A phase I/Ib study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer

Kim, Richard D.; Kővári, Bence; Martínez, María Carmen Riesco; Xie, Hao; Şahin, Ibrahim Halil; Mehta, Rutika; Strosberg, Jonathan R.; Imanirad, Iman; Ghayouri, Masoumeh; Kim, Young‐Chul; Kim, Dae Won

doi:10.1016/j.ejca.2022.03.026

Cited by 42 publications

(36 citation statements)

References 23 publications

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“…Overall, 10 percent of the 40 evaluable patients showed a partial response, and 53 percent attained stable disease. In this clinical experiment, the researchers found that the expression of Treg in tumor tissue was negatively correlated with the FPS of patients (9). The results of the REGONIVO trial mentioned above are better than this clinical trial.…”

Section: Clinical Trials Of Combined Therapymentioning

confidence: 81%

“…This study demonstrated that regorafenib may overcome anti-PD-1 treatment resistance, and the combination of regorafenib with anti-PD-1 therapy has promising therapeutic potential. In addition, the combination therapy also showed good efficacy and tolerable safety in the treatment of mismatch repair proficient (pMMR) CRC (9). In this phase IB study, 52 patients were recruited to receive the regorafenib and nivolumab combination.…”

Section: Clinical Trials Of Combined Therapymentioning

confidence: 99%

“…Recent studies have shown that regorafenib can optimize the efficacy of anti-PD-1/PD-L1 treatment. Regorafenib combined with nivolumab showed good efficacy and tolerable safety in the treatment of CRC (9). Therefore, regorafenib combined with ICIs therapy may be a promising approach for cancer therapy.…”

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confidence: 99%

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Immunomodulatory effects of regorafenib: Enhancing the efficacy of anti-PD-1/PD-L1 therapy

et al. 2022

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Anti-PD-1/PD-L1 therapy has shown significant benefits in the treatment of a variety of malignancies. However, not all cancer patients can benefit from this strategy due to drug resistance. Therefore, there is an urgent need for methods that can effectively improve the efficacy of anti-PD-1/PD-L1 therapy. Combining anti-PD-1/PD-L1 therapy with regorafenib has been demonstrated as an effective method to enhance its therapeutic effect in several clinical studies. In this review, we describe common mechanisms of resistance to anti-PD-1/PD-L1 therapy, including lack of tumor immunogenicity, T cell dysfunction, and abnormal expression of PD-L1. Then, we illustrate the role of regorafenib in modifying the tumor microenvironment (TME) from multiple aspects, which is different from other tyrosine kinase inhibitors. Regorafenib not only has immunomodulatory effects on various immune cells, but can also regulate PD-L1 and MHC-I on tumor cells and promote normalization of abnormal blood vessels. Therefore, studies on the synergetic mechanism of the combination therapy may usher in a new era for cancer treatment and help us identify the most appropriate individuals for more precise treatment.

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Section: Clinical Trials Of Combined Therapymentioning

confidence: 81%

Section: Clinical Trials Of Combined Therapymentioning

confidence: 99%

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Immunomodulatory effects of regorafenib: Enhancing the efficacy of anti-PD-1/PD-L1 therapy

et al. 2022

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“…Likewise, encouraging anti-tumour activities were observed in a phase I dose escalation clinical trial (REGONIVO) that tested the combination of regorafenib with nivolumab (anti-PD-1 antibody) [52]. However, subsequent studies investigating combinations of regorafenib with ICIs indicated limited clinical benefit [53][54][55][56]. No randomized data have been generated so far that prove the added value of the combination regimen over standard treatment.…”

Section: Tkis In Combination Therapiesmentioning

confidence: 99%

Lost in translation: Revisiting the use of tyrosine kinase inhibitors in colorectal cancer

Iyer¹,

Erp²,

Tauriello³

et al. 2022

Cancer Treatment Reviews

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“…However, the encouraging results of the REGONIVO were not reproduced in the following series of clinical practice. A phase I/Ib study (NCT03712943) treated 52 pMMR CRC patients with a combination of regorafenib and nivolumab ( 53 ).Only 10% of the patients had partial remission, 2.5% had confirmed remission, 53% were stable with a disease control rate of 63%, showing a limited anticancer activity of this therapy in pMMR CRC. This result could be explained by the differences in the patient populations of the two study.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immunotherapies catering to the unmet medical need of cold colorectal cancer

Yuan

Gao

et al. 2022

Front. Immunol.

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As a common malignant tumor of gastrointestinal tract, the incidence of colorectal cancer (CRC) has gradually increased in recent years. In western developed countries, it has even become the second largest malignant tumor next to lung cancer. Immunotherapy is a hot topic in the field of cancer therapy, including immune checkpoint blockade (ICB), adoptive cell therapy (ACT), cancer vaccines and cytokines, aiming to improve the ability of the immune system to recognize, target and eliminate cancer cells. However, cold CRC, which accounts for a high proportion of CRC, is not so reactive to it. The development of immunotherapy to prevent cancer cells from forming “immune escape” pathways to the immune system in cold CRC, has been under increasing study attention. There is proof that an organic combination of radiotherapy, chemotherapy, and several immunotherapies can considerably boost the immune system’s capacity to eradicate tumor cells. In this review, we summarized the role of immunotherapy in colorectal cancer. In addition, we propose a breakthrough and strategy to improve the role of immunotherapy in cold CRC based on its characteristics.

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A phase I/Ib study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer

Cited by 42 publications

References 23 publications

Immunomodulatory effects of regorafenib: Enhancing the efficacy of anti-PD-1/PD-L1 therapy

Immunomodulatory effects of regorafenib: Enhancing the efficacy of anti-PD-1/PD-L1 therapy

Lost in translation: Revisiting the use of tyrosine kinase inhibitors in colorectal cancer

Immunotherapies catering to the unmet medical need of cold colorectal cancer

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