TRUDI: A Phase II Study of Neoadjuvant Trastuzumab Deruxtecan and Durvalumab for Stage III, HER2-expressing Inflammatory Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Trastuzumab deruxtecan
- Conditions
- Invasive Breast Cancer
- Sponsor
- Filipa Lynce, MD
- Enrollment
- 63
- Locations
- 3
- Primary Endpoint
- Pathological complete response (pCR) Rate
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
The purpose of this study is to test the safety and effectiveness of an investigational drug combination (trastuzumab deruxtecan and durvalumab) to learn whether the intervention works in treating Human Epidermal growth factor Receptor-2 (HER2)-expressing inflammatory breast cancer.
The names of the study drugs involved in this study are:
- Trastuzumab deruxtecan
- Durvalumab
Detailed Description
This is a phase 2 open label study of neoadjuvant trastuzumab deruxtecan plus durvalumab for patients with stage III, HER2-positive or HER2-low inflammatory breast cancer (IBC), who have not received prior therapy for ipsilateral breast cancer. Participants will be enrolled into one of two study treatment groups: HER2 positive IBC (Cohort 1) or HER2 low IBC (Cohort 2). Research procedures including screening for eligibility, clinic visits for treatment, tumor biopsies, and blood tests. The U.S. Food and Drug Administration (FDA) has not approved Durvalamab or Trastuzumab deruxtecan for inflammatory breast cancer, but both have been approved for other uses. Participation in this study is expected to last about 22 months. It is expected that about 63 people will take part in this research study. The pharmaceutical company, AstraZeneca, is supporting this research study by providing the study drugs and funding.
Investigators
Filipa Lynce, MD
Sponsor Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •Participants must have a histological or cytological diagnosis of invasive breast cancer.
- •All histologic subtypes are eligible.
- •Participants must have a clinical diagnosis of stage III inflammatory breast cancer within the past 6 months
- •HER2-positive status as determined locally by the current ASCO/CAP guidelines or HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) (note: ISH may be determined by either fluorescence in situ hybridization \[FISH\] or dual in situ hybridization \[DISH\])
- •Any ER and PR expressions are permitted but must be known
- •Participants must be treatment-naïve
- •Participants must agree to undergo two research biopsies of the tumor (if safely accessible, as determined by the treating investigator): at baseline (prior to the first treatment) and after the first week of treatment on C1D
- •Previously collected archival tissue will also be obtained on all participants. For participants for whom the tumor is not safely accessible, this archival tissue needs to be located and availability confirmed at time of registration.
- •Pre- and postmenopausal women or male patients ≥ 18 years of age
- •ECOG performance status 0-1 (Karnofsky \> 60%, see Appendix A).
Exclusion Criteria
- •Has received prior systemic anti-cancer therapy for the current diagnosis of inflammatory breast cancer, including chemotherapy, immunotherapy, or targeted therapy
- •Has received any radiotherapy or surgery for the current diagnosis of inflammatory breast cancer. Tumor biopsies are not considered surgery for the purpose of enrollment.
- •Prior hypersensitivity to durvalumab or the excipients of durvalumab or trastuzumab deruxtecan or history of severe hypersensitivity reactions to other monoclonal antibodies.
- •Major surgery within 4 weeks prior to study treatment initiation. Patients must have recovered from any effects of any major surgery.
- •Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
- •Participant has a medical condition that requires chronic systemic steroid therapy (\> 10 mg of prednisone daily or equivalent) or any other form of immunosuppressive medication (including disease modifying agents) and has required such therapy in the last 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic therapy.
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, and rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion:
- •\-- Patients with vitiligo or alopecia, Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, Patients with any chronic skin condition that does not require systemic therapy, Patients with celiac disease controlled by diet alone, who may also be included, but only after consultation with the Principal Investigator, Patients without active disease in the last 5 years, who may also be included but only after consultation with the Principal Investigator
- •History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), and prior pneumonectomy
Arms & Interventions
HER2 Positive
Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2). * HER2-positive determined locally by the current ASCO/CAP guidelines * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery. (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care.
Intervention: Trastuzumab deruxtecan
HER2 Positive
Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2). * HER2-positive determined locally by the current ASCO/CAP guidelines * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery. (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care.
Intervention: Durvalumab
HER2-Low
Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2) * HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care.
Intervention: Trastuzumab deruxtecan
HER2-Low
Participants will be enrolled into one of two cohorts: HER2 positive IBC (cohort 1) and HER2 low IBC (cohort 2) * HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) * Participants will receive trastuzumab deruxtecan plus durvalumab for eight cycles prior to surgery (Cycle Length is 21 days) * After surgery, Participants will receive therapy per physician's choice and to reflect current standard of care.
Intervention: Durvalumab
Outcomes
Primary Outcomes
Pathological complete response (pCR) Rate
Time Frame: Assessed on surgical tissue: surgery occurs no later than 6 weeks post 8 cycles of neo-adjuvant therapy (one cycle=21 days)
pCR rate is the proportion of participants with absent invasive carcinoma in the breast and lymph nodes at time of surgery; in situ disease only is considered pCR; if off-treatment prior to surgery than considered not pCR.
Secondary Outcomes
- Distant progression or distant disease-free survival (DP/DDFS)(Disease assessed every 6 weeks by chest xray (+/- 1 week) until 8 cycles of neo-adjuvant therapy (one cycle=21 days); Follow-up assessments post-surgery every 6 months (+/- 8 weeks) until participant withdrawal or death up to 4 years)
- Event Free Survival (EFS)(Disease assessed every 6 weeks by chest xray (+/- 1 week) until completion of 8 cycles of neo-adjuvant therapy (one cycle=21 days); Follow-up assessments post-surgery every 6 months (+/- 8 weeks) until participant withdrawal or death up to 4 years)
- Residual Cancer Burden (RCB) Response(Assessed on surgical tissue; surgery occurs +day 14 and no later than 6 weeks post 8 cycles of neo-adjuvant therapy (one cycle=21 days))