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 (AdvanTIG-211)

Novartis

Status and phase

Withdrawn

Phase 2

Conditions

Triple Negative Breast Cancer

Treatments

Drug: Gemcitabine

Drug: Carboplatin

Drug: Paclitaxel

Drug: Nab-paclitaxel

Drug: Ociperlimab

Drug: Placebo

Drug: Pembrolizumab

Drug: Tislelizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT05809895

2022-503099-99-00 (Other Identifier)

CWCD118B12201

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Key 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

Key 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

Other inclusion/exclusion criteria may apply

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

0 participants in 4 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Tislelizumab

Drug: Carboplatin

Drug: Paclitaxel

Drug: Ociperlimab

Drug: Gemcitabine

Drug: Nab-paclitaxel

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

Active Comparator group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Carboplatin

Drug: Paclitaxel

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Placebo

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

Active Comparator group

Description:

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.

Treatment:

Drug: Tislelizumab

Drug: Carboplatin

Drug: Paclitaxel

Drug: Gemcitabine

Drug: Nab-paclitaxel

Drug: Placebo

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

Other group

Description:

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.

Treatment:

Drug: Tislelizumab

Drug: Carboplatin

Drug: Paclitaxel

Drug: Ociperlimab

Drug: Gemcitabine

Drug: Nab-paclitaxel