Binimetinib in combination with nivolumab or nivolumab and ipilimumab in patients with previously treated microsatellite-stable metastatic colorectal cancer with RAS mutations in an open-label phase 1b/2 study.

Background: In patients with previously treated RAS-mutated microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), a multicenter open-label phase 1b/2 trial was conducted to define the safety and efficacy of the MEK1/MEK2 inhibitor binimetinib in combination with the immune checkpoint inhibitor (ICI) nivolumab (anti-PD-1) or nivolumab and another ICI, ipilimumab (anti-CTLA4).

Methods: In phase 1b, participants were randomly assigned to Arm 1A (binimetinib 45 mg twice daily [BID] plus nivolumab 480 mg once every 4 weeks [Q4W]) or Arm 1B (binimetinib 45 mg BID plus nivolumab 480 mg Q4W and ipilimumab 1 mg/kg once every 8 weeks [Q8W]) to determine the maximum tolerable dose (MTD) and recommended phase 2 dose (RP2D) of binimetinib. The MTD/RP2D was defined as the highest dosage combination that did not cause medically unacceptable dose-limiting toxicities in more than 35% of treated participants in Cycle 1.

A plain language summary of the PHAROS study: the combination of encorafenib and binimetinib for people with BRAF V600E-mutant metastatic non-small-cell lung cancer.

What Is This Summary About?: This is a summary of the results of a study called PHAROS. This study looked at combination treatment with encorafenib (BRAFTOVI) and binimetinib (MEKTOVI). This combination of medicines was studied in people with metastatic non-small-cell lung cancer (NSCLC).

Encorafenib plus binimetinib in patients with -mutant non-small cell lung cancer: phase II PHAROS study design.

oncogenic driver mutations occur in 1-2% of non-small-cell lung cancers (NSCLCs) and have been shown to be a clinically relevant target. Preclinical/clinical evidence support the efficacy and safety of BRAF and MEK inhibitor combinations in patients with NSCLC with these mutations. We describe the design of PHAROS, an ongoing, open-label, single-arm, phase II trial evaluating the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with metastatic -mutant NSCLC, as first- or second-line treatment.

Factors Influencing Infusion-Related Reactions Following Dosing of Reference Rituximab and PF-05280586, a Rituximab Biosimilar.

Background: Infusion-related reactions (IRRs) are the most common adverse event (AE) associated with infusion of rituximab, an anti-CD20 monoclonal antibody.

Objective: Our objective was to evaluate the impact of dosing/infusion patterns and certain baseline characteristics on IRR occurrence during the first rituximab infusion administered as the biosimilar PF-05280586 (RTX-PF) or reference rituximab sourced from the EU (RTX-EU, MabThera) in patients with CD20+ low-tumor-burden follicular lymphoma.

Patients And Methods: Rituximab (RTX-PF, n=196; RTX-EU, n=198) was administered (375 mg/m) on days 1, 8, 15, and 22 (one cycle), with a follow-up period through 52 weeks.

A Randomized, Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera) in Subjects with Previously Untreated CD20-Positive, Low-Tumor-Burden Follicular Lymphoma (LTB-FL).

Background: Biosimilars are highly similar to the licensed biologic ("reference product"), with no clinically meaningful differences in safety, purity, or potency between the two products.

Objective: This comparative 52-week clinical study evaluated the efficacy, safety, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-05280586 (Ruxience™ [a rituximab biosimilar]) versus rituximab reference product sourced from the EU (MabThera; rituximab-EU).

Patients And Methods: Subjects with CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL) and an Eastern Cooperative Oncology Group performance status 0-1 were randomized (1:1) to PF-05280586 or rituximab-EU (375 mg/m intravenously [once weekly for 4 weeks at days 1, 8, 15, and 22]), stratified using the Follicular Lymphoma International Prognostic Index 2 classification.