Phase II Trial Evaluating the Safety and Efficacy of the Combination of Zimberelimab, Domvanalimab and Sacituzumab Govitecan as 1L Therapy for PD-L1 Positive Advanced TNBC

NCT07134556 | Withdrawn Phase 2

• 2 other identifiers: MEDOPP06532025-521489-80
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The ADJUNCT is a single-arm, phase II clinical trial to evaluate the safety and efficacy of the combination of zimberelimab, domvanalimab and sacituzumab govitecan as first-line therapy for patients with PD-L1 positive advanced or metastatic triple-negative breast cancer.

Conditions

PDL-1 Positive; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy in terms of objective response rate (ORR) as per RECIST v.1.1.

  ORR rate defined as the rate of patients with complete response (CR) or partial response (PR) as determined locally by the investigator in accordance RECIST v.1.1.

  Approximately 1 year

Secondary Outcomes (9)

• Efficacy in terms of PFS as per RECIST v.1.1.

  Aproximately 1 year

• Efficacy in terms of Overall Survival.

  Aproximately 1 year

• Efficacy in terms of Clinical benefit rate (CBR) as per RECIST v.1.1.

  Aproximately 1 year

• Efficacy in terms of Time to response (TTR) as per RECIST v.1.1.

  Aproximately 1 year

• Efficacy in terms of Duration of response (DoR) as per RECIST v.1.1.

  Aproximately 1 year

Study Arms (1)

zimberelimab, domvanalimab and sacituzumab govitecan

EXPERIMENTAL

patients will receive zimberelimab as an intravenous infusion (IV) at a dose of 360 mg on Day 1 (D1); domvanalimab as an IV at a dose of 1200 mg on D1 and sacituzumab govitecan as an IV at a dose of 10 mg/kg on D1 and 8 D8 of each 21-day cycle until unacceptable toxicity, disease progression, death, discontinuation from the Study treatment for any other reason or End of Study (EoS), whichever occurs first.

Drug: Zimberelimab (AB122); Drug: Domvanalimab (DOM); Drug: Sacituzumab Govitecan (SG)

Interventions

Zimberelimab (AB122) DRUG

Patients will receive zimberelimab as an IV at a dose of 360 mg on D1 of each 21-day cycle until unacceptable toxicity, disease progression, death, discontinuation from the Study treatment for any other reason or End of Study (EoS), whichever occurs first.

zimberelimab, domvanalimab and sacituzumab govitecan

Domvanalimab (DOM) DRUG

Patients will receive domvanalimab as an IV at a dose of 1200 mg on D1 of each 21-day cycle until unacceptable toxicity, disease progression, death, discontinuation from the Study treatment for any other reason or End of Study (EoS), whichever occurs first.

zimberelimab, domvanalimab and sacituzumab govitecan

Sacituzumab Govitecan (SG) DRUG

Patients will receive sacituzumab govitecan as an IV at a dose of 10 mg/kg on D1 and D8 of each 21-day cycle until unacceptable toxicity, disease progression, death, discontinuation from the Study treatment for any other reason or End of Study (EoS), whichever occurs first.

zimberelimab, domvanalimab and sacituzumab govitecan

Eligibility Criteria

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

You may qualify if:

• Female or male participants, regardless of race and/or ethnic group, aged 18 years or older, able to understand and give written informed consent form (ICF).
• Histologically confirmed TNBC per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 criteria, based on local testing performed on the most recent biopsy in the metastatic setting. . Triple-negative status is defined as \<1% expression for estrogen receptor (ER) and progesterone receptor (PgR) and negative for human epidermal growth factor receptor 2 (HER2) (0-1+ by immunohistochemistry or 2+ and negative by in situ hybridization test).
• PD-L1 positive status defined as a CPS ≥ 10 determined by the antibody 22C3 PharmDx assay, based on local testing.
• Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
• Measurable disease according to RECIST v.1.1. Tumor lesions situated in a previously irradiated area are considered measurable if unequivocal progression has been documented in such lesions since radiation.
• No prior systemic therapy for advanced disease. For patients receiving (neo)adjuvant therapy, a disease-free interval of at least 6 months between completion of systemic treatment with curative intent and first documented local or distant disease recurrence is mandatory. Dates of postoperative radiotherapy are not included in this calculation. Prior use of an anti-PD-L1 agent in the curative TNBC setting is permitted.
• Have adequate bone marrow, liver, and renal function.
• Resolution of all acute toxic effects of previously administered agent to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
• Willingness to provide blood and stool samples at the established time points.
• Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before Study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 6 months after the last dose of Study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same period.
• Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening until 6 months after the last administration of the Study drug. Male participants must not donate or bank sperm during this same period.
• ECOG performance status of 0-1.
• Minimum life expectancy of ≥ 12 weeks at screening.

You may not qualify if:

• Inability to comply with Study and follow-up procedures.
• Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol.
• Concomitant participation in a Study with an investigational agent or investigational device within 4 weeks prior to Study enrolment. Participants enrolling in observational studies are eligible.
• Have previously been treated with chemotherapy or immunotherapy in the metastatic setting.
• Have previously been treated with topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor in the curative setting.
• Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases (except those treated with chemotherapy) may participate if they meet the following criteria: stable CNS disease demonstrated by radiographic stability for at least 4 weeks prior to enrollment, all neurologic symptoms have returned to baseline, no evidence of new or enlarging brain metastases, and clinical stability for at least 2 weeks while taking ≤ 10 mg/day of prednisone or its equivalent. However, all participants with carcinomatous meningitis are excluded regardless of clinical stability.
• Have a concurrent malignancy or malignancy within 3 years of Study enrollment except for participants with surgically cured carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer, that are allowed to enroll. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.
• Known allergy or hypersensitivity reaction to any investigational medicinal product (IMP) including zimberelimab, sacituzumab govitecan and domvanalimab or any of their components.
• Requirement for ongoing therapy with any prohibited medications listed in the protocol.
• Have received prior radiotherapy within 2 weeks of start of Study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A two-week washout period is permitted for palliative radiation to non-CNS disease.
• Major surgical procedure or significant traumatic injury within 14 days before the first dose of Study treatment or anticipation of need for major surgery within the course of the Study treatment.
• Have active chronic inflammatory bowel disease (ulcerative colitis/Crohn's disease) or gastrointestinal perforation within 6 months of enrollment.
• Have an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within three months of the Study enrolment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion, post COVID-19 pulmonary fibrosis, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
• Have a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.

Sponsors & Collaborators

• MedSIR: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

zimberelimab; sacituzumab govitecan

Condition Hierarchy (Ancestors)

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

Study Officials

• Tim Robinson, BMBS, PhD

  University of Bristol, Bristol, England (UK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2025
• First Posted: August 21, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): May 28, 2028
• Study Completion (Estimated): December 28, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share