (0%)		1/329 (0.3%)
Proctitis	0/335 (0%)		1/329 (0.3%)
General disorders
Pyrexia	1/335 (0.3%)		3/329 (0.9%)
Impaired Healing	0/335 (0%)		1/329 (0.3%)
Multiple Organ Dysfunction Syndrome	0/335 (0%)		1/329 (0.3%)
Hepatobiliary disorders
Cholecystitis	0/335 (0%)		1/329 (0.3%)
Immune system disorders
Hypersensitivity	1/335 (0.3%)		0/329 (0%)
Infections and infestations
Sepsis	3/335 (0.9%)		2/329 (0.6%)
Pneumonia	3/335 (0.9%)		1/329 (0.3%)
Gastroenteritis	3/335 (0.9%)		0/329 (0%)
Infectious Pleural Effusion	2/335 (0.6%)		1/329 (0.3%)
Peritonitis	0/335 (0%)		2/329 (0.6%)
Cellulitis	1/335 (0.3%)		0/329 (0%)
Ear Infection	0/335 (0%)		1/329 (0.3%)
Eye Infection Fungal	0/335 (0%)		1/329 (0.3%)
Gastroenteritis Salmonella	0/335 (0%)		1/329 (0.3%)
Gastrointestinal Infection	1/335 (0.3%)		0/329 (0%)
Hepatitis C	0/335 (0%)		1/329 (0.3%)
Herpes Zoster	1/335 (0.3%)		0/329 (0%)
Lung Infection	0/335 (0%)		1/329 (0.3%)
Rectal Abscess	1/335 (0.3%)		0/329 (0%)
Respiratory Tract Infection	1/335 (0.3%)		0/329 (0%)
Septic Shock	1/335 (0.3%)		0/329 (0%)
Injury, poisoning and procedural complications
Femur Fracture	1/335 (0.3%)		0/329 (0%)
Investigations
Platelet Count Decreased	1/335 (0.3%)		0/329 (0%)
Metabolism and nutrition disorders
Hyponatraemia	1/335 (0.3%)		1/329 (0.3%)
Musculoskeletal and connective tissue disorders
Pathological Fracture	0/335 (0%)		1/329 (0.3%)
Nervous system disorders
Cererovascular accident	2/335 (0.6%)		1/329 (0.3%)
Cerebral Small Vessel Ischamic Disease	1/335 (0.3%)		0/329 (0%)
Hemiparesis	1/335 (0.3%)		0/329 (0%)
Renal and urinary disorders
Acute Kidney Injury	0/335 (0%)		2/329 (0.6%)
Cystitis Haemorrhagic	0/335 (0%)		1/329 (0.3%)
Pyelocalieectasis	0/335 (0%)		1/329 (0.3%)
Renal Cyst Ruptured	0/335 (0%)		1/329 (0.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	4/335 (1.2%)		4/329 (1.2%)
Pulmonary Haemorrhage	4/335 (1.2%)		3/329 (0.9%)
Dyspnoea	5/335 (1.5%)		1/329 (0.3%)
Haemoptysis	1/335 (0.3%)		2/329 (0.6%)
Pneumothorax	2/335 (0.6%)		1/329 (0.3%)
Chronic Obstructive Pulmonary Disease	1/335 (0.3%)		1/329 (0.3%)
Pleural Effusion	2/335 (0.6%)		0/329 (0%)
Acute Respiratory Distress Syndrome	0/335 (0%)		1/329 (0.3%)
Aspiration	1/335 (0.3%)		0/329 (0%)
Pneumomediastinum	0/335 (0%)		1/329 (0.3%)
Pulmonary Oedema	1/335 (0.3%)		0/329 (0%)
Pulmonary Thrombosis	0/335 (0%)		1/329 (0.3%)
Respiratory Failure	1/335 (0.3%)		0/329 (0%)
Vascular disorders
Deep Vein Thrombosis	1/335 (0.3%)		1/329 (0.3%)
Hypertensive crisis	2/335 (0.6%)		0/329 (0%)
Hypertension	0/335 (0%)		1/329 (0.3%)
Hypotension	0/335 (0%)		1/329 (0.3%)
Venous Thrombosis	0/335 (0%)		1/329 (0.3%)
Other (Not Including Serious) Adverse Events
	MYL-1402O		Avastin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	311/335 (92.8%)		304/329 (92.4%)
Blood and lymphatic system disorders
Anaemia	111/335 (33.1%)		112/329 (34%)
Thrombocytopenia	104/335 (31%)		80/329 (24.3%)
Neutropenia	68/335 (20.3%)		76/329 (23.1%)
Leukopenia	38/335 (11.3%)		41/329 (12.5%)
Gastrointestinal disorders
Nausea	56/335 (16.7%)		49/329 (14.9%)
Vomiting	54/335 (16.1%)		38/329 (11.6%)
Diarrhoea	46/335 (13.7%)		30/329 (9.1%)
Stomatitis	22/335 (6.6%)		8/329 (2.4%)
General disorders
Asthenia	53/335 (15.8%)		33/329 (10%)
Pyrexia	31/335 (9.3%)		21/329 (6.4%)
Fatigue	26/335 (7.8%)		27/329 (8.2%)
Investigations
Alanine Aminotranferase Increased	25/335 (7.5%)		29/329 (8.8%)
Aspartate Aminotransferase Increased	22/335 (6.6%)		19/329 (5.8%)
Weight decreased	22/335 (6.6%)		7/329 (2.1%)
Metabolism and nutrition disorders
Decreased Appetite	43/335 (12.8%)		32/329 (9.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	16/335 (4.8%)		18/329 (5.5%)
Nervous system disorders
Peripheral Sensory Neuropathy	74/335 (22.1%)		66/329 (20.1%)
Headache	26/335 (7.8%)		17/329 (5.2%)
Hypoaesthesia	15/335 (4.5%)		20/329 (6.1%)
Renal and urinary disorders
Proteinuria	11/335 (3.3%)		17/329 (5.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	21/335 (6.3%)		16/329 (4.9%)
Cough	15/335 (4.5%)		23/329 (7%)
Epistaxis	6/335 (1.8%)		17/329 (5.2%)
Skin and subcutaneous tissue disorders
Alopecia	148/335 (44.2%)		168/329 (51.1%)
Vascular disorders
Hypertension	19/335 (5.7%)		16/329 (4.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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