Trial to Compare the Safety, Efficacy and Immunogenicity of TX05 With Herceptin® in HER2+ Early Breast Cancer

• Sponsor: Tanvex BioPharma USA, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03556358
• Collaborator: (none)
• Enrollment: 809
• Locations: 146
• Arms: 2
• Actual Duration (Months): 31.3
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Phase III, double-blind, randomized, multicenter study to compare the efficacy and to evaluate the safety and immunogenicity of TX05 (trastuzumab) with Herceptin® in subjects with HER2 positive early breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Breast Neoplasms; HER2-positive Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer	Biological: TX05 (trastuzumab); Biological: Herceptin®; Drug: Paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 809 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Parallel Group, Phase III Trial to Compare the Efficacy, Safety, and Immunogenicity of TX05 With Herceptin® in Subjects With HER2 Positive Early Breast Cancer
• Actual Study Start Date: Jun 28, 2018
• Actual Primary Completion Date: Nov 27, 2020
• Actual Study Completion Date: Feb 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TX05 (trastuzumab) • Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles	Biological: TX05 (trastuzumab); 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8); Drug: Paclitaxel; 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8); Other Names: Ribotax ; Drug: Epirubicin; 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4); Drug: Cyclophosphamide; 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
Active Comparator: Herceptin® • Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles	Biological: Herceptin®; 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8); Drug: Paclitaxel; 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8); Other Names: Ribotax ; Drug: Epirubicin; 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4); Drug: Cyclophosphamide; 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) [3-7 weeks following last dose of study treatment]

   Pathologic complete response was determined by central review and defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled lymph nodes following neoadjuvant systemic therapy (ypT0/Tis ypN0).

Secondary Outcome Measures

1. Objective Response Rate (ORR) [End of Treatment (Week 24) or Early Termination Visit]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (ORR) = CR + PR.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Histologically confirmed HER 2 overexpressing invasive primary operable Stage II/IIIa breast cancer (AJCC version 7 staging criteria).

• Available tumor tissue for central review of HER2 status.

• Planned surgical resection of breast tumor.

• Planned neoadjuvant chemotherapy.

• Documentation of HER2 gene amplification or overexpression.

• Ipsilateral, measurable tumor longest diameter > 2 cm.

• Known estrogen receptor (ER) and progesterone receptor (PR) hormone status (may be performed during screening).

• ECOG performance status of 0 or 1.

• Adequate bone marrow, hepatic and renal functions.

• Left ventricular ejection fraction (LVEF) ≥ 50% or within institutional normal limits, measured by echocardiography or MUGA scan.

• Effective contraception as defined by protocol.

Key Exclusion Criteria:

• Investigational therapy within 2 months of first dose of study drug.

• Bilateral breast cancer.

• Inflammatory breast cancer

• Metastases.

• Prior chemotherapy, biologic therapy, radiation or surgery for any active malignancy, including breast cancer.

• Cardiac insufficiency, myocardial infarction, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident, unstable angina pectoris, uncontrolled arrhythmia or pulmonary embolus within the previous 12 months prior to 1st administration of study drug.

• Clinically significant active infection, poorly controlled diabetes mellitus and/or uncontrolled hypertension.

• Major surgery, significant traumatic injury, radiation therapy and/or grade 3 hemorrhage within 4 weeks of 1st administration of study drug.

• Pre-existing clinically significant Grade 2 peripheral neuropathy.

• Malignancy within the last 5 years (except squamous/basal cell carcinoma of the skin, cervical carcinoma in situ and superficial bladder cancer).

• Severe dyspnea at rest requiring oxygen therapy.

• Known positive HIV, acute or chronic active infection with Hepatitis B or Hepatitis C.

• Current pregnancy or breastfeeding.

• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in normal range despite optimal therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tanvex Investigational Site 1008	Lesnoy	Minsk Region	Belarus	223040
2	Tanvex Investigational Site 1007	Babruysk	Mogilev Region	Belarus	213825
3	Tanvex Investigational Site 1003	Gomel		Belarus	246012
4	Tanvex Investigational Site 1006	Grodno		Belarus	230017
5	Tanvex Investigational Site 1002	Minsk		Belarus	220013
6	Tanvex Investigational Site 1005	Mogilev		Belarus	2120018
7	Tanvex Investigational Site 1001	Vitebsk		Belarus	21008
8	Tanvex Investigational Site 4001	Temuco		Chile	4810469
9	Tanvex Investigational Site 4002	Viña Del Mar		Chile	2520598
10	Tanvex Investigational Site 5006	Batumi		Georgia	6000
11	Tanvex Investigational Site 5002	Batumi		Georgia	6010
12	Tanvex Investigational Site 5003	Tbilisi		Georgia	0144
13	Tanvex Investigational Site 5001	Tbilisi		Georgia	0159
14	Tanvex Investigational Site 5005	Tbilisi		Georgia	0159
15	Tanvex Investigational Site 5012	Tbilisi		Georgia	0159
16	Tanvex Investigational Site 5013	Tbilisi		Georgia	0177
17	Tanvex Investigational Site 5004	Tbilisi		Georgia	0179
18	Tanvex Investigational Site 5010	Tbilisi		Georgia	0186
19	Tanvex Investigational Site 5011	Tbilisi		Georgia	0186
20	Tanvex Investigational Site 5008	Tbilisi		Georgia	112
21	Tanvex Investigational Site 5009	Tbilisi		Georgia	131
22	Tanvex Investigational Site 5007	Tbilisi		Georgia	141
23	Tanvex Investigational Site 6003	Budapest		Hungary	1122
24	Tanvex Investigational Site 6007	Budapest		Hungary	1122
25	Tanvex Investigational Site 6005	Debrecen		Hungary	4032
26	Tanvex Investigational Site 6006	Győr		Hungary	9024
27	Tanvex Investigational Site 6004	Miskolc		Hungary	3526
28	Tanvex Investigational Site 6001	Pécs		Hungary	7264
29	Tanvex Investigational Site 7007	Nashik	Maharashtra	India	422005
30	Tanvex Investigational Site 7015	Pune	Maharashtra	India	411001
31	Tanvex Investigational Site 7003	Pune	Maharashtra	India	411004
32	Tanvex Investigational Site 7004	Pune	Maharashtra	India	411004
33	Tanvex Investigational Site 7002	Bīkaner	Rajasthan	India	334003
34	Tanvex Investigational Site 7010	Madurai	Tamil Nadu	India	625107
35	Tanvex Invesitgational Site 7033	Ahmedabad		India	380016
36	Tanvex Investigational Site 7019	Bangalore		India	560027
37	Tanvex Investigational Site 7037	Bangalore		India	560072
38	Tanvex Investigational Site 7022	Belgaum		India	590010
39	Tanvex Investigational Site 7034	Chandigarh		India	160012
40	Tanvex Investigational Site 7013	Coimbatore		India	641037
41	Tanvex Investigational Site 7024	Gurgaon		India	122001
42	Tanvex Investigational Site 7045	Hyderabad		India	500004
43	Tanvex Investigational Site 7036	Hyderabad		India	500034
44	Tanvex Investigational Site 7009	Jaipur		India	302004
45	Tanvex Investigational Site 7039	Kolkata		India	700014
46	Tanvex Investigational Site 7040	Kolkata		India	700094
47	Tanvex Investigational Site 7006	Kolkata		India	700099
48	Tanvex Investigational Site 7005	Lucknow		India	226003
49	Tanvex Investigational Site 7012	Manipala		India	576104
50	Tanvex Investigational Site 7041	Model Town		India	141002
51	Tanvex Investigational Site 7031	Naka		India	422004
52	Tanvex Investigational Site 7001	Nashik		India	422002
53	Tanvex Investigational Site 7042	Trichy		India	620008
54	Tanvex Investigational Site 7018	Vadodara		India	390007
55	Tanvex Investigational Site 7017	Vijayawada		India	520002
56	Tanvex Investigational Site 2102	Monterrey	Nuevo León	Mexico	64000
57	Tanvex Investigational Site 2117	Aguascalientes		Mexico	20127
58	Tanvex Investigational Site 2109	Aguascalientes		Mexico	20234
59	Tanvex Investigational Site 2116	Cancun		Mexico	77506
60	Tanvex Investigational Site 2111	Ciudad de mexico		Mexico	06760
61	Tanvex Investigational Site 2104	Cuauhtemoc		Mexico	06100
62	Tanvex Investigational Site 2114	Cuauhtémoc		Mexico	06760
63	Tanvex Investigational Site 2101	Cuautitlán Izcalli		Mexico	54769
64	Tanvex Investigational Site 2113	Mexico		Mexico	06100
65	Tanvex Investigational Site 2103	Monterrey		Mexico	64320
66	Tanvex Investigational Site 2106	Oaxaca		Mexico	68000
67	Tanvex Investigational Site 2112	San Luis Potosí		Mexico	78200
68	Tanvex Investigational Site 2110	Tequisquiapan		Mexico	76750
69	Tanvex Investigational Site 2108	Zapopan		Mexico	45030
70	Tanvex Investigational Site 1104	Chiclayo	Lambayeque	Peru	14001
71	Tanvex Investigational Site 1112	Lima Cercado	Lima	Peru	15082
72	Tanvex Investigational Site 1108	San Borja	Lima	Peru	15036
73	Tanvex Investigational Site 1113	San Borja	Lima	Peru	15036
74	Tanvex Investigational Site 1101	Arequipa		Peru	04001
75	Tanvex Investigational Site 1107	Arequipa		Peru	04001
76	Tanvex Investigational Site 1110	Lima		Peru	15046
77	Tanvex Investigational Site 1105	San Isidro		Peru	15036
78	Tanvex Investigational Site 1102	San Isidro		Peru	15073
79	Tanvex Investigational Site 1109	Surquillo		Peru	15038
80	Tanvex Investigational Site 1103	Trujillo		Peru	13001
81	Tanvex Investigational Site 1210	Santo Tomas	Batangas	Philippines	4234
82	Tanvex Investigational Site 1203	Cebu City	Cebu	Philippines	6000
83	Tanvex Investigational Site 1204	Cebu City	Cebu	Philippines	6000
84	Tanvex Investigational Site 1211	Cebu City	Cebu	Philippines	6000
85	Tanvex Investigational Site 1208	Quezon City	Manila	Philippines	1110
86	Tanvex Investigational Site 1207	Manila	Metro Manila	Philippines	1000
87	Tanvex Investigational Site 1206	Bacolod City	Negros Occidental	Philippines	6100
88	Tanvex Investigational Site 1212	Davao City		Philippines	8000
89	Tanvex Investigational Site 1214	Makati City		Philippines	1229
90	Tanvex Investigational Site 1201	Manila		Philippines	1000
91	Tanvex Investigational Site 1209	Quezon City		Philippines	1101
92	Tanvex Investigational Site 1213	Quezon City		Philippines	1102
93	Tanvex Investigational Site 1529	Krasnodar	Krasnodar Region	Russian Federation	350040
94	Tanvex Investigational Site 1513	Sochi	Krasnodar Region	Russian Federation	354057
95	Tanvex Investigational Site 1509	Omsk	Omsk Region	Russian Federation	644013
96	Tanvex Investigational Site 1522	Ufa	Republic Of Bashkortostan	Russian Federation	450054
97	Tanvex Investigational Site 1510	Pushkin	Saint Petersburg	Russian Federation	196603
98	Tanvex Investigational Site 1511	Novosibirsk	Siberia	Russian Federation	630099
99	Tanvex Investigational Site 1519	Pyatigorsk	Stavropol Region	Russian Federation	357502
100	Tanvex Investigational Site 1518	Tomsk	Tomsk Region	Russian Federation	634050
