CompletedNCT03262935TULIPUpdated Oct 19, 2023Results posted

SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer

A Phase 3 interventional study of (vic-)trastuzumab duocarmazine and Physician's choice in Metastatic Breast Cancer, sponsored by Byondis B.V.. Completed at 90 sites in 11 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-19.

Sponsored by Byondis B.V. · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 437
Allocation: Randomized
Ages: 18 Years and older
Sex: Female

Study summary

The purpose of this study is to demonstrate that SYD985 [(vic-)trastuzumab duocarmazine] is superior to physician's choice in prolonging progression free survival.

Read the detailed description

This study is designed as a randomized, active-controlled, superiority study in patients with unresectable locally advanced or metastatic HER2-positive breast cancer. The patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment.

Eligible patients will be randomly assigned (2:1) to receive SYD985 or physician's choice treatment until disease progression, unacceptable toxicity or study termination by the Sponsor. During treatment, patients will have to visit the clinical site to assess efficacy, quality of life (QoL), and safety using standardized criteria.

Conditions studied

Metastatic Breast Cancer

Browse trials for

Breast Neoplasms 12,520

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

Eligibility criteria

Main Inclusion Criteria:

Female patients with histologically-confirmed, unresectable locally advanced or metastatic breast cancer;
Patients should have had either progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment for locally advanced or metastatic disease;
HER2-positive tumor status;
Patients must have measurable or non-measurable disease that is evaluable per RECIST 1.1;
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
Estimated life expectancy > 12 weeks at randomization;
Adequate organ function and blood cell counts.

Main Exclusion Criteria:

Current or previous use of a prohibited medication as listed in the protocol;
History of infusion-related reactions and/or hypersensitivity to trastuzumab, (ado-)trastuzumab emtansine;
History of keratitis;
Severe, uncontrolled systemic disease at screening;
Left Ventricular Ejection Fraction (LVEF) \< 50%, or a history of clinically significant decrease in LVEF during previous treatment with trastuzumab or (ado-)trastuzumab emtansine;
Cardiac troponin value above the Upper Limit of Normal (ULN);
History of clinically significant cardiovascular disease;
Untreated brain metastases, symptomatic brain metastases, brain metastases requiring steroids to manage symptoms, or treatment for brain metastases within 8 weeks prior to randomization;
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 437 participants (actual)

Study arms

Experimental
(vic-)trastuzumab duocarmazine
SYD985, every 3 weeks (Q3W)
Drug: (vic-)trastuzumab duocarmazine
Active comparator
Physician's choice
1. Lap/Cap 2. T/Cap 3. T/Vino 4. T/Eri
Drug: Physician's choice

Interventions

Drug(vic-)trastuzumab duocarmazine
Intravenous SYD985, Q3W
Also known as: SYD985, Trastuzumab vc-seco-DUBA
DrugPhysician's choice
See drug label
Also known as: Lapatinib (Lap), Capecitabine (Cap), Trastuzumab (T), Vinorelbine (Vino), Eribulin (Eri)

What researchers measure

Primary outcomes

Progression Free Survival
Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by central assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred earlier.
Time frame: baseline until primary analysis data cut-off date of 31March2021

Secondary outcomes

Overall Survival
Overall survival is defined as the time from date of randomization to death due to any cause.
Time frame: baseline until final Overall Survival analysis data cut-off date of 30June2022
Objective Response Rate
Objective Response Rate is defined as the proportion of patients with a centrally assessed best overall response of complete response or partial response according to RECIST v1.1.
Time frame: baseline until primary analysis data cut-off date of 31March2021
Investigator Assessed Progression Free Survival
Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier.
Time frame: baseline until primary analysis data cut-off date of 31March2021
Patient Reported Outcomes for Health Related Quality of Life
Change in the global health status/Quality of Life (QoL) scale score of the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 from baseline (cycle 1). The raw score (1 to 7) has been transformed to a score ranging from 0 to 100. A higher score means a better outcome: hence a positive change from baseline means an improvement in global health status/Quality of Life and a negative change from baseline means a worsening of global health status/Quality of Life.
Time frame: baseline until primary analysis data cut-off date of 31March2021

Results

Posted Oct 19, 2023

Participant flow

A total of 751 participants were screened, out of which, 437 participants were randomized into the study.

