A Phase 1b/2 Study of T-DXd Combinations in HER2-positive Metastatic Breast Cancer

A Phase 1b/2 Multicentre, Open-label, Modular, Dose-finding and Dose-expansion Study to Explore the Safety, Tolerability, and Anti-tumour Activity of Trastuzumab Deruxtecan (T-DXd) in Combination With Other Anti-cancer Agents in Patients With HER2-positive Metastatic Breast Cancer (DESTINY-Breast07)

Sponsors

Lead Sponsor: AstraZeneca

Collaborator: Daiichi Sankyo Company, Limited

Source AstraZeneca
Brief Summary

DESTINY-Breast07 will investigate the safety, tolerability, and anti-tumour activity of trastuzumab deruxtecan (T-DXd) in combination with other anti-cancer agents in patients with HER2-positive Metastatic Breast Cancer

Detailed Description

This study is modular in design allowing assessment of safety, tolerability and anti-tumour activity of T-DXd in combination with other anti-cancer agents. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the recommended Phase 2 dose (RP2D) determined in Part 1 will be used for the dose-expansion in Part 2. The target population of interest in this study is patients with HER2-positive (as per ASCO/CAP 2018 guidelines) advanced/MBC inclusive of patients with active and stable brain metastases. Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.

Overall Status Recruiting
Start Date 2020-12-28
Completion Date 2025-04-30
Primary Completion Date 2025-04-30
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Occurrence of adverse events (AEs)- Part 1 Up to follow-up period, approximately 53 months
Occurrence of serious adverse events (SAEs)- Part 1 Up to follow-up period, approximately 53 months
Occurrence of adverse events (AEs)- Part 2 Up to follow-up period, approximately 53 months
Occurrence of serious adverse events (SAEs)- Part 2 Up to follow-up period, approximately 53 months
Secondary Outcome
Measure Time Frame
Objective Response Rate (ORR)- Part 2 Until progression, assessed up to approximately 53 months
Progression Free Survival (PFS)- Part 2 Until progression, assessed up to approximately 53 months
Progression Free Survival 2 (PFS2)- Part 2 Assessed up to approximately 53 months
Duration of Response (DoR)- Part 2 Until progression, assessed up to approximately 53 months
Overall Survival (OS)- Part 2 Until death, assessed up to approximately 53 months
Serum Concentration of Trastuzumab Deruxtecan (T-DXd) While on study drug up to study completion, approximately 53 months
Serum Concentration of Durvalumab While on study drug up to study completion, approximately 53 months
Serum Concentration of Pertuzumab While on study drug up to study completion, approximately 53 months
Plasma Concentration of Paclitaxel While on study drug up to study completion, approximately 53 months
Plasma Concentration of Tucatinib While on study drug up to study completion, approximately 53 months
Immunogenicity of trastuzumab deruxtecan Up to follow-up period, approximately 53 months
Immunogenicity of Durvalumab Up to follow-up period, approximately 53 months
Immunogenicity of Pertuzumab Up to follow-up period, approximately 53 months
Enrollment 450
Condition
Intervention

Intervention Type: Drug

Intervention Name: Trastuzumab deruxtecan

Description: T-DXd: administered as an IV infusion

Other Name: DS-8201a, T-DXd

Intervention Type: Drug

Intervention Name: Durvalumab

Description: Durvalumab: administered as an IV infusion

Other Name: MEDI4736

Intervention Type: Drug

Intervention Name: Paclitaxel

Description: Paclitaxel: administered as an IV infusion

Intervention Type: Drug

Intervention Name: Pertuzumab

Description: Pertuzumab: administered as an IV infusion

Arm Group Label: Module 2- T-DXd and Pertuzumab

Intervention Type: Drug

Intervention Name: Tucatinib

Description: Tucatinib administered orally (tablet) twice daily

Other Name: ONT-380

Eligibility

Criteria:

Key Inclusion Criteria: - Patients must be at least 18 years of age - Pathologically documented breast cancer that: 1. Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic 2. HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment 3. Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting - Patient must have adequate tumor sample for biomarker assessment - ECOG Performance Status of 0 or 1 - Part 1 1. Disease progression on or after the last systemic therapy prior to starting study treatment 2. At least 1 prior treatment line in metastatic setting required. - Part 2 (Modules 0 - 5) a) No prior lines of therapy for advanced/MBC allowed - Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed CNS Inclusion - Modules 0 - 5 Patients must have no brain metastases or stable brain metastases. - Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy Key Exclusion Criteria: - Uncontrolled or significant cardiovascular disease - Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening - Lung-specific intercurrent clinically significant illnesses - Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals - Spinal cord compression or a history of leptomeningeal carcinomatosis - Prior treatment with immune checkpoint inhibitors - Prior treatment with an ADC containing a topoisomerase I inhibitor - Prior treatment with tucatinib CNS Exclusion - Modules 0 - 5: Has untreated brain metastasis - Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of brain metastases or brain lesion thought to require immediate local therapy

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Contact

Last Name: AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Location
Facility: Status:
Research Site | Los Angeles, California, 90048, United States Suspended
Research Site | Leesburg, Florida, 34748, United States Not yet recruiting
Research Site | Saint Petersburg, Florida, 33705, United States Not yet recruiting
Research Site | Saint Paul, Minnesota, 55101, United States Recruiting
Research Site | Montvale, New Jersey, 07645, United States Not yet recruiting
Research Site | Commack, New York, 11725, United States Not yet recruiting
Research Site | New York, New York, 10016, United States Recruiting
Research Site | Nashville, Tennessee, 37203, United States Recruiting
Research Site | Fort Worth, Texas, 76104, United States Recruiting
Research Site | Fairfax, Virginia, 22031, United States Recruiting
Research Site | Melbourne, 3000, Australia Recruiting
Research Site | Barretos, 14784-400, Brazil Not yet recruiting
Research Site | Belo Horizonte, 30150-270, Brazil Not yet recruiting
Research Site | Natal, 59075-740, Brazil Not yet recruiting
Research Site | Porto Alegre, 90610-000, Brazil Not yet recruiting
Research Site | Porto Alegre, 91350-200, Brazil Not yet recruiting
Research Site | Rio de Janeiro, 20560-120, Brazil Not yet recruiting
Research Site | Sao Paulo, 01317-001, Brazil Not yet recruiting
Research Site | Sao Paulo, 04029-000, Brazil Not yet recruiting
Research Site | Sorocaba, 18030-510, Brazil Not yet recruiting
Research Site | Edmonton, Alberta, T6G 1Z2, Canada Not yet recruiting
Research Site | Montreal, Quebec, H2X 0A9, Canada Recruiting
Research Site | Montreal, Quebec, H3T 1E2, Canada Not yet recruiting
Research Site | Quebec, G1S 4L8, Canada Recruiting
Research Site | Toronto, M5G 2M9, Canada Not yet recruiting
Research Site | Villejuif Cedex, 94805, France Recruiting
Research Site | Berlin, 12200, Germany Suspended
Research Site | Bottrop, 46236, Germany Not yet recruiting
Research Site | Düsseldorf, 40225, Germany Not yet recruiting
Research Site | Erlangen, 91054, Germany Not yet recruiting
Research Site | Halle, 6120, Germany Not yet recruiting
Research Site | München, 80637, Germany Not yet recruiting
Research Site | München, 81675, Germany Not yet recruiting
Research Site | Würzburg, 97080, Germany Not yet recruiting
Research Site | Gurgaon, 122001, India Recruiting
Research Site | Madurai, 625107, India Recruiting
Research Site | Mumbai, 400012, India Recruiting
Research Site | Mumbai, 400053, India Suspended
Research Site | Rohini, 110 085, India Recruiting
Research Site | Bologna, 40138, Italy Recruiting
Research Site | Milan, 20141, Italy Recruiting
Research Site | Napoli, 80131, Italy Recruiting
Research Site | Rome, 00168, Italy Not yet recruiting
Research Site | Seoul, 03080, Korea, Republic of Recruiting
Research Site | Seoul, 05505, Korea, Republic of Recruiting
Research Site | Seoul, 06351, Korea, Republic of Not yet recruiting
Research Site | Bydgoszcz, 85-796, Poland Not yet recruiting
Research Site | Koszalin, 75-581, Poland Not yet recruiting
Research Site | Lublin, 20-090, Poland Not yet recruiting
Research Site | Warszawa, 02-034, Poland Not yet recruiting
Research Site | Łódź, 90-242, Poland Not yet recruiting
Research Site | Moscow, 105229, Russian Federation Recruiting
Research Site | Moscow, 109240, Russian Federation Not yet recruiting
Research Site | Moscow, 111123, Russian Federation Recruiting
Research Site | Moscow, 115478, Russian Federation Recruiting
Research Site | Moscow, 117997, Russian Federation Recruiting
Research Site | Moscow, 121205, Russian Federation Recruiting
Research Site | Moscow, 143423, Russian Federation Recruiting
Research Site | Saint Petersburg, 195271, Russian Federation Recruiting
Research Site | Sankt-Peterburg, 197758, Russian Federation Recruiting
Research Site | L'Hospitalet de Llobregat, 08908, Spain Recruiting
Research Site | Madrid, 28007, Spain Recruiting
Research Site | Madrid, 28050, Spain Recruiting
Research Site | Hualien, 970, Taiwan Recruiting
Research Site | Tainan, 704, Taiwan Recruiting
Research Site | Taipei City, 114, Taiwan Recruiting
Research Site | Taipei, 10048, Taiwan Recruiting
Research Site | Taipei, 10449, Taiwan Recruiting
Research Site | Taipei, 11217, Taiwan Recruiting
Research Site | Taipei, 235, Taiwan Recruiting
Research Site | Taoyuan City, 333, Taiwan Recruiting
Research Site | Ankara, 6100, Turkey Recruiting
Research Site | Edirne, 22030, Turkey Recruiting
Research Site | Istanbul, 34662, Turkey Recruiting
Research Site | Istanbul, 34722, Turkey Recruiting
Research Site | Izmir, 35100, Turkey Recruiting
Research Site | Buckhurst Hill, IG9 5HX, United Kingdom Not yet recruiting
Research Site | Cambridge, CB2 2QQ, United Kingdom Not yet recruiting
Research Site | Glasgow, G12 0YN, United Kingdom Not yet recruiting
Research Site | London, EC1A 7BE, United Kingdom Not yet recruiting
Research Site | London, SE19RT, United Kingdom Not yet recruiting
Research Site | Oxford, OX3 7LE, United Kingdom Not yet recruiting
Location Countries

