Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site VSports app下载. .

Https

The site is secure V体育官网. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. .

Clinical Trial
. 2022 Mar 11;27(3):198-209.
doi: 10.1093/oncolo/oyab046.

VSports最新版本 - A Randomized Phase II Trial of mFOLFOX6 + Bevacizumab Alone or with AdCEA Vaccine + Avelumab Immunotherapy for Untreated Metastatic Colorectal Cancer

Jason M Redman  1   2 , Yo-Ting Tsai  2 , Benjamin A Weinberg  3 , Renee N Donahue  2 , Shruti Gandhy  1 , Margaret E Gatti-Mays  2 , Houssein Abdul Sater  1 , Marijo Bilusic  1 , Lisa M Cordes  1 , Seth M Steinberg  4 , Jennifer L Marte  1 , Caroline Jochems  2 , Sunnie S Kim  5 , John L Marshall  3 , Sheri McMahon  1 , Erica Redmond  1 , Jeffrey Schlom  2 , James L Gulley  1 , Julius Strauss  2
Affiliations
Clinical Trial

A Randomized Phase II Trial of mFOLFOX6 + Bevacizumab Alone or with AdCEA Vaccine + Avelumab Immunotherapy for Untreated Metastatic Colorectal Cancer

Jason M Redman et al. Oncologist. .

Abstract

Background: FOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine. VSports手机版.

Methods: Patients with untreated MSS mCRC enrolled to a lead-in arm assessing safety of SOC + immuno-oncology agents (IO). Next, patients were randomized to SOC or SOC + IO. The primary endpoint was progression-free survival (PFS). Multiple immune parameters were analyzed V体育安卓版. .

Results: Six patients enrolled to safety lead-in, 10 randomized to SOC, and 10 to SOC + IO. There was no difference in median PFS comparing SOC versus SOC + IO (8. 8 months (95% CI: 3. 3-17. 0 months) versus 10 V体育ios版. 1 months (95% CI: 3. 6-16. 1 months), respectively; hazard ratio 1. 061 [P = . 91; 95% CI: 0. 380-2. 966]). The objective response rate was 50% in both arms. Of patients analyzed, most (8/11) who received SOC + IO developed multifunctional CD4+/CD8+ T-cell responses to cascade antigens MUC1 and/or brachyury, compared to 1/8 who received SOC alone (P = . 020). We detected post-treatment changes in immune parameters that were distinct to the SOC and SOC + IO treatment arms. Accrual closed after an unplanned analysis predicted a low likelihood of meeting the primary endpoint. .

Conclusions: SOC + IO generated multifunctional MUC1- and brachyury-specific CD4+/CD8+ T cells despite concurrent chemotherapy VSports最新版本. Although a tumor-directed immune response is necessary for T-cell-mediated antitumor activity, it was not sufficient to improve PFS. Adding agents that increase the number and function of effector cells may be required for clinical benefit. .

Keywords: Avelumab; FOLFOX; colorectal cancer; combination immunotherapy; immune response; therapeutic vaccine V体育平台登录. .

PubMed Disclaimer

"V体育安卓版" Figures

Figure 1.
Figure 1.
Enrollment schema: Patients were first enrolled on a safety lead-in arm. After the safety of the SOC + IO combination was established, patients were randomized to SOC (Arm A) or SOC + IO (Arm B). After completion of induction mFOLFOX-based treatment, patients received maintenance capecitabine or 5-fluorouracil plus bevacizumab. Patients were treated until progression. Patients randomized to SOC were given the option to cross over to the SOC + IO regimen on progression if clinically appropriate. SOC, standard of care; SOC + IO, standard of care plus immuno-oncology agents.
Figure 2.
Figure 2.
Progression-free survival in months since enrollment for patients treated with SOC or SOC plus immunotherapy (SOC + IO). SOC, standard of care; SOC + IO, SOC plus immuno-oncology agents.
Figure 3.
Figure 3.
Outcomes: Swimmer plot depicts the time of partial response, crossover (if applicable), and ongoing responses at the time of analysis in relation to months on treatment. Treatment regimen and BRAF V600E mutational status are indicated by color.
Figure 4.
Figure 4.
Immune parameters associated with clinical response. Immune parameters at baseline (A-F) and early changes after 1 month of therapy (G-M) were evaluated in each arm (A-B, G-K) and in a pool of patients from both arms (C-F, L-M). Immune parameters that correlate with the likelihood of BOR of SD vs. BOR of PR are shown. BOR, best overall response; DP, double-positive; EM, effector memory; PR, partial response; SD, stable disease.
See this image and copyright information in PMC

References

    1. National Cancer Institute Surveillance, Epiemiology, and End Results Program. National Institutes of Health. Available at https://seer.cancer.gov. Accessed 20 April 2021.
    1. Grothey A, Sugrue MM, Purdie DM, et al. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol. 2008;26(33):5326-5334. 10.1200/JCO.2008.16.3212 - DOI - PubMed
    1. Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA. 2017;317(23):2392-2401. 10.1001/jama.2017.7105 - DOI - PMC - PubMed
    1. Andre T, Shiu K, Kim T, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 Study. J Clin Oncol. 2020;38(suppl 18): Abstract LBA4.
    1. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-2520. 10.1056/NEJMoa1500596 - DOI - PMC - PubMed

"V体育安卓版" Publication types

MeSH terms

V体育官网 - Substances