臨床研究等提出・公開システム

A Phase 3, Randomized, Open-label, Multicenter, Controlled Study to Evaluate the Efficacy and Safety of Zanidatamab in Combination With Physician's Choice Chemotherapy Compared to Trastuzumab in Combination With Physician's Choice Chemotherapy for the Treatment of Participants With Metastatic HER2-positive Breast Cancer Who Have Progressed on, or Are Intolerant to, Previous Trastuzumab Deruxtecan Treatment

A Study Comparing the Efficacy and Safety of Zanidatamab to Trastuzumab, Each in Combination With Physician's Choice Chemotherapy, for the Treatment of Participants With Metastatic HER2 positive Breast Cancer

Sakagami Yohei

PPD-SNBL K. K.

St Luke's Tover 12F, 8-1 Akashi-cho, Chuo-ku, Tokyo

CRGPPDSNBL-9-Jazz_JZP598-303_Japan_CRA@Thermofisher.com

Sakagami Yohei

PPD-SNBL K. K.

St Luke's Tover 12F, 8-1 Akashi-cho, Chuo-ku, Tokyo

+81-90-1409-9855

CRGPPDSNBL-9-Jazz_JZP598-303_Japan_CRA@Thermofisher.com

Recruiting

Dec. 02, 2024

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Is 18 years of age or of the legal adult age per local standard at the time of signing the informed consent.

2. Has histologically confirmed HER2-positive breast cancer according to ASCO-CAP Guidelines as evaluated by a central laboratory.

3. Participants with unresectable or metastatic HER2 positive breast cancer who have progressed on, or are intolerant to, previous T-DXd treatment.

4. Has measurable disease per RECIST version 1.1.

5. Is eligible to receive one of the chemotherapy options listed in the physician choice of chemotherapy (eribulin, gemcitabine, vinorelbine, or capecitabine).

6. Participants with history of treated or clinically inactive CNS metastases are eligible as specified in the protocol.

7. Has a life expectancy of at least 6 months, in the opinion of the investigator.

8. Has adequate hematologic parameters as defined in the protocol.

9. Has adequate hepatic function as specified in the protocol.

10. Has creatinine clearance >= 30 mL/minute as calculated per local institutional guidelines.

11. Has LVEF >= 50% as determined by either echocardiogram or MUGA obtained within 4 weeks before the first dose of study intervention.

12. Has ECOG performance status of 0 or 1.

13. Participant agrees to the following based on sex assigned at birth.
1. Male participants:
Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 5 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance or standard practice, whichever is longer:
Refrain from donating fresh unwashed semen.
Use contraception as follows as specified in the protocol
2. Female participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
Is a women of nonchildbearing potential OR
Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency during the study intervention period and for at least 5 months after the last dose of study intervention or the contraception period for the combination chemotherapy of choice per local guidance or standard practice, whichever is longer.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 3 days before the first dose of study intervention.
Additional requirements for pregnancy testing during and after study intervention are provided in the protocol.
The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

14. Is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the protocol.

1. Has known or suspected leptomeningeal disease.

2. Has uncontrolled or significant cardiovascular disease.

3. Has toxicity related to prior cancer therapy that has not resolved to =< Grade 1, with exceptions as stated in the protocol.

4. Has uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.

5. Has known HIV infection.

6. Has active hepatitis B or C infection.

7. Has an active SARS-CoV-2 infection. Participants with prior infection that has resolved per local institutions' requirements and screening guidance are eligible.

8. Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab.

9. Is unable to receive trastuzumab treatment due to medical contraindications.

10. Has any serious underlying medical or psychiatric condition that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site.

11. Has any condition that would prevent treatment with the physician's choice of chemotherapy.

12. Has any issue or condition that in the opinion of the investigator would contraindicate the participant's participation in the study or confound the results of the study.

13. Has a history of prior allogeneic bone marrow, stem cell, or solid organ transplantation.

14. Was treated with any local or systemic antineoplastic therapy (including hormonal therapies for breast cancer) or any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to randomization.

15. Has a history of trauma or major surgery within 4 weeks prior to randomization.

16. Has a known hypersensitivity to any components of the study drugs, including chemotherapy.

17. Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.

Both

HER2-positive metastatic breast cancer

For subjects weighing less than 70 kg, 1,800 mg is administered IV on Day 1 of each 21-day cycle. For subjects weighing 70 kg or more, 2,400 mg is administered IV on Day 1 of each 21-day cycle.

Progression-free Survival (PFS) Per RECIST Version 1.1 As Assessed by Blinded Independent Central Review (BICR)

+81-3-3784-8305

Oct. 22, 2024

No

Austria/Belgium/Brazil/Canada/France/Germany/Greece/Italy/Poland/South Korea/Spain/United Kingdom/USA