Australia

Brazil

Canada

France

Germany

India

Italy

Korea, Republic of

Poland

Russian Federation

Spain

Taiwan

Turkey

United Kingdom

United States

Verification Date

2021-09-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 8
Arm Group

Label: Module 1- T-DXd and Durvalumab

Type: Experimental

Description: T-DXd and Durvalumab

Label: Module 2- T-DXd and Pertuzumab

Type: Experimental

Description: T-DXd and Pertuzumab

Label: Module 3- T-DXd and Paclitaxel

Type: Experimental

Description: T-DXd and Paclitaxel

Label: Module 4- T-DXd and Durvalumab and Paclitaxel

Type: Experimental

Description: T-DXd and Durvalumab and Paclitaxel

Label: Module 0- T-DXd

Type: Experimental

Description: T-DXd

Label: Module 5 - T-DXd and Tucatanib

Type: Experimental

Description: T-DXd and tucatinib

Label: Module 6 - T-DXd and Tucatinib

Type: Experimental

Description: T-DXd and tucatinib in patients with active brain metastases (Part 2 Only)

Label: Module 7 - T-DXd

Type: Experimental

Description: T-DXd monotherapy in patients with active brain metastases (Part 2 Only)

Acronym DB-07
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Sequential Assignment

Intervention Model Description: The study will consist of 2 phases: a dose escalation phase (Part 1) and a dose expansion phase (Part 2). Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later.Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease.

Primary Purpose: Treatment

Masking: None (Open Label)

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