SYS6010 EGFR-Targeted ADC
SYS6010-021 (NCT07406542) is a Phase III randomized study in China comparing SYS6010, an investigational EGFR-targeted antibody-drug conjugate, against standard chemotherapy in adults with HER2-negative, EGFR-positive recurrent or metastatic breast cancer who have received prior chemotherapy. The trial plans to enroll approximately 400 patients across multiple centers. CancerFax helps patients and families understand whether this trial may be relevant and coordinate pre-screening review with the trial centers.
About This Clinical Trial
Patients with HER2-negative metastatic breast cancer face a difficult treatment landscape once first- and second-line chemotherapy stop working. This includes both hormone-receptor positive, HER2-negative breast cancer and triple-negative breast cancer. In these later lines, available options are limited, response rates are generally lower, and many patients and families are actively looking for clinical studies that may offer something beyond what standard care currently provides.
SYS6010-021 (NCT07406542) is a randomized, open-label, multicenter Phase III study being conducted in China by CSPC Megalith Biopharmaceutical Co., Ltd., part of CSPC Pharmaceutical Group. It compares SYS6010, an investigational EGFR-targeted antibody-drug conjugate (ADC), head-to-head against the investigator's choice of standard single-agent chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in patients with HER2-negative, centrally confirmed EGFR-positive breast cancer who have already received one or two prior lines of chemotherapy for advanced disease. Approximately 400 patients are randomized 1:1 between the two arms.
EGFR is expressed in a significant proportion of HER2-negative breast cancers β particularly in triple-negative disease, where expression rates have been reported in the range of 50 to 70 percent, and to a lesser extent in HR-positive, HER2-negative disease. Despite this, no EGFR-targeted therapy has been routinely approved specifically for this breast cancer population. SYS6010 is designed to exploit EGFR expression by delivering a potent topoisomerase I inhibitor payload (JS-1, a camptothecin-derived agent) directly into EGFR-expressing tumor cells, using a cleavable GGFG linker and a drug-to-antibody ratio of approximately 8. A bystander effect may allow the payload to affect neighboring tumor cells even when EGFR expression is uneven.
Preliminary data from the earlier SYS6010-008 Phase II study, reported as of early 2026, showed a confirmed objective response rate of 37% and disease control in approximately 78% of heavily pre-treated patients at the 3.6 mg/kg every-two-weeks dose. Updated subgroup data suggested response rates of 40% in HR-positive, HER2-negative patients and 54.3% in triple-negative patients, though these are early, non-randomized results and require confirmation through the Phase III trial. The primary endpoint of SYS6010-021 is progression-free survival (PFS) by blinded independent central review (BICR).
The study aims to determine whether SYS6010 extends progression-free survival compared with standard chemotherapy in patients with HER2-negative, EGFR-positive advanced breast cancer after prior chemotherapy.
Trial at a Glance
A quick factual summary of the key features of this trial. This is not an eligibility assessment for any individual patient.
Final eligibility is determined only by the trial investigators after reviewing complete medical records.
Treatment Being Studied
SYS6010 is an antibody-drug conjugate (ADC) that targets EGFR, a protein found on the surface of many breast cancer cells, particularly in HER2-negative and triple-negative subtypes. The concept behind an ADC is straightforward: a targeting antibody is chemically linked to a cancer-killing drug. The antibody homes in on cancer cells expressing the target protein, and once attached, the cell pulls the entire ADC inside β at which point the payload is released to damage or kill the tumor cell.
In this Phase III study, SYS6010 is compared directly against one of four standard chemotherapy drugs that the treating oncologist selects (eribulin, capecitabine, gemcitabine, or vinorelbine). Patients are randomized 1:1 and do not choose which arm they are in. The question the study is asking is whether the targeted ADC controls the cancer for longer than conventional chemotherapy.
How SYS6010 works (in plain terms)
SYS6010's antibody binds to EGFR on the tumor cell surface. The cell then internalizes the ADC. Inside the cell, lysosomal enzymes cut the cleavable GGFG linker and release JS-1, a camptothecin-derived topoisomerase I inhibitor, which damages the cell's DNA replication machinery and triggers cell death. The released payload can also diffuse into neighboring tumor cells even when EGFR expression is not uniform β this is known as a bystander effect. SYS6010 is given at 3.6 mg/kg with a drug-to-antibody ratio of approximately 8, administered by intravenous infusion every two weeks.
