Genomic and Transcriptomic Predictors of Sequential SG Sensitivity After T-DXd in ER+/HER2-Low Metastatic Breast Cancer

NCT06665178 | Recruiting Phase 2

• 1 other identifier: SG6822
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Advanced hormone positive (HR+), HER2 negative breast cancer continues to pose a challenge when patients have progressed on CDK4/6 inhibitor and endocrine therapy leaving limited treatment options. Antibody-drug conjugates (ADCs) such as sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have changed practice due to significant improvement in progression free survival (PFS) and overall survival (OS) seen in this disease setting. There is a genuine interest to use SG sequentially after T-DXd, however there is no current prospectively curated evidence to support this strategy. Though the epitope is different, the payload are both topoisomerase I inhibitors. Thus, evidence is needed of both clinical efficacy and identification of mechanisms of sensitivity and resistance to sequential ADCs in HER-2 low MBC. It is hypothesized that performing whole genome and whole transcriptome sequencing in fresh tumour biopsies post progression of T-DXd and prior to SG in ER+/HER2 low metastatic breast cancer (MBC) will provide mechanistic insights into identifying biomarkers, and thus patients, sensitive to sequential SG.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Altered Tumor Genes by PFS Duration on SG Post T-DXd

  Number and identification of altered/mutated genes in the tumors in the subgroup of patients with a longer PFS on SG post T-DXd compared to the tumors in the subgroup of patients with a shorter PFS on SG post T-DXd.

  Up to an average of 6 months

Secondary Outcomes (6)

• Progression free survival (PFS)

  Up to an average of 6 months

• Response rate (RR)

  Up to an average of 6 months

• Grade 2-4 toxicities

  Up to an average of 3 months

• Overall survival

  Up to an average of 12 months

• Trop-2 expression and HER-2 expression

  Up to an average of 12 months

Study Arms (1)

Sacituzumab Govitecan

EXPERIMENTAL

Patients will receive SG at an initial dose of 10 mg per kilogram intravenously on day 1 and 8 of 21 day cycles.

Drug: Sacituzumab Govitecan

Interventions

Sacituzumab Govitecan DRUG

Administer Sacituzumab Govitecan (SG) at 10 mg/kg as an intravenous (IV) infusion on Days 1 and 8 of a 21-day cycle. SG should not be administered as an IV push or bolus.

Sacituzumab Govitecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide signed informed consent approved by UBC/BC Cancer REB
• Female or male patients, regardless of race and ethnic group, who are ≥18 years old at the time of informed consent
• Patients with locally advanced or metastatic ER+/HER2 low (defined as IHC 1+ or 2+ but FISH or CISH negative by ratio as per ASCO/CAP guidelines) breast cancer. Patients with imaging confirmed inoperable locally advanced breast cancer for which treatment is palliative in intent are also permitted.
• Prior treatment must have included prior endocrine based treatment in the metastatic setting in conjunction with a CDK4/6 inhibitor.
• Prior treatment must include at least 1 line of chemotherapy which must include trastuzumab deruxtecan (T-DXd) as the immediate prior line of therapy prior to study enrollment
• The tumour must be accessible to be able to safely perform image guided biopsies for WGS and WTS.
• Negative serum pregnancy test at baseline for pre-menopausal patients (within 14 days prior to randomization) and agreement to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of SG
• Patients can have measurable or non measurable (but assessable) disease by CT or MRI as per RECIST Version 1.1 criteria as evaluated locally. Tumor lesions situated in a previously irradiated area are considered measurable if unequivocal progression has been documented in such lesions since radiation.
• ECOG PS 0-2
• Life expectancy ≥ 3 months
• Acceptable bone marrow and organ function defined by the following laboratory values:
• Absolute neutrophil count ≥1.0 x 109/L
• Platelets ≥100 x 109/L
• Hemoglobin ≥9.0 g/dL
• INR ≤1.5

You may not qualify if:

• Patient is currently participating in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Patient has a known hypersensitivity to SG, irinotecan or its active metabolite SN-38.
• Patients not available for follow up
• Patients who are not willing to consider systemic treatment options
• Tumor not accessible or not safe to perform biopsies
• Patient has not had resolution of all acute toxic effects of prior anti-cancer therapy to CTCAE v. 5.0 grade ≤1 (except toxicities not considered a safety risk for the patient at investigators discretion: e.g. grade 2 peripheral neuropathy from prior chemotherapy that is stable).
• Have an active second malignancy. Patients with a history of malignancy that has been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (e.g. non-melanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll.
• Have known active central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they have stable CNS disease (defined as no longer symptomatic from brain metastasis or no longer requires higher doses of corticosteroids (\> 10 mg Dexamethasone per day) for CNS symptom management. Anticonvulsants and stable corticosteroids dose can be included in the study). Screening for brain metastasis not required for enrollment.
• Pregnancy and breast feeding
• Patient has a pre-existing condition with uncontrolled diarrhea, chronic inflammatory bowel disease or GI perforation within 6 months prior to enrollment.
• Have active serious infection requiring antibiotics.

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• Gilead Sciences: collaborator

Study Sites (1)

BC Cancer - Vancouver Center

Vancouver, British Columbia, V5Z4E6, Canada

RECRUITING

Related Publications (3)

• Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. doi: 10.1056/NEJMoa2203690. Epub 2022 Jun 5.

  PMID: 35665782 BACKGROUND

• Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortes J, O'Shaughnessy J, Dieras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi: 10.1056/NEJMoa2028485.

  PMID: 33882206 BACKGROUND

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

Related Links

• Jones, S.J., Laskin, J., Li, Y.Y. et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biol 11, R82 (2010).
• Pleasance E, Titmuss E, Williamson L et al. Pan-cancer analysis of advanced patient tumors reveals interactions between therapy and genomic landscapes.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

sacituzumab govitecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Stephen Chia, MD

CONTACT

604-877-6000; schia@bccancer.bc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist, BC Cancer

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 30, 2024
• Study Start: March 31, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)