Four Positive Studies of Keytruda Highlight Its Potential as a New Standard for First-Line Treatment of MSI-H Colorectal Cancer

Source: Medical Perspective

The 2020 American Society of Clinical Oncology (ASCO) Annual Meeting will be held from May 29 to May 31, U.S. Eastern Time. Today, MSD, Eisai, and Celltrion Healthcare respectively announced that they will present the results of four clinical studies on MSD’s PD-1 inhibitor Keytruda (pembrolizumab) as monotherapy or in combination with other drugs at the ASCO Annual Meeting.

Keytruda Poised to Become New Standard of Care for First-Line Treatment of MSI-H Metastatic Colorectal Cancer

MSD will present the results of the KEYNOTE-177 study for the first time at ASCO. KEYNOTE-177 is a randomized, open-label, Phase 3 clinical trial designed to compare the efficacy of first-line treatment with the PD-1 monoclonal antibody Keytruda versus standard-of-care chemotherapy in patients with unresectable or metastatic colorectal cancer characterized by high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The primary endpoints of the study are progression-free survival (PFS) and overall survival (OS).

This pivotal study demonstrated that Keytruda monotherapy reduced the risk of disease progression or death by 40%. The median progression-free survival (PFS) in the Keytruda monotherapy group was 16.5 months, more than double that of the standard-of-care chemotherapy group (8.2 months). Furthermore, the two-year PFS rate was substantially higher in the Keytruda group compared to the chemotherapy group (48% vs. 19%). Additionally, the objective response rate (ORR) was 43.8% in the Keytruda group versus 33.1% in the chemotherapy group. Durable responses lasting at least two years were observed in 83% of patients treated with Keytruda, compared to only 35% in the chemotherapy group.

According to the press release, KEYNOTE-177 is the first head-to-head Phase 3 clinical trial to yield positive results in comparing PD-1 antibodies with chemotherapy as first-line treatment for MSI-H metastatic colorectal cancer. Data from the KEYNOTE-177 study indicate that Keytruda monotherapy has the potential to become the new standard of care for first-line treatment of patients with MSI-H metastatic colorectal cancer. The study will continue to evaluate the other primary endpoint, overall survival.

Keytruda Triple Therapy Shows Significant Efficacy as First-Line Treatment for HER2-Positive Gastric Cancer

Celltrion Healthcare of South Korea announced that it will present study data at ASCO on the first-line treatment of HER2-positive advanced gastric cancer with Keytruda in combination with Herzuma (a trastuzumab biosimilar) and chemotherapy. This Phase 1b/2 trial, named PANTHERA, aims to evaluate the efficacy and safety of pembrolizumab combined with Herzuma, capecitabine, and cisplatin as first-line therapy for patients with HER2-positive advanced gastric cancer (AGC). A total of 43 patients received treatment, with a median follow-up period of 18 months.

Latest data show that this combination therapy is effective in treating patients with HER2-positive advanced gastric cancer. Significant tumor shrinkage was observed regardless of PD-L1 status, with a rate of marked tumor reduction of 95.3%. The objective response rate (ORR) was 76.7%, including complete response (CR) in 16.3% of patients and partial response (PR) in 60.5%. The disease control rate (DCR) was 97.7%.

For secondary endpoints, the median PFS was 8.6 months, the median OS was 19.3 months, and the median duration of response (DoR) was 10.8 months. Furthermore, no new safety signals were observed by the investigators.

“According to the study, first-line treatment of HER2-positive advanced gastric cancer (AGC) patients with this triple regimen leads to clinically meaningful improvements (significant tumor shrinkage), regardless of PD-L1 status,” stated Professor Sun Young Rha from Yonsei University College of Medicine and the Yonsei Cancer Center. “This is the first time that the triple combination of Herzuma, immunotherapy, and chemotherapy has delivered a true benefit to patients in the first-line setting.”