Confirmation of HER2-negative status, central laboratory EGFR testing, review of prior treatment lines, imaging for measurable disease, performance status, and organ function tests.
Eligible patients are randomly assigned to either the SYS6010 arm or the investigator-selected chemotherapy arm. The patient does not choose the arm.
SYS6010 arm: 3.6 mg/kg IV infusion every 14 days (day 1 of each cycle). Control arm: investigator's choice of standard chemotherapy per protocol schedule.
Regular blood counts, liver and kidney function, and monitoring for lung symptoms, cardiac function, and gastrointestinal effects throughout treatment cycles.
Tumor imaging approximately every 6 weeks for the first 48 weeks, then every 12 weeks, to assess progression-free survival and objective response per RECIST v1.1.
Continued follow-up for overall survival, quality of life, pharmacokinetics, and immunogenicity as defined by the study protocol through approximately 2030.
SYS6010 is not yet an approved treatment. It is being evaluated in a Phase III trial, and its benefits and full safety profile in this population are still being established.
Who This Trial May Be For
This trial may be relevant for certain adults with HER2-negative, EGFR-positive metastatic breast cancer who have already received chemotherapy. The cards below describe the general profile. Actual eligibility is confirmed by the trial team only after reviewing complete medical records.
Adults with histologically confirmed unresectable recurrent or metastatic breast cancer that is HER2-negative and confirmed EGFR-positive by central laboratory testing (IHC β₯1+ in β₯1% of tumor cells). Both triple-negative and HR-positive, HER2-negative subtypes are eligible.
Patients who have received one or two prior lines of systemic chemotherapy for unresectable advanced or metastatic breast cancer. HR-positive patients must also have received at least one endocrine treatment for advanced disease and be considered unlikely to benefit further from endocrine therapy.
Patients must not have previously received a topoisomerase I inhibitor (including topoisomerase I payload-containing ADCs) or any EGFR-targeted ADC or EGFR-targeted monoclonal antibody. This is a firm exclusion.
ECOG performance status of 0 or 1, expected survival of at least 3 months, and adequate hematologic, liver, kidney, and cardiac function within protocol-defined thresholds. Age 18 to 75 years.
At least one measurable lesion by CT or MRI per RECIST v1.1. No current or prior steroid-treated interstitial lung disease or non-infectious pneumonitis, and no imaging findings where ILD cannot be excluded.
The trial runs at multiple centers in China. International patients need translated medical records, remote case pre-review, a valid visa, and a stay near the treating center. CancerFax helps coordinate these steps.
Eligibility Criteria
The criteria below are sourced from the ClinicalTrials.gov registry for NCT07406542. Meeting some of these points does not confirm eligibility. The full protocol may have additional criteria, and only the trial investigators can make a final determination after reviewing complete medical records.
check_circleInclusion Criteria β May Be Eligible
- βAge 18 to 75 years inclusive; no gender restrictions
- βHistopathologically confirmed breast cancer at an unresectable recurrent or metastatic stage: must be HER2-negative AND EGFR-positive expression confirmed by central laboratory (IHC β₯1+ in β₯1% of tumor cells)
- βMust have received 1 to 2 prior lines of systemic chemotherapy for unresectable advanced or metastatic disease
- βHR-positive patients: must have received at least one endocrine treatment for advanced disease and be considered unlikely to benefit from further endocrine therapy
- βAt least one measurable lesion by CT or MRI per RECIST v1.1 (brain metastases evaluated as non-target lesions only; skin lesions only β ineligible)
- βECOG performance status of 0 or 1
- βExpected survival of at least 3 months
- βAdequate major organ function within 7 days before first study drug administration
- βEffective contraception required from consent signing until protocol-specified time after last dose; women of childbearing potential must have a negative serum pregnancy test within 7 days before first dose; women must not be lactating
- βVoluntary written informed consent
cancelExclusion Criteria β May Not Be Eligible
- ΓCancerous meningitis, spinal cord compression, or active (untreated/symptomatic) central nervous system metastases β except previously treated brain metastases stable for β₯1 month with corticosteroids and anticonvulsants discontinued for >2 weeks
- ΓPoorly controlled pleural effusion, pericardial effusion, or ascites requiring frequent drainage or recent intervention within 2 weeks
- ΓHistory of other malignancy within 3 years (except cured skin BCC/SCC, superficial bladder cancer, prostate CIS, papillary thyroid carcinoma, cervical CIS)
