A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus)

Abstract

Background:Pembrolizumab (P) is an anti-PD-1 antibody that blocks the interaction between programmed cell death protein 1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumour cells. A phase Ib trial of P plus chemotherapy was undertaken to evaluate the safety and efficacy.Methods:Patients with advanced, metastatic solid tumours were enrolled onto one of six treatment arms. Pembrolizumab was given: with gemcitabine (G), G+docetaxel (D), G+nab-paclitaxel (NP), G+vinorelbine (V) or irinotecan (I) until progression or toxicity, or with liposomal doxorubicin (LD) for up to 15 cycles, progression or toxicity. Safety monitoring and response assessments were conducted.Results:Forty-nine patients were enrolled and treated. The most common adverse events were transaminitis, cytopenias, rash, diarrhoea, fatigue, nausea and vomiting. Arm 2 was closed due to poor accrual. The recommended phase II dose (RP2D) was determined for Arms 1, 3a, 4, 5 and 6. There were eight partial responses across multiple tumour types.Conclusions:Standard dose P can be safely combined with G, G+NP, G+V, I and LD. Efficacy was observed in multiple tumour types and evaluation to determine if response and duration of response are more robust than what would be expected for chemotherapy or immunotherapy alone requires further validation.

Codelivery of Anti‐PD‐1 Antibody and Paclitaxel with Matrix Metalloproteinase and pH Dual‐Sensitive Micelles for Enhanced Tumor Chemoimmunotherapy

“…Aiming at improving the anticancer effect, many other treatment methods have been combined with immunotherapy in pre‐clinical studies or even in clinical trials recently . Chief among them, chemotherapy is regarded as a proper candidate for such combination therapy owing to its effective tumor growth inhibition .…”

“…Aiming at improving the anticancer effect, many other treatment methods have been combined with immunotherapy in pre‐clinical studies or even in clinical trials recently . Chief among them, chemotherapy is regarded as a proper candidate for such combination therapy owing to its effective tumor growth inhibition . More critically, increasing evidences are showing that some chemotherapeutic agents such as anthracyclines and taxanes not only induce the apoptosis of tumor cells, but also cause immunogenic cell death (ICD) to activate immune system .…”

Pembrolizumab in advanced pretreated small cell lung cancer patients with PD-L1 expression: data from the KEYNOTE-028 trial: a reason for hope?

“…PembroPlus trial (NCT02331251) is a phase 1b-2 study that evaluated the role of pembrolizumab in combination with different cytotoxic agents (16 In conclusion, despite the promising signal of efficacy of pembrolizumab in advanced ED-SCLC disease, as highlighted in this small size clinical trial, there is an urgent need for a better understanding. First, finding a better predictive biomarker for a more accurate identification of patients most likely to benefit from anti-PD1 inhibition is of crucial relevance.…”

Immunotherapy: Pancreatic Cancer and Extrahepatic Biliary Tract Cancer

“…In total 11 patients with metastatic PDAC (after first-line chemotherapy or treatment naïve) received chemotherapy in combination with pembrolizumab. Two patients showed a partial remission, 6 patients had a stable disease [25]. Interim results from a phase I trial combining nivolumab plus nab-paclitaxel with or without gemcitabine showed a response in 12 out of 17 patients (5 patients partial remission, 7 patients stable disease) with locally advanced or metastatic PDAC [26].…”