Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer (DB-06)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Advanced or Metastatic Breast Cancer

Treatments: Drug: Trastuzumab deruxtecan; Drug: Capecitabine; Drug: Paclitaxel; Drug: Nab-Paclitaxel

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT04494425

2019-004493-26 (EudraCT Number)

D9670C00001

Details and patient eligibility

About

This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.

Full description

Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC >0 <1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer.

The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.

Enrollment: 866 patients

Sex: All

Ages: 18 to 105 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Patients must be ≥18 years of age

• Pathologically documented breast cancer that:

  1. is advanced or metastatic
  2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
  3. has HER2-low or HER2 IHC >0 <1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
  4. was never previously HER2-positive
  5. is documented HR+ disease in the metastatic setting.

• No prior chemotherapy for advanced or metastatic breast cancer.

• Has adequate tumor samples for assessment of HER2 status

• Must have either:

  1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
  2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.

• Has protocol-defined adequate organ and bone marrow function

Key Exclusion Criteria:

• Ineligible for all options in the investigator's choice chemotherapy arm
• Lung-specific intercurrent clinically significant illnesses
• Uncontrolled or significant cardiovascular disease or infection
• Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening.
• Patients with spinal cord compression or clinically active central nervous system metastases
• Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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866 participants in 2 patient groups

Trastuzumab deruxtecan

Experimental group

Description:

Trastuzumab deruxtecan (T-DXd; DS-8201a) arm

Treatment:

Drug: Trastuzumab deruxtecan

Standard of Care

Active Comparator group

Description:

Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm

Treatment:

Drug: Nab-Paclitaxel

Drug: Paclitaxel

Drug: Capecitabine