A Phase 1b Study of T-DXd Combinations in HER2-low Advanced or Metastatic Breast Cancer

NCT04556773 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: D967JC000022023-505690-33-002020-002797-27
• Study Type: interventional
• Target: 138
• Locations: 10 countries
• Sites: 37

Brief Summary

DESTINY-Breast 08 will investigate the safety, tolerability, PK and preliminary anti-tumour activity of T-DXd in combination with other therapies in patients with Metastatic HER2-low Advanced or Metastatic Breast Cancer

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer; HER2-negative; HER2-low; Trastuzumab Deruxtecan; T-DXd; DS-8201a; DESTINY-Breast08; Anti-HER2 Antibody Drug Conjugate (ADC); Triple-negative breast cancer (TNBC)

Outcome Measures

Primary Outcomes (4)

• Occurrence of adverse events (AEs)- Part 1

  Occurrence of AEs in Part 1 graded according to NCI CTCAE v5.0

  Up to follow-up period, approximately 24 months

• Occurrence of serious adverse events (SAEs)- Part 1

  Occurrence of SAEs in Part 1 graded according to NCI CTCAE v5.0

  Up to follow-up period, approximately 24 months

• Occurrence of adverse events (AEs)- Part 2

  Occurrence of AEs in Part 2 graded according to NCI CTCAE v5.0

  Up to follow-up period, approximately 24 months

• Occurrence of serious adverse events (SAEs)- Part 2

  Occurrence of SAEs in Part 2 graded according to NCI CTCAE v5.0

  Up to follow-up period, approximately 24 months

Secondary Outcomes (8)

• Objective Response Rate (ORR)- Part 2

  Until progression, assessed up to approximately 24 months

• Progression Free Survival (PFS)- Part 2

  Until progression or death, assessed up to approximately 24 months

• Duration of Response (DoR)- Part 2

  Until progression or death, assessed up to approximately 24 months

• Overall Survival (OS)- Part 2

  Until death, assessed up to approximately 24 months

• Serum concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a

  While on study drug up to study completion, approximately 24 months

Study Arms (5)

Module 1: T-DXd + capecitabine

EXPERIMENTAL

T-DXd: 5.4 mg/kg Q3W, intravenous use Capecitabine: 1000mg/m2 BID, days 1-14 Q3W, oral use

Drug: Trastuzumab deruxtecan; Drug: Capecitabine

Module 2: T-DXd + durvalumab + paclitaxel

EXPERIMENTAL

T-DXd: 5.4 mg/kg Q3W, intravenous use Durvalumab: 1120 mg Q3W, intravenous use Paclitaxel: 80 mg/m2 QW in 3-week cycles, intravenous use

Drug: Trastuzumab deruxtecan; Drug: Durvalumab; Drug: Paclitaxel

Module 3: T-DXd + capivasertib

EXPERIMENTAL

T-DXd: 5.4 mg/kg Q3W, intravenous use Capivasertib: 400 mg BID, oral use

Drug: Trastuzumab deruxtecan; Drug: Capivasertib

Module 4: T-DXd + anastrozole

EXPERIMENTAL

T-DXd: 5.4 mg/kg Q3W, intravenous use Anastrozole: 1 mg daily, oral

Drug: Trastuzumab deruxtecan; Drug: Anastrozole

Module 5: T-DXd + fulvestrant

EXPERIMENTAL

T-DXd: 5.4 mg/kg Q3W, intravenous use Fulvestrant: 500 mg Q4W, intramuscular use

Drug: Trastuzumab deruxtecan; Drug: Fulvestrant

Interventions

Durvalumab DRUG

Durvalumab: administered as an IV infusion

Also known as: MEDI4736

Module 2: T-DXd + durvalumab + paclitaxel

Paclitaxel DRUG

Paclitaxel: administered as an IV infusion

Also known as: Taxol A

Module 2: T-DXd + durvalumab + paclitaxel

Capivasertib DRUG

Capivasertib: administered orally

Also known as: AZD5363

Module 3: T-DXd + capivasertib

Anastrozole DRUG

Anastrozole: administered orally

Also known as: Anastrozol

Module 4: T-DXd + anastrozole

Fulvestrant DRUG

Fulvestrant: administered as an IM injection

Module 5: T-DXd + fulvestrant

Capecitabine DRUG

Capecitabine: administered orally

Module 1: T-DXd + capecitabine

Trastuzumab deruxtecan DRUG

T-DXd: administered as an IV infusion

Also known as: DS-8201a, T-DXd

Module 1: T-DXd + capecitabine; Module 2: T-DXd + durvalumab + paclitaxel; Module 3: T-DXd + capivasertib; Module 4: T-DXd + anastrozole; Module 5: T-DXd + fulvestrant

Eligibility Criteria

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

You may qualify if:

