SYD985 + Paclitaxel for Breast Cancer

No longer recruiting at 23 trial locations

Overseen By Smita Asare

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: QuantumLeap Healthcare Collaborative

Must be taking: Taxane, Trastuzumab

Must not be taking: Anthracyclines

Disqualifiers: Cardiovascular disease, Diabetes, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 985

Duration: up to 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment that combines Vic-trastuzumab duocarmazine (SYD985, a type of targeted therapy) with paclitaxel, a common chemotherapy drug. The goal is to assess the safety and effectiveness of this combination for individuals with certain advanced cancers that are HER2-positive or HER2-low, such as breast cancer and gastroesophageal adenocarcinoma. Suitable candidates have advanced HER2-positive or HER2-low breast cancer and have already tried other treatments without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires a 'washout period' (time without taking certain medications) for some treatments before starting the study. Specifically, you must stop chemotherapy or investigational agents for 3 weeks, mitomycin C and nitrosoureas for 6 weeks, radiotherapy for 4 weeks, targeted therapy and endocrine therapy for 2 weeks, and monoclonal antibodies and immunotherapy for 4 weeks. Please consult with the study team for guidance on your specific medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that vic-trastuzumab duocarmazine (SYD985) is generally well-tolerated by people with breast cancer. In earlier studies, patients who used SYD985 experienced promising results, even after trying other treatments. Common side effects included tiredness, nausea, and low blood cell counts, but most patients managed these effectively.

Paclitaxel, a chemotherapy drug used for many years, is usually well-tolerated but can cause side effects such as hair loss, numbness in the hands and feet, and low blood counts.

In summary, while both treatments can have side effects, they are generally manageable, and many patients handle them well. It is important to consult a healthcare provider to understand what these findings mean personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about vic-trastuzumab duocarmazine (SYD985) because it represents a novel approach in targeting HER2-positive and HER2-low breast cancers. Unlike traditional treatments that might focus solely on blocking HER2 receptors, SYD985 is an antibody-drug conjugate (ADC) that combines an antibody targeting HER2 with a powerful chemotherapy drug. This dual-action allows the treatment to deliver chemotherapy directly to cancer cells, potentially increasing effectiveness while minimizing harm to healthy cells. This targeted delivery could lead to better outcomes for patients with fewer side effects than standard chemotherapy.

What evidence suggests that Vic-trastuzumab duocarmazine (SYD985) might be an effective treatment for HER2-positive or HER2-low breast cancer?

Research has shown that vic-trastuzumab duocarmazine (SYD985), administered in this trial with paclitaxel, may effectively treat breast cancer. Studies have found that SYD985 helps patients live longer without disease progression compared to standard treatments. It has shown positive results in patients with HER2-positive and HER2-low tumors, even for those who have undergone multiple treatments. This treatment uses an antibody to target cancer cells and deliver a chemotherapy drug directly to them. Overall, SYD985 could offer a new option for patients with difficult-to-treat breast cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Paula R Pohlmann, MD, MSc, PhD

Principal Investigator

M.D. Anderson Cancer Center

Anthony Elias, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Inclusion Criteria

Signed informed consent and for collection of archival FFPE blocks (freshly cut 14 unstained tumor slides would be acceptable) obtained prior to any study specific assessments and procedures.

ER, PgR and HER2 measurements should be performed according to institutional guidelines, in a CLIA-approved setting, when indicated. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines2-4 published in 2017 for Gastroesophageal Adenocarcinoma, and in 2018 for breast cancer. For other histologic types, HER2 assessment will follow local institutional criteria. Patients with breast cancer and equivocal HER2 in situ hybridization results according to current ASCO/CAP guidelines are eligible..

HER2 LOW: breast (irrespective of HR status)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly paclitaxel and tri-weekly trastuzumab duocarmazine (SYD985) infusions

up to 12 months

Weekly visits for paclitaxel, tri-weekly visits for SYD985

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vic-trastuzumab duocarmazine (SYD985)

How Is the Trial Designed?

