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

NCT05809895 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: CWCD118B122012022-503099-99-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Triple Negative Breast Cancer

Keywords

TNBC; Triple Negative Breast Cancer; PD-L1; Ociperlimab; Tislelizumab; WCD118 (BGB-A1217); VDT482 (BGB-A317); Pembrolizumab; Carboplatin; Gemcitabine; Paclitaxel; Nab-paclitaxel; TIGIT; Combination immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) based on investigator assessment using RECIST 1.1 criteria in Arm A and B

  PFS is defined as the time from the date of randomization to the date of first documented progression or death due to any cause. The comparison of PFS between Arm A and Arm B will be provided

  From randomization to date of disease progression or death, assessed up to approximately 32 months after first randomization

Secondary Outcomes (15)

• Overall Survival (OS) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C

  From randomization to death, assessed up to approximately 32 months after first randomization

• Overall Response Rate (ORR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C

  Up to approximately 32 months after first randomization

• Clinical benefit rate (CBR) with confirmed response in Arm A, B and C

  Approximately 32 months after first randomization

• Time to response (TTR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C

  From randomization to first documented response, assessed up to approximately 32 months after first randomization

• Duration of Response (DOR) based on investigator assessment using RECIST 1.1 criteria in Arm A, B and C

  From first documented response to disease progression or death, assessed up to approximately 32 months after first randomization

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: Ociperlimab; Drug: Tislelizumab; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Carboplatin; Drug: Gemcitabine

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

ACTIVE COMPARATOR

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.

Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Carboplatin; Drug: Placebo; Drug: Pembrolizumab; Drug: Gemcitabine

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

ACTIVE COMPARATOR

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.

Drug: Tislelizumab; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Carboplatin; Drug: Placebo; Drug: Gemcitabine

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

OTHER

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.

Drug: Ociperlimab; Drug: Tislelizumab; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Carboplatin; Drug: Gemcitabine

Interventions

Ociperlimab DRUG

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

Also known as: WCD118

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

Tislelizumab DRUG

200 mg intravenously (IV) Q3W

Also known as: VDT482

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

Paclitaxel DRUG

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

Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10); Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10); Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10); Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)

Nab-paclitaxel DRUG

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

Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10); Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10); Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10); Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)

Carboplatin DRUG

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

Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10); Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10); Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10); Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)

Placebo DRUG

normal saline intravenously (IV) Q3W

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

Pembrolizumab DRUG

200 mg intravenously (IV) Q3W

Also known as: MK-3475

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

Gemcitabine DRUG

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

Arm A: ociperlimab+tislelizumab+chemotherapy (PD-L1 CPS ≥ 10); Arm B: placebo + pembrolizumab + chemotherapy (PD-L1 CPS ≥ 10); Arm C: placebo + tislelizumab + chemotherapy (PD-L1 CPS ≥ 10); Arm D: ociperlimab + tislelizumab + chemotherapy (PD-L1 CPS score ≥ 1 to < 10)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:
• Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥ 28 days prior to the start of the study and
• CNS tumor is clinically stable at the time of screening, and
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

tislelizumab; Paclitaxel; 130-nm albumin-bound paclitaxel; Carboplatin; pembrolizumab; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants will be randomized to Arms A, B and C in a double-blind manner Participants will be enrolled in Arm D in an open-label manner
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2023
• First Posted: April 12, 2023
• Study Start: September 15, 2023
• Primary Completion (Estimated): July 17, 2029
• Study Completion (Estimated): July 18, 2029
• Last Updated: July 24, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share