Active, not recruiting • Phasen I, II • Stufe III, IV • Post-Menopausal • Brain Metastases present • Interventionell

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

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

Beschreibung

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.

Studiendesign

Zulassungskriterien

Arms and Intervention

• Trastuzumab deruxtecan

• Durvalumab

• Paclitaxel

• Pertuzumab

• Tucatinib

Einschlusskriterien

• patients must be at least 18 years of age

• pathologically documented breast cancer that:

• is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic

• her2-positive (ihc 3+ or ihc 2+/ish+) based on local assessment. the local her2 result must be from a tumour sample obtained in the metastatic setting.

• is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting

• patient must have adequate tumor sample from the metastatic setting for biomarker assessment

• ecog performance status of 0 or 1

• part 1

• disease progression on or after the last systemic therapy prior to starting study treatment

• 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

Ausschlusskriterien

• 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 at a total daily dose of > 2 mg dexamethasone or any brain lesion thought to require immediate local therapy