• Patients must be at least 18 years of age
• Male or female patients who have pathologically documented breast cancer that:
• Has a history of HER2-low expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) with a validated assay
• Is documented as HR+ (either ER and/or PgR positive \[ER or PgR ≥1%\]) or ER and PgR negative (ER and PgR \<1%) per ASCO/CAP guidelines in the metastatic setting
• Patient must have adequate tumor sample for biomarker assessment
• ECOG Performance Status of 0 or 1
• For patients with HR+ disease:
• Part 1: At least 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors), and at least 1 prior line of chemotherapy for MBC are required.
• Part 2: Only 1 prior treatment line of ET with or without a targeted therapy (such as CDK4/6, mTOR or PI3-K inhibitors) for MBC is allowed. No prior chemotherapy in the metastatic setting is allowed. Note there are no patients with HR+ disease in Part 2 of Modules 2 and 3.
• For patients with HR- disease:
• Part 1: At least 1 prior line of chemotherapy for MBC is required. Note there are no patients with HR- disease in Part 1 of Modules 4 and 5.
• Part 2: For Module 2, no prior lines of therapy for MBC are allowed, and for Modules 1 and 3, only 1 prior line of chemotherapy for MBC is allowed. Note there are no patients with HR- disease in Part 2 of Modules 4 and 5.

You may not qualify if:

• Uncontrolled intercurrent illness
• Uncontrolled or siginificant cardiovascular disease
• 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
• Has spinal cord compression or clinically active central nervous system metastases
• Active primary immunodeficiency
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Prior treatment with ADC that comprises of an exatecan derivative that is a topoisomerase I inhibitor.

Sponsors & Collaborators

• AstraZeneca: lead
• Daiichi Sankyo Co., Ltd.: collaborator
• Daiichi Sankyo Company, Limited: collaborator

Study Sites (37)

Research Site

Commack, New York, 11725, United States

Location

Research Site

Harrison, New York, 10604, United States

Location

Research Site

New York, New York, 10029, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Uniondale, New York, 11553, United States

Location

Research Site

Chapel Hill, North Carolina, 27514, United States

Location

Research Site

Chattanooga, Tennessee, 37404, United States

Location

Research Site

Germantown, Tennessee, 38138, United States

Location

Research Site

Fort Worth, Texas, 76104, United States

Location

Research Site

East Melbourne, 3002, Australia

Location

Research Site

Westmead, 2145, Australia

Location

Research Site

Edegem, 2650, Belgium

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Ottignies, 1340, Belgium

Location

Research Site

Goiânia, 74605-070, Brazil

Location

Research Site

Porto Alegre, 90035-003, Brazil

Location

Research Site

Porto Alegre, 90110-270, Brazil

Location

Research Site

São Paulo, 03102-002, Brazil

Location

Research Site

São Paulo, 04543-000, Brazil

Location

Research Site

Kelowna, British Columbia, V1Y 5L3, Canada

Location

Research Site

Québec, Quebec, G1J 1Z4, Canada

Location

Research Site

Villejuif, 94805, France

Location

Research Site

Monterrey, 64710, Mexico

Location

Research Site

Moscow, 115478, Russia

Location

Research Site

Moscow, 143442, Russia

Location

Research Site

Saint Petersburg, 199226, Russia

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Kaohsiung City, 82445, Taiwan

Location

Research Site

Taichung, 40443, Taiwan

Location

Research Site

Taipei, 100, Taiwan

Location

Research Site

Taipei, 11217, Taiwan

Location

Research Site

Taipei, 114, Taiwan

Location

Research Site

Taipei, 235, Taiwan

Location

Research Site

Taoyuan District, 333, Taiwan

Location

Related Links

• AstraZeneca Breast Cancer Study Locator website - To learn which AstraZeneca breast cancer clinical trials are looking for participants with specific diagnosis, stage, and treatment history.
• redacted Study Synopsis (core + module 1-5 (combined)

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

trastuzumab deruxtecan; durvalumab; Paclitaxel; capivasertib; Anastrozole; Fulvestrant; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Komal Jhaveri, MD, FACP

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will initially consist of 5 treatment modules, each of which includes T-DXd in combination with other anti-cancer agents. Each module will have 2 parts: a dose-finding phase (Part 1) and a dose-expansion phase (Part 2). The Part 2 dose-expansion phase will use the recommended Phase 2 dose (RP2D) for the combination, either as determined in Part 1 or from another clinical study if appropriate. For each module, patients will be centrally assigned to one of the open modules, as per the module specific criteria. In addition to safety and tolerability, this study will also assess ORR, PFS, DoR, and OS for each treatment combination.

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: September 21, 2020
• Study Start: December 17, 2020
• Primary Completion: August 16, 2023
• Study Completion (Estimated): June 16, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

KR (4); RU (3); AU (2); FR (1); ME (1); BE (3); US (9); BR (5); TW (7); CA (2)