Participant flow — Overall Study
Milestone	(Vic-)Trastuzumab Duocarmazine	Physician's Choice
Started	291	146
Completed	0	0
Not completed	291	146
Withdrew: Withdrawal by subject	6	7
Withdrew: End of follow up by sponsor	90	41
Withdrew: Death	181	94
Withdrew: Lost to follow-up	9	4
Withdrew: Other reason	5	0

Outcome measures

PrimaryProgression Free Survival

Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by central assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred earlier.

Time frame:: baseline until primary analysis data cut-off date of 31March2021
Reported as:: Median · months

Progression Free Survival
months	(Vic-)Trastuzumab Duocarmazine	Physician's Choice
Progression Free Survival	7.0 (5.4 to 7.2)	4.9 (4.0 to 5.5)

Statistical analysis

(Vic-)Trastuzumab Duocarmazine vs Physician's Choice · Log Rank · p = =0.002 (P-value from stratified log-rank test for median estimate of PFS: stratified according to the randomization stratification factors.) · Hazard ratio (hr): 0.6401 · 95% CI 0.4885 to 0.8389

SecondaryOverall Survival

Overall survival is defined as the time from date of randomization to death due to any cause.

Time frame:: baseline until final Overall Survival analysis data cut-off date of 30June2022
Reported as:: Median · months

Overall Survival
months	(Vic-)Trastuzumab Duocarmazine	Physician's Choice
Overall Survival	21.0 (18.1 to 25.0)	19.5 (14.2 to 23.1)

Statistical analysis

(Vic-)Trastuzumab Duocarmazine vs Physician's Choice · Log Rank · p = =0.236 (P-value from stratified log-rank test for Kaplan-Meier estimate of median OS: stratified according to the randomization stratification factors.) · Hazard ratio (hr): 0.868 · 95% CI 0.676 to 1.1145

SecondaryObjective Response Rate

Objective Response Rate is defined as the proportion of patients with a centrally assessed best overall response of complete response or partial response according to RECIST v1.1.

Time frame:: baseline until primary analysis data cut-off date of 31March2021
Reported as:: Number · percentage of patients

Objective Response Rate
percentage of patients	(Vic-)Trastuzumab Duocarmazine	Physician's Choice
Objective Response Rate	27.8 (22.3 to 33.7)	29.5 (21.6 to 38.4)

Statistical analysis

(Vic-)Trastuzumab Duocarmazine vs Physician's Choice · Cochran-Mantel-Haenszel · p = =0.732 (P-value from Cochran-Mantel-Haenszel test including the randomization stratification factors.)

SecondaryInvestigator Assessed Progression Free Survival

Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier.

Time frame:: baseline until primary analysis data cut-off date of 31March2021
Reported as:: Median · months

Investigator Assessed Progression Free Survival
months	(Vic-)Trastuzumab Duocarmazine	Physician's Choice
Investigator Assessed Progression Free Survival	6.9 (6.0 to 7.2)	4.6 (4.0 to 5.6)

Statistical analysis

(Vic-)Trastuzumab Duocarmazine vs Physician's Choice · Log Rank · p = <0.001 (P-value from stratified log-rank test for median estimate of PFS: stratified according to the randomization stratification factors.) · Hazard ratio (hr): 0.5995 · 95% CI 0.4666 to 0.7703

SecondaryPatient Reported Outcomes for Health Related Quality of Life

Change in the global health status/Quality of Life (QoL) scale score of the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 from baseline (cycle 1). The raw score (1 to 7) has been transformed to a score ranging from 0 to 100. A higher score means a better outcome: hence a positive change from baseline means an improvement in global health status/Quality of Life and a negative change from baseline means a worsening of global health status/Quality of Life.