- ΓPrior treatment with topoisomerase I inhibitors (including topoisomerase I payload ADCs)
- ΓPrior treatment with EGFR-targeted ADCs or EGFR-targeted monoclonal antibodies
- ΓKnown hypersensitivity to SYS6010 components or humanized monoclonal antibody products
- ΓUnresolved adverse events from prior therapy not recovered to β€Grade 1 (exceptions: Grade 2 alopecia, asymptomatic lab abnormalities deemed safe by investigator)
- ΓInadequate washout period for prior treatments per protocol
- ΓHistory of severe cardiovascular or cerebrovascular disease
- ΓClinically significant pulmonary impairment due to pulmonary complications
- ΓHistory of ILD/non-infectious pneumonitis requiring glucocorticoids, current ILD/pneumonitis, or inability to exclude ILD on screening imaging
- ΓActive inflammatory bowel disease, GI obstruction, active peptic ulcer, recent GI bleeding (within 4 weeks), perforation, or severe GI conditions
- ΓSevere infection within 4 weeks before first dose (bacteremia, severe pneumonia, active tuberculosis, or requiring oral/IV antibiotics/antifungals/antivirals within 2 weeks before first dose β excluding prophylaxis)
- ΓUncontrolled diabetes: fasting glucose β₯10 mmol/L and/or HbA1c β₯8%
- ΓActive hepatitis B, active hepatitis C, active syphilis, or HIV/AIDS
- ΓOther conditions the investigator considers unsuitable for trial participation
Criteria here are illustrative. The trial protocol has its own detailed list. CancerFax can help organize records for review, but only the trial center can confirm participation.
Medical Records and Tests Needed for Review
Good, organized records make the pre-screening process faster and more accurate. CancerFax helps families gather, translate, and structure these documents before sharing them with the trial center.
How the Trial Process May Work
Joining a Phase III randomized ADC trial involves several structured steps before treatment begins. The overview below outlines the typical path for patients, including those coming from outside China.
CancerFax organizes the medical records and shares a structured summary with the relevant trial center for a preliminary eligibility assessment.
The trial requires central laboratory confirmation of EGFR positivity and HER2-negative status. Archived tumor tissue (β₯11 unstained slides preferred) or a fresh biopsy may be needed.
Confirmatory blood tests, imaging, and organ function assessments at the trial center in China to verify eligibility per protocol.
The patient and family receive a full explanation of the study design, randomization, risks, benefits, and rights before signing informed consent.
Patients are randomized 1:1 to SYS6010 IV infusion (every 2 weeks) or investigator-selected standard chemotherapy. Treatment continues until progression or per protocol.
Regular blood work, imaging every 6 weeks initially, and longer-term follow-up for survival, quality of life, and safety outcomes through approximately 2030.
Potential Benefits
Joining a Phase III trial can offer access to a therapy not yet available outside the study, along with close specialist monitoring. These are real possibilities, not guarantees, and should be weighed honestly with the treating team.
SYS6010 is an investigational EGFR-targeted ADC not available outside of clinical studies. Phase II data showed encouraging early activity in this population.
As a randomized trial, patients receive either SYS6010 or an established standard chemotherapy β both given under careful specialist supervision.
Patients are enrolled based on confirmed EGFR expression, increasing the chance that the drug's mechanism is relevant to the individual tumor.
Phase III protocols involve more frequent imaging, blood monitoring, and safety assessments than routine oncology care.
The study formally tracks quality of life using validated breast cancer-specific questionnaires (EORTC QLQ-C30 and QLQ-BR42).
Participation helps generate the evidence needed to evaluate SYS6010 as a potential new option for EGFR-positive, HER2-negative breast cancer globally.
Randomization means the patient may receive standard chemotherapy rather than SYS6010. There is no guarantee of benefit in either arm. Realistic expectations should be discussed thoroughly with the treating oncologist.
Risks and Side Effects
SYS6010 is an ADC with a topoisomerase I inhibitor payload (JS-1, camptothecin-derived). Its expected risk profile reflects that drug class. Specific incidence rates in this population are still being established in the Phase III trial.
ADCs with topoisomerase I inhibitor payloads (such as deruxtecan-type agents) carry a known risk of interstitial lung disease or non-infectious pneumonitis, which can be serious. Patients with any prior ILD history are excluded. New cough, breathlessness, or fever during treatment must be reported promptly. Incidence specific to SYS6010 is still being defined.