101	Tanvex Investigational Site 1535	Arkhangel'sk		Russian Federation	163045
102	Tanvex Investigational Site 1531	Belgorod		Russian Federation	308010
103	Tanvex Investigational Site 1538	Chelyabinsk		Russian Federation	454048
104	Tanvex Investigational Site 1520	Ivanovo		Russian Federation	153040
105	Tanvex Investigational Site 1515	Izhevsk		Russian Federation	426009
106	Tanvex Investigational Site 1502	Kaluga		Russian Federation	248007
107	Tanvex Investigational Site 1540	Kazan		Russian Federation	420029
108	Tanvex Investigational Site 1512	Krasnoyarsk		Russian Federation	660133
109	Tanvex Investigational Site 1505	Kursk		Russian Federation	305035
110	Tanvex Investigational Site 1530	Moscow		Russian Federation	121467
111	Tanvex Investigational Site 1536	Moscow		Russian Federation	125284
112	Tanvex Investigational Site 1514	Moscow		Russian Federation	129128
113	Tanvex Investigational Site 1507	Moscow		Russian Federation	129515
114	Tanvex Investigational Site 1503	Omsk		Russian Federation	644013
115	Tanvex Investigational Site 1537	Orenburg		Russian Federation	460021
116	Tanvex Investigational Site 1521	Rostov-Na-Donu		Russian Federation	344037
117	Tanvex Investigational Site 1516	Saint Petersburg		Russian Federation	191015
118	Tanvex Investigational Site 1517	Saint Petersburg		Russian Federation	191025
119	Tanvex Investigational Site 1523	Saint Petersburg		Russian Federation	191104
120	Tanvex Investigational Site 1525	Saint Petersburg		Russian Federation	196247
121	Tanvex Investigational Site 1506	Saint Petersburg		Russian Federation	197758
122	Tanvex Investigational Site 1526	Saint Petersburg		Russian Federation	197758
123	Tanvex Investigational Site 1501	Saint Petersburg		Russian Federation	198255
124	Tanvex Investigational Site 1524	Saint-Petersburg		Russian Federation	195271
125	Tanvex Investigational Site 1508	Saransk		Russian Federation	430032
126	Tanvex Investigational Site 1533	Tomsk		Russian Federation	634009
127	Tanvex Investigational Site 1534	Yaroslavl		Russian Federation	150054
128	Tanvex Investigational Site 1808	Chernihiv		Ukraine	14029
129	Tanvex Investigational Site 1821	Chernivtsi		Ukraine	58013
130	Tanvex Investigational Site 1803	Dnepropetrovsk		Ukraine	49102
131	Tanvex Investigational Site 1824	Dnipro		Ukraine	49600
132	Tanvex Investigational Site 1820	Kherson		Ukraine	73000
133	Tanvex Investigational Site 1812	Khmelnytskyi		Ukraine	29000
134	Tanvex Investigational Site 1815	Kiev		Ukraine	03022
135	Tanvex Investigational Site 1811	Kiev		Ukraine	03115
136	Tanvex Investigational Site 1802	Kiev		Ukraine	04107
137	Tanvex Investigational Site 1814	Kirovogrado		Ukraine	25000
138	Tanvex Investigational Site 1819	Kropyvnytskyi		Ukraine	25006
139	Tanvex Investigational Site 1804	Kryvyi Rih		Ukraine	50048
140	Tanvex Investigational Site 1809	Kyiv		Ukraine	03126
141	Tanvex Investigational Site 1810	Odesa		Ukraine	65055
142	Tanvex Investigational Site 1806	Sumy		Ukraine	40022
143	Tanvex Investigational Site 1822	Ternopil'		Ukraine	46023
144	Tanvex Investigational Site 1818	Vinnitsya		Ukraine	21029
145	Tanvex Investigational Site 1813	Zaporizhzhia		Ukraine	69104
146	Tanvex Investigational Site 1823	Úzhgorod		Ukraine	88000