Time frame:: baseline until primary analysis data cut-off date of 31March2021
Reported as:: Least squares mean · scores on a scale

Patient Reported Outcomes for Health Related Quality of Life
scores on a scale	(Vic-)Trastuzumab Duocarmazine	Physician's Choice
Cycle 2	0.17 (-2.70 to 3.04)	-3.88 (-7.79 to 0.03)
Cycle 3	-1.88 (-4.83 to 1.07)	-2.99 (-7.00 to 1.02)
Cycle 4	-2.48 (-5.46 to 0.50)	-9.01 (-13.23 to -4.80)
Cycle 5	-2.51 (-5.69 to 0.67)	-5.77 (-10.34 to -1.21)
Cycle 7	-5.65 (-9.19 to -2.10)	-6.75 (-11.92 to -1.58)
Cycle 9	-8.14 (-12.27 to -4.02)	-11.25 (-17.41 to -5.09)
Cycle 11	-10.70 (-15.66 to -5.75)	-10.38 (-18.08 to -2.69)
Cycle 13	-13.40 (-20.31 to -6.48)	-12.89 (-21.33 to -4.45)
Cycle 15	-11.90 (-20.41 to -3.39)	-14.12 (-23.91 to -4.33)
Cycle 17	-4.31 (-14.48 to 5.86)	-0.71 (-13.26 to 11.83)
Cycle 19	-5.45 (-21.05 to 10.16)	1.66 (-13.84 to 17.16)
Cycle 21	11.68 (-9.76 to 33.12)	-11.23 (-26.16 to 3.71)
Cycle 23	5.30 (-26.04 to 36.65)	-7.00 (-29.18 to 15.17)
Cycle 25	18.76 (-14.63 to 52.16)	-11.48 (-42.96 to 19.99)
Cycle 27	0.49 (-33.40 to 34.37)	-5.41 (-38.83 to 28.02)
Cycle 29	—	-6.54 (-40.45 to 27.37)
Cycle 33	—	-7.11 (-41.14 to 26.92)
Cycle 35	—	-15.73 (-49.79 to 18.33)

Statistical analysis

(Vic-)Trastuzumab Duocarmazine vs Physician's Choice · MMRM · p = 0.473

Adverse events

Collected over Adverse Events were collected from signing of the ICF up to the treatment discontinuation visit. The safety data reported here is based on data collected up to the data cut off date of 31 March 2021.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
(Vic-)Trastuzumab Duocarmazine	181/288 (62.8%)	53/288 (18.4%)	278/288 (96.5%)
Physician's Choice	94/137 (68.6%)	12/137 (8.8%)	132/137 (96.4%)

Most frequent serious events

Showing 10 of 67

Most frequent serious events
Event	(Vic-)Trastuzumab Duocarmazine	Physician's Choice
PneumonitisRespiratory, thoracic and mediastinal disorders	7/288	0/137
PneumothoraxRespiratory, thoracic and mediastinal disorders	0/288	3/137
PneumoniaInfections and infestations	3/288	1/137
PyrexiaGeneral disorders	1/288	1/137
General physical health deteriorationGeneral disorders	0/288	1/137
Pulmonary embolismRespiratory, thoracic and mediastinal disorders	1/288	1/137
Upper respiratory tract infectionRespiratory, thoracic and mediastinal disorders	1/288	1/137
Febrile neutropeniaBlood and lymphatic system disorders	0/288	1/137
DiarrhoeaGastrointestinal disorders	1/288	1/137
VomitingGastrointestinal disorders	0/288	1/137

Most frequent other events

Showing 10 of 55

Most frequent other events
Event	(Vic-)Trastuzumab Duocarmazine	Physician's Choice
ConjunctivitisEye disorders	110/288	3/137
KeratitisEye disorders	110/288	11/137
DiarrhoeaGastrointestinal disorders	60/288	49/137
FatigueGeneral disorders	96/288	41/137
NauseaGastrointestinal disorders	73/288	43/137
Dry eyeEye disorders	87/288	14/137
NeutropeniaBlood and lymphatic system disorders	31/288	33/137
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders	2/288	32/137
AlopeciaSkin and subcutaneous tissue disorders	62/288	16/137
Decreased appetiteMetabolism and nutrition disorders	61/288	15/137

Baseline characteristics

Age, Continuous
Age, Continuous(years)	(Vic-)Trastuzumab Duocarmazine	Physician's Choice	Total
Mean	55.9 ± 11.2	57.3 ± 10.97	56.4 ± 11.13