Group I: Vic-trastuzumab duocarmazine (SYD985) + paclitaxel Experimental Treatment 1 Intervention

Single-arm, phase I trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel. The study contains 2 cohorts. Cohort A is the de-escalation cohort. Patients with certain HER-positive advanced solid tumors or HER2-low breast cancer will be enrolled in this cohort. Cohort B is the expansion cohort, in which only patients with HER2-positive or HER2-low breast cancer can be enrolled. Treatment will be administered on an outpatient basis.

Who Is Running the Clinical Trial?

QuantumLeap Healthcare Collaborative

Lead Sponsor

Trials

6

Recruited

7,000+

Byondis B.V.

Industry Sponsor

Trials

10

Recruited

1,000+

Published Research Related to This Trial

T-DM1 is highly effective against HER2-positive breast cancer cell lines, including those resistant to trastuzumab and lapatinib, demonstrating strong growth inhibition in vitro and significant tumor suppression in vivo.

The mechanism of action for T-DM1 includes inducing mitotic catastrophe, a novel finding that contributes to its effectiveness, as evidenced by increased apoptosis and abnormal cell division in treated cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo. Barok, M., Tanner, M., Köninki, K., et al.[2021]

Trastuzumab (Herceptin) has demonstrated significant antitumor activity in patients with HER-2-positive metastatic breast cancer, improving response and survival rates when combined with first-line chemotherapy.

Recent clinical trials have focused on new chemotherapy approaches for node-positive breast cancer, laying the groundwork for ongoing studies that incorporate trastuzumab into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing and planned adjuvant trials with trastuzumab. Perez, EA., Hortobagyi, GN.[2015]

Trastuzumab, a humanized monoclonal antibody targeting the HER2 receptor, has shown significant effectiveness as a single-agent treatment for metastatic breast cancer and enhances the effects of chemotherapy.

Recent studies indicate that trastuzumab is also beneficial in the adjuvant setting for early-stage breast cancer, contributing to improved disease-free and overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant treatment of breast cancer: impact of monoclonal antibody therapy directed against the HER2 receptor. Simonds, HM., Miles, D.[2019]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)04392-1/fulltext

LBA15 Primary outcome of the phase III SYD985.002 ... Treatment with SYD985 significantly improved PFS in comparison with standard PC and may provide a new treatment option for patients with pre-treated locally ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.1014

A phase I expansion cohorts study of SYD985 in heavily ... Conclusions: SYD985 shows promising efficacy in heavily pretreated patients with breast cancer, in both HER2-positive and HER2-low tumors with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10099594/

The change of paradigm in the treatment of HER2-positive ... Metastatic HER2-positive breast cancer patients are achieving better survival rates upon treatment with anti-HER2 therapies than patients with HER2-negative ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03262935

Study Details | NCT03262935 | SYD985 vs. Physician's ... The purpose of this study is to demonstrate that SYD985 [(vic-)trastuzumab duocarmazine] is superior to physician's choice in prolonging progression free ...

5. byondis.com byondis.com/investors-and-media/press-releases/byondis-announces-positive-topline-results-of-pivotal-phase-iii-tulip-study-in-patients-with-her2-positive-unresectable-locally-advanced-or-metastatic-breast-cancer

Byondis Announces Positive Topline Results of Pivotal ... “There is considerable unmet medical need in patients with HER2-positive metastatic breast cancer and [vic-]trastuzumab duocarmazine represents a promising ...

6. onclive.com onclive.com/view/trastuzumab-duocarmazine-provides-numerical-os-benefit-in-pretreated-her2-breast-cancer

Trastuzumab Duocarmazine Provides Numerical OS ... Treatment with vic-trastuzumab duocarmazine demonstrated a trend toward numerically prolonged overall survival compared with physician's choice of treatment.

7. cancernetwork.com cancernetwork.com/view/fda-issues-crl-for-trastuzumab-duocarmazine-in-advanced-her2-breast-cancer

FDA Issues CRL for Trastuzumab Duocarmazine in ... Supporting data for the BLA for trastuzumab duocarmazine in HER2-positive unresectable locally advanced or metastatic breast cancer came from ...