Sponsors and Collaborators

• Tanvex BioPharma USA, Inc.

Investigators

• Study Director: Bonnie Mills, PhD, Tanvex BioPharma USA, Inc.

Study Documents (Full-Text)

• Study Protocol - Nov 30, 2017
• Statistical Analysis Plan - Feb 4, 2021

More Information

Publications

None provided.

• Responsible Party: Tanvex BioPharma USA, Inc.
• ClinicalTrials.gov Identifier: NCT03556358
• Other Study ID Numbers: TX05-03
• First Posted: Jun 14, 2018
• Last Update Posted: Jan 14, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tanvex BioPharma USA, Inc.: trastuzumab; Herceptin
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Cyclophosphamide; Trastuzumab; Epirubicin

Study Results

Participant Flow

Recruitment Details	A total of 809 subjects were randomized to the study. Of these, 806 subjects initiated protocol treatment.
Pre-assignment Detail	Of the 806 subjects who initiated protocol treatment, 794 subjects initiated Cycle 5 (when trastuzumab was added); of these 394 subjects received TX05 and 400 subjects received Herceptin.

Arm/Group Title	TX05 (Trastuzumab)	Herceptin®
Arm/Group Description	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
Period Title: Overall Study
STARTED	404	405
Subjects Treated	401	405
Subjects Receiving TX05 or Herceptin	394	400
COMPLETED	393	393
NOT COMPLETED	11	12

Baseline Characteristics

Arm/Group Title	TX05 (Trastuzumab)	Herceptin®	Total
Arm/Group Description	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)	Total of all reporting groups
Overall Participants	394	400	794
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.2 (11.80)	53.4 (10.83)	53.8 (11.32)
Sex: Female, Male (Count of Participants)
Female	394 100%	400 100%	794 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	69 17.5%	71 17.8%	140 17.6%
Not Hispanic or Latino	325 82.5%	328 82%	653 82.2%
Unknown or Not Reported	0 0%	1 0.3%	1 0.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	15 3.8%	14 3.5%	29 3.7%
Asian	64 16.2%	72 18%	136 17.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 0.3%	1 0.1%
White	292 74.1%	286 71.5%	578 72.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	23 5.8%	27 6.8%	50 6.3%
Hormone Receptor Status (Count of Participants)
Positive	253 64.2%	254 63.5%	507 63.9%
Negative	141 35.8%	146 36.5%	287 36.1%
ECOG (Count of Participants)
Grade 0	316 80.2%	305 76.3%	621 78.2%
Grade 1	78 19.8%	95 23.8%	173 21.8%
Tumor Stage (Count of Participants)
IIA	142 36%	141 35.3%	283 35.6%
IIB	169 42.9%	173 43.3%	342 43.1%
IIIA	83 21.1%	86 21.5%	169 21.3%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR)
Description	Pathologic complete response was determined by central review and defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled lymph nodes following neoadjuvant systemic therapy (ypT0/Tis ypN0).
Time Frame	3-7 weeks following last dose of study treatment

Outcome Measure Data

Analysis Population Description

Per Protocol Population [includes all subjects who received at least one dose of study drug (TX05 or Herceptin) and had no major protocol deviations that impact the efficacy endpoints].

Arm/Group Title	TX05 (Trastuzumab)	Herceptin®
Arm/Group Description	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
Measure Participants	336	338
Subjects who do not Meet pCR Criteria	172 43.7%	185 46.3%
Subjects Meeting pCR Criteria	164 41.6%	153 38.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TX05 (Trastuzumab), Herceptin®
	Comments
	Type of Statistical Test	Equivalence
	Comments	Two one-sided hypothesis tests were performed for pCR in order to show that TX05 is equivalent to Herceptin: TEST 1: H0a: θ1 / θ2 > 1.325 vs. H1a: θ1 / θ2 < 1.325 TEST 2: H0b: θ1 / θ2 < 0.755 vs. H1b: θ1 / θ2 > 0.755 Where θ1 is the proportion of pCR for subjects randomized to TX05 group, θ2 is the proportion of pCR for subjects randomized to Herceptin. Equivalence was concluded if the 95% CI of the risk ratio is completely contained within the pre-defined interval [0.755, 1.325].
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.0783
	Confidence Interval	(2-Sided) 95%; 0.9185 to 1.2659
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (ORR) = CR + PR.
Time Frame	End of Treatment (Week 24) or Early Termination Visit

Outcome Measure Data

Analysis Population Description

This analysis was performed on the modified intent-to-treat population. The modified intent-to-treat (mITT) population includes all subjects who were randomized and received at least 1 dose of TX05 or Herceptin.

Arm/Group Title	TX05 (Trastuzumab)	Herceptin®
Arm/Group Description	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
Measure Participants	394	400
Count of Participants [Participants]	332 84.3%	340 85%

Adverse Events

Time Frame	Serious Adverse Events were recorded from Screening, while Adverse Events were recorded from Day 1 (Week 0) of Cycle 1 of study treatment through End of Treatment (Week 24).
Adverse Event Reporting Description	Because study drug (TX05/trastuzumab) was not introduced until Cycle 5 of treatment, the analyses of AEs was focused on Cycles 5 through 8 of treatment. The following results include events that occurred on or after initiation of TX05 or Herceptin treatment.
Arm/Group Title	TX05 (Trastuzumab)		Herceptin®
Arm/Group Description	• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)		• Intravenous (IV) epirubicin, 75 mg/m^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles Followed by: • IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8) Paclitaxel: 175 mg/m^2, 60 min IV infusion, every 3 weeks (Cycles 5-8) Epirubicin: 75 mg/m^2, IV bolus infusion, every 3 weeks (Cycles 1-4) Cyclophosphamide: 600 mg/m^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
All Cause Mortality
	TX05 (Trastuzumab)		Herceptin®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/394 (0%)		1/400 (0.3%)
Serious Adverse Events
	TX05 (Trastuzumab)		Herceptin®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/394 (2.8%)		9/400 (2.3%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/394 (0.3%)		1/400 (0.3%)
Cardiac disorders
Atrial Fibrillation	0/394 (0%)		1/400 (0.3%)
Cardiac Failure Acute	1/394 (0.3%)		0/400 (0%)
Cardiotoxicity	0/394 (0%)		1/400 (0.3%)
Myocardial Infarction	0/394 (0%)		1/400 (0.3%)
Gastrointestinal disorders
Gastrointestinal Inflammation	0/394 (0%)		1/400 (0.3%)
General disorders
Multiple Organ Dysfunction Syndrome	0/394 (0%)		1/400 (0.3%)
Hepatobiliary disorders
Drug-induced liver injury	2/394 (0.5%)		0/400 (0%)
Immune system disorders
Anaphylactic Reaction	0/394 (0%)		1/400 (0.3%)
Infections and infestations
Pneumonia	1/394 (0.3%)		1/400 (0.3%)
Urinary Tract Infection	2/394 (0.5%)		0/400 (0%)
COVID-19 Pneumonia	0/394 (0%)		1/400 (0.3%)
Injury, poisoning and procedural complications
Post Procedural Hemorrhage	0/394 (0%)		1/400 (0.3%)
Investigations
Neutrophil Count Decreased	1/394 (0.3%)		1/400 (0.3%)
Ejection Fraction Decreased	0/394 (0%)		1/400 (0.3%)
Metabolism and nutrition disorders
Diabetic Metabolic Decompensation	1/394 (0.3%)		0/400 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion	1/394 (0.3%)		0/400 (0%)
Nervous system disorders
Ischemic Stroke	0/394 (0%)		1/400 (0.3%)
Pregnancy, puerperium and perinatal conditions
Fetal Death	0/394 (0%)		1/400 (0.3%)
Renal and urinary disorders
Acute Kidney Injury	0/394 (0%)		2/400 (0.5%)
Reproductive system and breast disorders
Vaginal Hemorrhage	1/394 (0.3%)		0/400 (0%)
Vascular disorders
Thrombophlebitis	1/394 (0.3%)		0/400 (0%)
Deep Vein Thrombosis	0/394 (0%)		1/400 (0.3%)
Other (Not Including Serious) Adverse Events
	TX05 (Trastuzumab)		Herceptin®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	246/394 (62.4%)		250/400 (62.5%)
Blood and lymphatic system disorders
Anemia	26/394 (6.6%)		25/400 (6.3%)
Gastrointestinal disorders
Nausea	27/394 (6.9%)		31/400 (7.8%)
General disorders
Asthenia	30/394 (7.6%)		40/400 (10%)
Investigations
Alanine Aminotransferase Increased	27/394 (6.9%)		26/400 (6.5%)
Aspartate Aminotransferase Increased	19/394 (4.8%)		12/400 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	50/394 (12.7%)		42/400 (10.5%)
Myalgia	45/394 (11.4%)		39/400 (9.8%)
Nervous system disorders
Peripheral Sensory Neuropathy	33/394 (8.4%)		30/400 (7.5%)
Neuropathy Peripheral	16/394 (4.1%)		33/400 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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