Sex: Female, Male
Sex: Female, Male(Participants)	(Vic-)Trastuzumab Duocarmazine	Physician's Choice	Total
Female	291	146	437
Male	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	(Vic-)Trastuzumab Duocarmazine	Physician's Choice	Total
Hispanic or Latino	11	8	19
Not Hispanic or Latino	225	103	328
Unknown or Not Reported	55	35	90

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	(Vic-)Trastuzumab Duocarmazine	Physician's Choice	Total
American Indian or Alaska Native	1	0	1
Asian	29	17	46
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	4	2	6
White	202	95	297
More than one race	0	0	0
Unknown or Not Reported	55	32	87

Region of Enrollment
Region of Enrollment(participants)	(Vic-)Trastuzumab Duocarmazine	Physician's Choice	Total
Canada	15	9	24
Netherlands	3	0	3
Sweden	4	4	8
Singapore	20	15	35
Belgium	25	15	40
United States	34	19	53
Denmark	7	3	10
Italy	50	20	70
United Kingdom	43	16	59
France	46	22	68
Spain	44	23	67

BMI
BMI(kg/m2)	(Vic-)Trastuzumab Duocarmazine	Physician's Choice	Total
Mean	25.14 ± 5.0	25.54 ± 6.1	25.28 ± 5.4

Childbearing potential
Childbearing potential(Participants)	(Vic-)Trastuzumab Duocarmazine	Physician's Choice	Total
Yes	64	32	96
No - postmenopausal	204	105	309
No - surgically sterilized	23	9	32

