ISPY-P1.01:Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer

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

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for patients with specific types of advanced cancer. It aims to deliver medicine directly to cancer cells, making the treatment more effective and potentially reducing side effects.

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.

What data supports the effectiveness of the drug Vic-trastuzumab duocarmazine (SYD985)?

Research shows that trastuzumab duocarmazine, a drug similar to Vic-trastuzumab duocarmazine, has shown promising results in shrinking HER2-positive tumors, even in cases where other treatments were not effective. In a study, 33% of patients with resistant tumors experienced partial responses, indicating the drug's potential effectiveness. ^{1 2 3 4 5}

What safety data exists for Vic-trastuzumab duocarmazine (SYD985)?

In early trials, Vic-trastuzumab duocarmazine (SYD985) caused side effects like fatigue, low white blood cell count (neutropenia), lung inflammation (pneumonitis), and eye-related issues. These studies suggest it has some safety concerns, but more research is needed to fully understand its safety profile. ^{3 4 6 7 8}

How is the drug Vic-trastuzumab duocarmazine (SYD985) different from other treatments for HER2-expressing breast cancer?

Vic-trastuzumab duocarmazine (SYD985) is unique because it is an antibody-drug conjugate that targets HER2 and is more effective in low HER2-expressing breast cancers compared to other treatments like T-DM1. It works by efficiently releasing a potent toxin in tumor conditions, which allows it to kill cancer cells even in tumors with mixed HER2 expression levels. ^{3 9 10 11 12}

Research Team

Paula R Pohlmann, MD, MSc, PhD

Principal Investigator

M.D. Anderson Cancer Center

Anthony Elias, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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

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

Treatment Details

Interventions

• Vic-trastuzumab duocarmazine (SYD985)

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Adjuvant treatment of breast cancer: impact of monoclonal antibody therapy directed against the HER2 receptor. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Integrating trastuzumab in the neoadjuvant treatment of primary breast cancer: accumulating evidence of efficacy, synergy and safety. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

New ADC Shrinks HER2-Positive Tumors. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Ongoing and planned adjuvant trials with trastuzumab. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine in human epidermal growth factor receptor 2-positive breast cancer: a review. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics and immunogenicity of an antibody-drug conjugate (SHR-A1201) in patients with HER2-positive advanced breast cancer: an open, phase I dose-escalation study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

The potential for trastuzumab emtansine in human epidermal growth factor receptor 2 positive metastatic breast cancer: latest evidence and ongoing studies. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The Preclinical Profile of the Duocarmycin-Based HER2-Targeting ADC SYD985 Predicts for Clinical Benefit in Low HER2-Expressing Breast Cancers. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Trastuzumab-DM1 causes tumour growth inhibition by mitotic catastrophe in trastuzumab-resistant breast cancer cells in vivo. [2021]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

T-DM1 in the Neo-Adjuvant Treatment of HER2-Positive Breast Cancer: Impact of the KRISTINE (TRIO-021) Trial. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Trastuzumab-DM1: a clinical update of the novel antibody-drug conjugate for HER2-overexpressing breast cancer. [2021]