Keytruda in Combination with Lenvatinib Achieves Positive Results in Hepatocellular Carcinoma and Renal Cell Carcinoma

MSD and Eisai Jointly Announce Latest Data from Two Clinical Studies Evaluating MSD’s PD-1 Antibody Keytruda and Eisai’s Oral Multi-Receptor Tyrosine Kinase Inhibitor Lenvima (Lenvatinib) to Be Presented at ASCOThe latest results from these two studies demonstrated that the combination therapy of Keytruda and Lenvima achieved clinically meaningful objective response rates in patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic therapy, as well as in patients with metastatic clear cell renal cell carcinoma (RCC) who had progressed after treatment with immune checkpoint inhibitors.

KEYNOTE-524/Study 116 Trial

KEYNOTE-524/Study 116 is an open-label, single-arm Phase 1b clinical trial designed to evaluate the efficacy of the combination therapy of Keytruda and Lenvima in 100 patients with unresectable hepatocellular carcinoma (HCC) who have not previously received systemic treatment. The primary endpoints are objective response rate (ORR) and duration of response (DOR). Secondary endpoints include progression-free survival, time to progression (TTP), and overall survival.

As of the data cutoff date (October 31, 2019), the median follow-up time was 10.6 months, and 37 patients were still receiving study treatment (Keytruda + Lenvima group: n=34; Lenvima monotherapy group: n=3). The median duration of Keytruda + Lenvima combination therapy was 7.9 months.

The ORR assessed by RECIST v1.1 criteria was 36%, with a complete response rate of 1% (n=1) and a partial response rate of 35% (n=35); the median DOR was 12.6 months. The ORR assessed by RECIST criteria was 46% (n=46), with a complete response rate of 11% (n=11) and a partial response rate of 35% (n=35); the median DOR was 8.6 months.

KEYNOTE-146/Study 111 Trial

KEYNOTE-146/study 111 is an open-label, single-arm phase 1b/2 trial designed to evaluate the efficacy of the combination therapy of Keytruda and Lenvima in patients with certain solid tumors. The results from the phase 2 RCC cohort of this study were derived from 104 patients with metastatic clear cell renal cell carcinoma who experienced disease progression following treatment with PD-1/PD-L1 immune checkpoint inhibitors, as assessed per RECIST v1.1 criteria. In the study, patients received intravenous Keytruda 200 mg every three weeks in combination with oral Lenvima 20 mg daily until unacceptable toxicity or disease progression occurred.

The results showed that the ORR assessed by irRECIST criteria was 55%, with a partial response rate of 55%, a stable disease rate of 36%, and a progressive disease rate of 5% (5% not evaluable). The median DOR was 12 months, the median PFS was 11.7 months, and the 12-month PFS rate was 45%. The median OS was not reached (NR), and the 12-month OS rate was 77%. The ORR assessed by RECIST v1.1 criteria was 52%, with a partial response rate of 52%, a stable disease rate of 38%, and a progressive disease rate of 6% (5% not evaluable). The median DOR was 12 months. The median PFS was 11.3 months, and the 12-month PFS rate was 44%.

Notably, the combination therapy of Keytruda and Lenvima was approved by the U.S. FDA last September for the treatment of patients with specific advanced endometrial cancer.

References

[1] Merck’s KEYTRUDA® (pembrolizumab) Superior to Standard of Care Chemotherapy in Patients with MSI-H Colorectal Cancer. Retrieved May 28, 2020, from https://www.mrknewsroom.com/news-release/asco/mercks-keytruda-pembrolizumab-superior-standard-care-chemotherapy-patients-msi-h-c

[2] KEYTRUDA® (pembrolizumab) plus LENVIMA® (lenvatinib) Combination Demonstrated Clinically Meaningful Tumor Response Rates in Unresectable Hepatocellular Carcinoma and Advanced Renal Cell Carcinoma.Retrieved May 28, 2020, from https://www.mrknewsroom.com/news-release/asco/keytruda-pembrolizumab-plus-lenvima-lenvatinib-combination-demonstrated-clinically

[3]New data show first-line triplet regimen of pembrolizumab, Herzuma® (biosimilar trastuzumab) and chemotherapy are effective in treatment of HER2-positive advanced gastric cancer. Retrieved May 28, 2020, from https://www.businesswire.com/news/home/20200528005553/en

(Original Title: Four Studies on “Keytruda” Yield Positive Results, Poised to Become New Standard of Care for First-Line Treatment of MSI-H Colorectal Cancer | Today at ASCO)

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