Merck announces positive results from phase KEYNOTE-355 trial of anti-PD-1 therapy Keytruda in combo with chemotherapy to treat mTNBC
Merck announced positive results from the phase 3 KEYNOTE-355 trial investigating Keytruda, Merck’s anti-PD-1 therapy, in combination with chemotherapy as first-line treatment in patients with metastatic triple-negative breast cancer (mTNBC). In patients whose tumors expressed PD-L1 with Combined Positive Score (CPS) =10, Keytruda plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 35% (HR = 0.65 [95% CI, 0.49-0.86], p=0.0012) and improving PFS to a median of 9.7 months compared to 5.6 months for those receiving chemotherapy alone. In patients whose tumors expressed PD-L1 with CPS =1, Keytruda plus chemotherapy improved PFS versus chemotherapy alone (median PFS = 7.6 months versus 5.6 months; HR = 0.74 [95% CI, 0.61-0.90], p=0.0014), however these results did not meet statistical significance. As previously announced, the trial will continue without changes to evaluate the other dual primary endpoint of overall survival (OS).
“The progression-free survival results observed in KEYNOTE-355 have the potential to impart real change for certain patients with metastatic triple-negative breast cancer in the first-line setting,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Merck is committed to evaluating innovative treatment approaches, anchored by Keytruda, across multiple settings and stages of breast cancer. We are encouraged by the positive results from the phase 3 KEYNOTE-355 and neoadjuvant/adjuvant KEYNOTE-522 studies, which demonstrate the potential of Keytruda in combination with chemotherapy for the treatment of triple-negative breast cancer.”
“There is a significant need for treatment regimens that can help women with metastatic triple-negative breast cancer, an aggressive disease,” said Dr. Javier Cortes, Head Breast Cancer program, IOB Institute of Oncology, Quironsalud Group. “The results of this study, demonstrate that if approved, Keytruda in combination with chemotherapy may offer certain women a new option for first-line treatment.”
These results are being presented as an oral abstract session of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline.
The Keytruda breast cancer clinical development program encompasses several internal and external collaborative studies. In addition to KEYNOTE-355, in TNBC these include the ongoing registration-enabling studies KEYNOTE-242 and KEYNOTE-522.
KEYNOTE-355 is a randomized, double-blinded, phase 3 trial evaluating Keytruda in combination with one of three different chemotherapies compared with placebo plus one of the three chemotherapy regimens for the treatment of locally recurrent inoperable or mTNBC that has not been previously treated with chemotherapy in the metastatic setting. The dual primary endpoints are PFS and OS in patients whose tumors expressed PD-L1 (CPS =1 and CPS =10) and in all participants (intention-to-treat [ITT] population). The secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and safety.
KEYNOTE-355 enrolled 847 patients who were randomized 2:1 to receive Keytruda (200 mg every 3 weeks) plus chemotherapy (investigator’s choice of nab-paclitaxel, paclitaxel or gemcitabine/carboplatin); or placebo plus nab-paclitaxel, paclitaxel or gemcitabine/carboplatin. Among enrolled patients in each treatment group, approximately 75% had tumors expressing PD-L1 with CPS =1 (n = 425/566 for Keytruda plus chemotherapy; n = 211/281 for chemotherapy alone) and approximately 38% had had tumors expressing PD-L1 with CPS =10 (n = 220/566 for KEYTRUDA plus chemotherapy; n = 103/281 for chemotherapy alone).
As of data cut-off for this interim analysis (December 11, 2019), median time from randomization to data cut-off was 25.9 months for Keytruda plus chemotherapy and 26.3 months for chemotherapy alone. Keytruda plus chemotherapy significantly improved PFS versus chemotherapy alone in patients whose tumors expressed PD-L1 with CPS =10 (HR = 0.65 [95% CI, 0.49-0.86], p=0.0012). In patients whose tumors expressed PD-L1 with CPS =1, statistical significance for Keytruda plus chemotherapy was not met, but Keytruda plus chemotherapy improved PFS in this patient population versus chemotherapy alone (median PFS = 7.6 months versus 5.6 months; HR = 0.74 [95% CI, 0.61-0.90], p=0.0014). PFS was tested using a hierarchical strategy, such that testing was first performed in patients whose tumors expressed PD-L1 with CPS =10, then in patients whose tumors expressed PD-L1 with CPS =1, with partial alpha from PFS in patients with CPS =10 transferred over, and finally in the ITT population. Thus, statistical significance was not tested in the ITT population (median PFS = 7.5 months for Keytruda plus chemotherapy versus 5.6 months for chemotherapy alone; HR = 0.82 [0.69-0.97]).
Safety was consistent with the known profiles of each regimen, and no new safety signals were observed. Treatment-related adverse events (TRAEs) of any grade occurred in 96.3% of patients receiving KEYTRUDA plus chemotherapy (n=562) and 95.0% of patients receiving chemotherapy (n=281). Grade 3-5 TRAEs occurred in 68.1% of patients receiving Keytruda plus chemotherapy and 66.9% of patients receiving chemotherapy. The most common Grade 3-5 TRAEs (occurring in =10% of patients) were neutropenia (29.7%), decreased neutrophil count (17.4%) and anemia (16.4%) for Keytruda plus chemotherapy and neutropenia (29.9%), decreased neutrophil count (20.3%), and anemia (14.6%) for chemotherapy. TRAEs resulting in discontinuation of any treatment occurred in 18.1% of patients receiving Keytruda plus chemotherapy and 11.0% of patients receiving chemotherapy. There were two treatment-related deaths in patients receiving Keytruda plus chemotherapy.
Immune-mediated adverse events (AEs) of any grade occurred in 25.6% of patients receiving the Keytruda plus chemotherapy and 6.0% of patients receiving chemotherapy. For patients receiving Keytruda plus chemotherapy, the most common immune-mediated AE (occurring in =10% of patients) was hypothyroidism (15.5%). There were no immune-mediated AEs occurring in =10% of patients receiving chemotherapy.
Source:http://www.pharmabiz.com/NewsDetails.aspx?aid=124144&sid=2
“The progression-free survival results observed in KEYNOTE-355 have the potential to impart real change for certain patients with metastatic triple-negative breast cancer in the first-line setting,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Merck is committed to evaluating innovative treatment approaches, anchored by Keytruda, across multiple settings and stages of breast cancer. We are encouraged by the positive results from the phase 3 KEYNOTE-355 and neoadjuvant/adjuvant KEYNOTE-522 studies, which demonstrate the potential of Keytruda in combination with chemotherapy for the treatment of triple-negative breast cancer.”
“There is a significant need for treatment regimens that can help women with metastatic triple-negative breast cancer, an aggressive disease,” said Dr. Javier Cortes, Head Breast Cancer program, IOB Institute of Oncology, Quironsalud Group. “The results of this study, demonstrate that if approved, Keytruda in combination with chemotherapy may offer certain women a new option for first-line treatment.”
These results are being presented as an oral abstract session of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline.
The Keytruda breast cancer clinical development program encompasses several internal and external collaborative studies. In addition to KEYNOTE-355, in TNBC these include the ongoing registration-enabling studies KEYNOTE-242 and KEYNOTE-522.
KEYNOTE-355 is a randomized, double-blinded, phase 3 trial evaluating Keytruda in combination with one of three different chemotherapies compared with placebo plus one of the three chemotherapy regimens for the treatment of locally recurrent inoperable or mTNBC that has not been previously treated with chemotherapy in the metastatic setting. The dual primary endpoints are PFS and OS in patients whose tumors expressed PD-L1 (CPS =1 and CPS =10) and in all participants (intention-to-treat [ITT] population). The secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and safety.
KEYNOTE-355 enrolled 847 patients who were randomized 2:1 to receive Keytruda (200 mg every 3 weeks) plus chemotherapy (investigator’s choice of nab-paclitaxel, paclitaxel or gemcitabine/carboplatin); or placebo plus nab-paclitaxel, paclitaxel or gemcitabine/carboplatin. Among enrolled patients in each treatment group, approximately 75% had tumors expressing PD-L1 with CPS =1 (n = 425/566 for Keytruda plus chemotherapy; n = 211/281 for chemotherapy alone) and approximately 38% had had tumors expressing PD-L1 with CPS =10 (n = 220/566 for KEYTRUDA plus chemotherapy; n = 103/281 for chemotherapy alone).
As of data cut-off for this interim analysis (December 11, 2019), median time from randomization to data cut-off was 25.9 months for Keytruda plus chemotherapy and 26.3 months for chemotherapy alone. Keytruda plus chemotherapy significantly improved PFS versus chemotherapy alone in patients whose tumors expressed PD-L1 with CPS =10 (HR = 0.65 [95% CI, 0.49-0.86], p=0.0012). In patients whose tumors expressed PD-L1 with CPS =1, statistical significance for Keytruda plus chemotherapy was not met, but Keytruda plus chemotherapy improved PFS in this patient population versus chemotherapy alone (median PFS = 7.6 months versus 5.6 months; HR = 0.74 [95% CI, 0.61-0.90], p=0.0014). PFS was tested using a hierarchical strategy, such that testing was first performed in patients whose tumors expressed PD-L1 with CPS =10, then in patients whose tumors expressed PD-L1 with CPS =1, with partial alpha from PFS in patients with CPS =10 transferred over, and finally in the ITT population. Thus, statistical significance was not tested in the ITT population (median PFS = 7.5 months for Keytruda plus chemotherapy versus 5.6 months for chemotherapy alone; HR = 0.82 [0.69-0.97]).
Safety was consistent with the known profiles of each regimen, and no new safety signals were observed. Treatment-related adverse events (TRAEs) of any grade occurred in 96.3% of patients receiving KEYTRUDA plus chemotherapy (n=562) and 95.0% of patients receiving chemotherapy (n=281). Grade 3-5 TRAEs occurred in 68.1% of patients receiving Keytruda plus chemotherapy and 66.9% of patients receiving chemotherapy. The most common Grade 3-5 TRAEs (occurring in =10% of patients) were neutropenia (29.7%), decreased neutrophil count (17.4%) and anemia (16.4%) for Keytruda plus chemotherapy and neutropenia (29.9%), decreased neutrophil count (20.3%), and anemia (14.6%) for chemotherapy. TRAEs resulting in discontinuation of any treatment occurred in 18.1% of patients receiving Keytruda plus chemotherapy and 11.0% of patients receiving chemotherapy. There were two treatment-related deaths in patients receiving Keytruda plus chemotherapy.
Immune-mediated adverse events (AEs) of any grade occurred in 25.6% of patients receiving the Keytruda plus chemotherapy and 6.0% of patients receiving chemotherapy. For patients receiving Keytruda plus chemotherapy, the most common immune-mediated AE (occurring in =10% of patients) was hypothyroidism (15.5%). There were no immune-mediated AEs occurring in =10% of patients receiving chemotherapy.
Source:http://www.pharmabiz.com/NewsDetails.aspx?aid=124144&sid=2
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