Study locations

90 sites

Southern Cancer Center
Mobile, Alabama 36608, United States
Arizona Clinical Research Center
Tucson, Arizona 85715, United States
Moores UCSD Cancer Center
San Diego, California 92093, United States
Woodlands Medical Specialists
Pensacola, Florida 32503, United States
Rush University Medical Center
Chicago, Illinois 60612, United States
Cancer Center of Kansas
Wichita, Kansas 67214, United States
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland 21144, United States
Greater Baltimore Medical Center
Baltimore, Maryland 21204, United States
Henry Ford Hospital
Detroit, Michigan 48202, United States
Saint Luke's Hospital of Kansas City
Kansas City, Missouri 64111, United States
FirstHealth Outpatient Cancer Center
Pinehurst, North Carolina 28374, United States
Toledo Clinic Cancer Center
Toledo, Ohio 43623, United States
Northwest Cancer Specialists
Portland, Oregon 97213, United States
Magee-Womens Hospital of UPMS
Pittsburgh, Pennsylvania 15213, United States
Texas Oncology PA (Texas Oncology-Dallas Presbyterian Hospital)
Dallas, Texas 75231, United States
Texas Oncology- Baylor Charles A. Sammor
Dallas, Texas 75246, United States
Texas Oncology - Denton South
Denton, Texas 76210, United States
Texas Oncology-Memorial City
Houston, Texas 77024, United States
Baylor College of Medicine
Houston, Texas 77030-34011, United States
Texas Oncology-San Antonio Northeast
San Antonio, Texas 78217, United States
Texas Oncology-Tyler
Tyler, Texas 75702, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia 22031, United States
Virginia Oncology Associates
Norfolk, Virginia 23502, United States
Institut Jules Bordet
Brussel, 1000, Belgium
Cliniques Universitaires Saint-Luc
Bruxelles, 1200, Belgium
University Hospital Antwerp
Edegem, 2650, Belgium
UZ Gent
Gent, 9000, Belgium
AZ Groeninge
Kortrijk, 8500, Belgium
UZ Leuven - campus Gasthuisberg
Leuven, 3000, Belgium
CHU Liege
Liege, B-4000, Belgium
Cross Cancer Institute
Edmonton, T6G 1Z2, Canada
BC Cancer Agency Centre for the Southern Interior
Kelowna, V1Y 5L3, Canada
McGill University Health Centre
Montreal, H4A 3JI, Canada
The Ottawa Hospital Cancer Center
Ottawa, K1H 8L6, Canada
Sealand University Hospital
Naestved, 4700, Denmark
Odense University Hospital
Odense, DK-5000, Denmark
Sønderborg sygehus
Sønderborg, 6400, Denmark
Institut de Cancerologie de l'ouest
Angers, 49055, France
Institut Bergonie
Bordeaux, 33076, France
CH Fleyrait
Bourg-en-Bresse, 01012, France
Centre Hospitalier Lyon Sud
Corbeil-Essonnes, 91100, France
Centre Georges francois leclerc
Dijon, 21079, France
Oscar Lambret
Lille, 59020, France
CHR Metz-Thionville
Metz, 57085, France
Hopital Prive du Confluent
Nantes, 44277, France
Hopital Saint Louis
Paris, 75475, France
Centre Hospitalier Lyon Sud
Pierre-Benite, 69310, France
Centre Henri Becquere
Rouen, 76038, France
Centre Paul Strauss
Strasbourg, 67065, France
IRCCS Istituto Oncologico
Bari, 70124, Italy
Policlinico S.Orsola-Malpighi
Bologna, 40183, Italy
Azienda Ospedaliera Garibaldi- Nesima
Catania, 95123, Italy
Azienda Ospedaliero - Universitaria Careggi
Firenze, 50134, Italy
IRCCS Ospedale San Raffaele
Milano, 20132, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, 20133, Italy
Istituto Europeo di Oncologia
Milano, 20141, Italy
University Hospital of Modena
Modena, 41124, Italy
Ospedale San Gerardo-Asst Monza
Monza, 20900, Italy
Istituto Oncologico Veneto Irccs
Padova, 35128, Italy
Nuovo Ospedale Santo Stefano
Prato, 59100, Italy
Istituto Nazionale dei Tumori Regina Elena
Roma, 144, Italy
Azienda Ospedaliera Sant'Andrea
Roma, 189, Italy
Casa Sollievo Della Sofferenza
San Giovanni Rotondo, 71013, Italy
Radboud University Medical Center
Nijmegen, Gelderland 6251 GA, Netherlands
VU Medical Center
Amsterdam, Noord-Holland 1081 HV, Netherlands
University Medical Center Groningen
Groningen, 9700 VB, Netherlands
National University Cancer Institute
Singapore, 119228, Singapore
National Cancer Centre Singapore
Singapore, 169610, Singapore
Hospital General Universitario de Alicante
Alicante, 3010, Spain
Hospital Quironsalud
Barcelona, 08023, Spain
Hospital Universitari Vall d'Hebron Vall d' Hebron Institute of Oncology (VHIO)
Barcelona, 8035, Spain
Hospital Clinic de Barcelona
Barcelona, 8036, Spain
Institut Catala D'oncologia
Barcelona, 8908, Spain
Hospital Arnau de Vilanova
Lleida, 21598, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28009, Spain
IOB del Hospital Ruber Internacional
Madrid, 28045, Spain
Hospital HM Universitario Sanchinarro
Madrid, 28050, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009, Spain
Gävle Sjukhus Onkologkliniken
Gävle, 80187, Sweden
Sahlgrenska University Hospital
Göteborg, 413 45, Sweden
Karolina University Hospital
Stockholm, S-171 76, Sweden
Akademiska Hospital
Uppsala, 78551, Sweden
The Clatterbridge Cancer Centre NHS Foundation Trust
Bebington, CH63 4JY, United Kingdom
Velindre Cancer Centre VCC
Cardiff, CF14 2TL, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ, United Kingdom
SCRI UK
London, W1G 6AD, United Kingdom
The Christie NHS Foundation
Manchester, M20 4GJ, United Kingdom
Oxford University NHS hospital
Oxford, OX3 7LE, United Kingdom

References and documents

Study documents

Study protocol · Jan 18, 2021
Statistical analysis plan · Apr 29, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03262935
Lead sponsor: Byondis B.V.
Responsible party: Sponsor
First posted: Aug 25, 2017
Start date: Dec 15, 2017
Primary completion: Mar 31, 2021
Completion: Jun 30, 2022
Results posted: Oct 19, 2023
Last update: Oct 19, 2023

Study contacts

Evelyn van den Tweel, PhD

study director · Byondis B.V., The Netherlands

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

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