Trial Outcomes & Findings for Trial to Compare the Safety, Efficacy and Immunogenicity of TX05 With Herceptin® in HER2+ Early Breast Cancer (NCT NCT03556358)

Last Updated: 2022-01-14

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

809 participants

Primary outcome timeframe

3-7 weeks following last dose of study treatment

Results posted on

2022-01-14

Participant Flow

A total of 809 subjects were randomized to the study. Of these, 806 subjects initiated protocol treatment.

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.

Participant milestones

Participant milestones
Measure	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 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)	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 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)
Overall Study STARTED	404	405
Overall Study Subjects Treated	401	405
Overall Study Subjects Receiving TX05 or Herceptin	394	400
Overall Study COMPLETED	393	393
Overall Study NOT COMPLETED	11	12

Reasons for withdrawal

Reasons for withdrawal
Measure	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 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)	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 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)
Overall Study Subjects Randomized that did not Treat	3	0
Overall Study Subjects who Randomized and Treated but Drop prior to Cycle 5	7	5
Overall Study Discontinued Treatment after Cycle 5 due to Adverse Event	0	1
Overall Study Discontinued Treatment after Cycle 5 due to Death	0	1
Overall Study Discontinued Treatment after Cycle 5 due to Consent Withdrawn	0	2
Overall Study Discontinued Treatment after Cycle 5 due to COVID-19	0	1
Overall Study Discontinued Treatment after Cycle 5 due to Other (Subject Decision)	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TX05 (Trastuzumab) n=394 Participants • 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)	Herceptin® n=400 Participants • 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 n=794 Participants Total of all reporting groups
Age, Continuous	54.2 years STANDARD_DEVIATION 11.80 • n=5 Participants	53.4 years STANDARD_DEVIATION 10.83 • n=7 Participants	53.8 years STANDARD_DEVIATION 11.32 • n=5 Participants
Sex: Female, Male Female	394 Participants n=5 Participants	400 Participants n=7 Participants	794 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	69 Participants n=5 Participants	71 Participants n=7 Participants	140 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	325 Participants n=5 Participants	328 Participants n=7 Participants	653 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) Asian	64 Participants n=5 Participants	72 Participants n=7 Participants	136 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	292 Participants n=5 Participants	286 Participants n=7 Participants	578 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants	27 Participants n=7 Participants	50 Participants n=5 Participants
Hormone Receptor Status Positive	253 Participants n=5 Participants	254 Participants n=7 Participants	507 Participants n=5 Participants
Hormone Receptor Status Negative	141 Participants n=5 Participants	146 Participants n=7 Participants	287 Participants n=5 Participants
ECOG Grade 0	316 Participants n=5 Participants	305 Participants n=7 Participants	621 Participants n=5 Participants
ECOG Grade 1	78 Participants n=5 Participants	95 Participants n=7 Participants	173 Participants n=5 Participants
Tumor Stage IIA	142 Participants n=5 Participants	141 Participants n=7 Participants	283 Participants n=5 Participants
Tumor Stage IIB	169 Participants n=5 Participants	173 Participants n=7 Participants	342 Participants n=5 Participants
Tumor Stage IIIA	83 Participants n=5 Participants	86 Participants n=7 Participants	169 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3-7 weeks following last dose of study treatment

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

Outcome measures

Outcome measures
Measure	TX05 (Trastuzumab) n=336 Participants • 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)	Herceptin® n=338 Participants • 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)
Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) Subjects who do not Meet pCR Criteria	172 participants	185 participants
Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) Subjects Meeting pCR Criteria	164 participants	153 participants

SECONDARY outcome

Timeframe: End of Treatment (Week 24) or Early Termination Visit

Population: 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.

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.

Outcome measures

Outcome measures
Measure	TX05 (Trastuzumab) n=394 Participants • 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)	Herceptin® n=400 Participants • 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)
Objective Response Rate (ORR)	332 Participants	340 Participants

Adverse Events

TX05 (Trastuzumab)

Serious events: 11 serious events

Other events: 246 other events

Deaths: 0 deaths

Herceptin®

Serious events: 9 serious events

Other events: 250 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	TX05 (Trastuzumab) n=394 participants at risk • 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)	Herceptin® n=400 participants at risk • 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)
Musculoskeletal and connective tissue disorders Arthralgia	12.7% 50/394 • 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). 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.	10.5% 42/400 • 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). 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.
Musculoskeletal and connective tissue disorders Myalgia	11.4% 45/394 • 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). 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.	9.8% 39/400 • 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). 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.
Nervous system disorders Peripheral Sensory Neuropathy	8.4% 33/394 • 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). 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.	7.5% 30/400 • 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). 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.
Nervous system disorders Neuropathy Peripheral	4.1% 16/394 • 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). 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.	8.2% 33/400 • 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). 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.
Gastrointestinal disorders Nausea	6.9% 27/394 • 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). 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.	7.8% 31/400 • 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). 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.
General disorders Asthenia	7.6% 30/394 • 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). 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.	10.0% 40/400 • 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). 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.
Investigations Alanine Aminotransferase Increased	6.9% 27/394 • 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). 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.	6.5% 26/400 • 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). 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.
Investigations Aspartate Aminotransferase Increased	4.8% 19/394 • 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). 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.	3.0% 12/400 • 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). 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.
Blood and lymphatic system disorders Anemia	6.6% 26/394 • 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). 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.	6.2% 25/400 • 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). 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.

Additional Information

Study Director

Tanvex

Phone: 19494838507

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER