Phase II Study Evaluating the Efficacy and Safety of Ociperlimab in Combination With Tislelizumab and Chemotherapy as First-line Treatment for Participants With Advanced Triple Negative Breast Cancer

NCT ID: NCT05809895

Last Updated: 2023-07-24

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-15
• Study Completion Date: 2029-07-18

Brief Summary

The primary scientific question of interest of this study is whether the combination of ociperlimab, tislelizumab and chemotherapy improves progression-free survival (PFS) compared to the combination of placebo, pembrolizumab and chemotherapy as first-line therapy for adult men and women with advanced triple negative breast cancer (TNBC) whose tumors express programmed death ligand 1 (PD - L1) [combined positive score (CPS) ≥10], regardless of study treatment discontinuation or start of new anti-neoplastic therapy.

Detailed Description

This is a randomized, double-blind, placebo-controlled, multicenter, Phase II study evaluating the efficacy and safety of ociperlimab in combination with tislelizumab and chemotherapy as first-line treatment for participants with advanced TNBC whose tumors express PD-L1 (CPS ≥ 10).

Additionally, the efficacy and safety of the triple combination (ociperlimab + tislelizumab + chemotherapy) will be assessed in Arm D (a separate single-arm, open-label cohort) in 30 participants with advanced TNBC whose tumors express PD-L1 (CPS ≥ 1 to < 10).

Study treatment will continue until the participant experiences one of the following: disease progression per investigator's assessment by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, unacceptable toxicity, pregnancy, treatment is discontinued at the discretion of the investigator or participant, start of a new antineoplastic therapy, withdrawal of consent, lost to follow-up, death, or study is terminated by the sponsor.

Conditions

Triple Negative Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10)

Participants with a PD-L1 CPS ≥ 10 will receive after randomization ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.

Group Type: EXPERIMENTAL

Ociperlimab

Intervention Type: DRUG

900 mg intravenously (IV) every 3 weeks (Q3W)

Tislelizumab

Intervention Type: DRUG

200 mg intravenously (IV) Q3W

Paclitaxel

Intervention Type: DRUG

90 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Nab-paclitaxel

Intervention Type: DRUG

100 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Carboplatin

Intervention Type: DRUG

AUC 2 intravenously (IV) on Days 1 and 8 every 21 days

Gemcitabine

Intervention Type: DRUG

1000 mg/m2 intravenously (IV) on Days 1 and 8 every 21 days

Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10)

Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + pembrolizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

90 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Nab-paclitaxel

Intervention Type: DRUG

100 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Carboplatin

Intervention Type: DRUG

AUC 2 intravenously (IV) on Days 1 and 8 every 21 days

Placebo

Intervention Type: DRUG

normal saline intravenously (IV) Q3W

Pembrolizumab

Intervention Type: DRUG

200 mg intravenously (IV) Q3W

Gemcitabine

Intervention Type: DRUG

1000 mg/m2 intravenously (IV) on Days 1 and 8 every 21 days

Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10)

Participants with a PD-L1 CPS ≥ 10 will receive after randomization placebo + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.

Group Type: ACTIVE_COMPARATOR

Tislelizumab

Intervention Type: DRUG

200 mg intravenously (IV) Q3W

Paclitaxel

Intervention Type: DRUG

90 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Nab-paclitaxel

Intervention Type: DRUG

100 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Carboplatin

Intervention Type: DRUG

AUC 2 intravenously (IV) on Days 1 and 8 every 21 days

Placebo

Intervention Type: DRUG

normal saline intravenously (IV) Q3W

Gemcitabine

Intervention Type: DRUG

1000 mg/m2 intravenously (IV) on Days 1 and 8 every 21 days

Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)

Exploratory arm: Participants with a PD-L1 CPS ≥ 1 to \< 10 will receive ociperlimab + tislelizumab + chemotherapy. The choice of one of three chemotherapy options is at the discretion of the investigator provided that it is either: (1) paclitaxel, (2) nab-paclitaxel, or (3) gemcitabine plus carboplatin.

Group Type: OTHER

Ociperlimab

Intervention Type: DRUG

900 mg intravenously (IV) every 3 weeks (Q3W)

Tislelizumab

Intervention Type: DRUG

200 mg intravenously (IV) Q3W

Paclitaxel

Intervention Type: DRUG

90 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Nab-paclitaxel

Intervention Type: DRUG

100 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Carboplatin

Intervention Type: DRUG

AUC 2 intravenously (IV) on Days 1 and 8 every 21 days

Gemcitabine

Intervention Type: DRUG

1000 mg/m2 intravenously (IV) on Days 1 and 8 every 21 days

Interventions

Ociperlimab

900 mg intravenously (IV) every 3 weeks (Q3W)

Intervention Type: DRUG

Tislelizumab

200 mg intravenously (IV) Q3W

Intervention Type: DRUG

Paclitaxel

90 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Intervention Type: DRUG

Nab-paclitaxel

100 mg/m2 intravenously (IV) on Days 1, 8 and 15 every 28 days

Intervention Type: DRUG

Carboplatin

AUC 2 intravenously (IV) on Days 1 and 8 every 21 days

Intervention Type: DRUG

Placebo

normal saline intravenously (IV) Q3W

Intervention Type: DRUG

Pembrolizumab

200 mg intravenously (IV) Q3W

Intervention Type: DRUG

Gemcitabine

1000 mg/m2 intravenously (IV) on Days 1 and 8 every 21 days

Intervention Type: DRUG

Other Intervention Names

WCD118; VDT482; MK-3475

Eligibility Criteria

Inclusion Criteria

• Participant has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy, or metastatic (stage IV)) TNBC
• Participant has completed systemic treatment for Stage I-III breast cancer, if indicated, and ≥ 6 months have elapsed between the completion of systemic treatment with curative intent and disease recurrence
• A recently or newly obtained tumor biopsy from a metastatic site must be provided for determination of PD-L1 expression using the PD-L1 IHC 22C3 assay by a Novartis designated central laboratory, prior to study randomization. If a result of PD-L1 expression assessed by a PD-L1 IHC 22C3 pharmDx test in a local laboratory is available, this can serve as PD-L1 status confirmation. For Arms A, B and C participants must have PD-L1 positive tumors with CPS≥ 10. For Arm D, participants must have PD-L1 positive tumors with CPS ≥ 1 to < 10.
• Participant has measurable disease, i.e., at least one measurable lesion per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation)
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participant has life expectancy ≥ 12 weeks from the start of study treatment

Exclusion Criteria

• Participant has received prior treatment with immunotherapy in the metastatic setting, or anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) therapy in any setting
• History of severe hypersensitivity to any of the study drugs (i.e. monoclonal antibodies, gemcitabine, carboplatin, nab-paclitaxel, paclitaxel) or its excipients or to drugs of similar chemical classes
• Participant with inflammatory breast cancer at screening
• Participant has central nervous system (CNS) involvement which was not previously treated and/or was newly detected at screening. Previously treated CNS involvement must fulfill the following criteria to be eligible for the trial:

1. Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of the study and

2. CNS tumor is clinically stable at the time of screening, and

3. Participant is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases

• Participant has an active autoimmune diseases or history of autoimmune diseases that may relapse
• Participant has not recovered from all toxicities related to prior anticancer therapies to National Cancer Institute (NCI) CTCAE version 5.0 Grade ≤1. Exception to this criterion: participants with any grade of alopecia are allowed to enter the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Other Identifiers

2022-503099-99-00

Identifier Type: OTHER

Identifier Source: secondary_id

CWCD118B12201

Identifier Type: -

Identifier Source: org_study_id