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Posted by on Sep 18, 2022 in Colorectal cancer | 0 comments

In a nutshell

This study evaluated the effectiveness and safety of adding PolyPepI1018 peptide vaccine to fluoropyrimidine/bevacizumab (Avastin) maintenance therapy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). The data showed that PolyPEPI1018 added to maintenance therapy was safe and associated with specific immune responses and antitumor activity in these patients.

Some background

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. Some patients do not report symptoms with the initial tumor. These patients are often only diagnosed when the cancer has spread to other areas (metastatic CRC). The standard treatment for these patients is chemotherapy (CT) combined with targeted therapy.

Bevacizumab is a type of targeted therapy. It works by stopping tumors from forming new blood vessels and spreading. Studies have shown that bevacizumab improves the outcomes of patients with mCRC when added to chemotherapy like fluoropyrimidines (such as 5-fluorouracil).

Although CT is standard-of-care for mCRC, immunotherapy has no role in microsatellite stable (MSS) mCRC. MSS means that the tumors have many mutations (genetic abnormalities). MSS tumors generally block the immune system and do not respond to immunotherapies. 

PolyPEPI1018 peptide vaccine is used to immunize against proteins present on the surface of tumor cells. This vaccine can activate the body's immune cells, called T cells. T cells fight infections and can also kill cancer cells. However, the effectiveness and safety of adding PolyPepI1018 to fluoropyrimidine CT/bevacizumab maintenance therapy in patients with MSS mCRC are unknown.

Methods & findings

This study involved 11 patients with MSS mCRC. All patients received PolyPEPI1018 combined with fluoropyrimidine CT/bevacizumab. 5 patients received a single dose of the vaccine and 6 patients received up to three doses of PolyPEPI1018 every 12 weeks. The patients were followed up for 12 weeks after the last vaccination.

80% of patients had CD8+ T-cell responses against more than 3 tumor-associated antigens. Increased density of tumor-infiltrating lymphocytes were detected after treatment for 3 of 4 patients’ liver biopsies, combined with increased expression of immune-related gene signatures.

3 patients had an objective response (complete or partial disappearance of cancer cells) and 2 patients qualified for curative surgery. By the end of the study, 3 patients (27.3%) had a partial response, 4 patients (36.3%) had stable disease (the tumor remained the same) and 4 patients (36.3%) had progressive disease. 

The average survival without cancer worsening for patients who received multiple doses was 12.5 months compared to 4.6 months in patients who received a single dose.

PolyPEPI1018 vaccination was safe and well-tolerated. No vaccine-related serious side effects were observed in the patients. Infusion-related side effects were reported such as swelling, redness, and itching. Most of these were noted by the patients as "mild".

The bottom line

This study concluded that PolyPEPI1018 added to maintenance chemotherapy was safe and associated with specific immune responses and antitumor activity in patients with MSS mCRC.

The fine print

The sample size was very small as this was a Phase Ib study. This study was funded by Treos Bio. Ltd., the manufacturer of PolyPepI1018. The study did not have a control group. Further larger randomized studies are needed to further evaluate the safety and effectiveness of this treatment. 

Published By :

Clinical Cancer Research

Date :

Apr 26, 2022

Original Title :

Safety and activity of PolyPEPI1018 combined with maintenance therapy in metastatic colorectal cancer: an open-label, multicenter, phase 1b study.

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