The Phase II study reported anaemia (69%), reduced white blood cell count (63.8%), and reduced neutrophil count (55.2%) as the most common effects. Grade β₯3 treatment-related events occurred in approximately 53% of patients. Regular blood count monitoring is required throughout treatment.
Nausea (41.4%), vomiting (19%), oral mucositis (20.7%), and reduced appetite (29.3%) were reported in early Phase II data. These are generally manageable with supportive care and dose adjustments.
Fatigue/weakness (43.1%) and hair loss (24.1%) were commonly observed in the Phase II study. These are typical effects of this class of therapy.
Elevated ALT was observed in approximately 26% of patients in early study data. Liver function is monitored throughout the study.
As with any monoclonal antibody-based therapy, reactions can occur during or shortly after intravenous infusion. The trial team monitors patients closely during and after each infusion.
SYS6010 is investigational. Long-term effects and the full safety profile in the Phase III population are still being characterized. No treatment-related deaths were observed in early Phase II data, but the randomized study will provide a more complete picture.
Randomization means the patient may receive chemotherapy, not SYS6010. Travel to China, time away from home, and the possibility of trial discontinuation should all be factored into the family's planning and discussed with the treating oncologist.
Trial Location and Hospital Information
SYS6010-021 is a multicenter study running at sites across China. The lead institution is Tianjin Breast Cancer Prevention and Treatment Center, Tianjin, China. β VERIFY: The complete list of participating sites has not yet been publicly confirmed. Patients must be evaluated at a participating trial center, and open sites should be confirmed before any travel.
International patients typically need translated medical records, a remote case review by the trial center, central EGFR and HER2 testing, a valid Chinese visa, accommodation near the hospital, and ongoing on-the-ground support. CancerFax helps organize records, communicate with the centers, and coordinate travel, translation, and admission logistics.
Costs, Trial Coverage, and Patient Expenses
According to the internal study documentation, the sponsor has purchased clinical trial insurance and will cover the investigational drug and protocol-required medical examinations. Patients may also receive modest allowances for travel, blood draws, and tissue provision. Final confirmation of all coverage must come from the trial center in writing.
CancerFax helps families understand the expected cost categories and what may be covered. Final confirmation must come from the trial center in writing before any arrangements are made.
Standard Treatment vs Clinical Trial
This trial places patients into one of two arms by randomization β SYS6010 or standard chemotherapy. The table below outlines the general differences between trial participation and continuing on standard treatment outside the study.
How CancerFax Helps Patients Explore This Trial
CancerFax is a specialist cancer access and patient-navigation platform. For complex options like randomized Phase III trials in China involving central biomarker testing and international travel, we help families get organized, communicate clearly with trial centers, and understand each step β without overpromising.
We organize and structure diagnosis, pathology, HER2/EGFR IHC, imaging, and full treatment history records for clear, efficient review by the trial team.
We help check how the inclusion and exclusion criteria may apply to the specific patient and identify any documentation gaps or additional testing needed.
We communicate with the relevant trial centers in China on the family's behalf and relay their questions, requirements, and timelines.
We support visa guidance, travel planning, accommodation near the hospital, and admission coordination for the pre-screening visit and ongoing treatment stays.
We help families understand this trial in context β including approved alternatives, other relevant studies, and what to discuss with their local oncologist.
We stay alongside the family from the first record review through follow-up, with translation support and clear communication at every step.
CancerFax does not guarantee trial enrollment, treatment response, or outcome. Our role is to help patients access accurate information and appropriate pathways.
Questions to Ask Before Considering This Trial
These questions can help patients and families have a clearer, more informed discussion with their oncologist and the trial team before making any decisions.
Frequently Asked Questions
Want to Know Whether This Trial May Be Relevant?
Share the medical reports and CancerFax will help review the case, organize documents, and coordinate with the relevant trial centers in China β including pre-screening before the study opens.
The information on this page is for educational and patient-navigation purposes only. It does not replace medical advice, diagnosis, or treatment from a qualified physician. Clinical trial eligibility, enrollment, treatment decisions, and costs are determined only by the trial investigators, hospital, sponsor, and applicable regulations. CancerFax helps patients and families understand options and coordinate case review where appropriate, but does not guarantee trial acceptance, treatment response, or clinical outcome. All clinical decisions must be made in consultation with a qualified, licensed physician with access to the patient's complete medical information.
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Β© CancerFax Β· Specialist cancer access and patient-navigation platform. CancerFax is not a medical institution, hospital, or clinical trial sponsor. Trial details may change; always confirm current eligibility, status, and costs directly with the trial center.