Merck's Keytruda Demonstrates Positive Results Across Four Phase 3 Cancer Trials

▎WuXi

Edited by Kant Content Team

Today, MSD announced its重磅PD-1 inhibitor at the European Society for Medical Oncology (ESMO) conference.Positive Results from Multiple Phase 3 Trials of Keytruda in Cervical Cancer, Breast Cancer, Non-Small Cell Lung Cancer (NSCLC), and Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma。

Keytruda is a humanized anti-PD-1 monoclonal antibody that blocks the binding of PD-1 to its ligands PD-L1 and PD-L2, thereby activating T lymphocytes. This action may enhance the ability of the immune system to detect and combat tumor cells.In September 2014, Keytruda was first approved by the FDA for the treatment of advanced melanoma and was subsequently approved as a first-line therapy for patients with metastatic NSCLC. In China, Keytruda has also been approved for multiple indications, covering melanoma, NSCLC, head and neck squamous cell carcinoma, colorectal cancer, esophageal cancer, liver cancer, and more.

The trial results announced this time are as follows:

Significantly Improve the Risk of Disease Progression or Death in Patients with Locally Advanced Cervical Cancer

KEYNOTE-A18 Trial: Evaluating the Efficacy and Safety of Keytruda in Combination with External Beam Radiation Therapy (EBRT) and Concurrent Chemotherapy, Followed by Brachytherapy (Also Known as Concurrent Chemoradiotherapy), in Newly Diagnosed High-Risk Locally Advanced Cervical Cancer Patients (Stage IB2-IIB with Positive Lymph Nodes, Stage III-IVA).

The trial results showed that, after a median follow-up of 17.9 months (range: 0.9-31.0), compared with patients who received only concurrent chemoradiotherapy, those who receivedThe combination therapy regimen of Keytruda with concurrent chemoradiotherapy reduced the risk of disease progression or death by 30% (HR=0.70, 95% CI: 0.55-0.89, p=0.0020).The median progression-free survival (PFS) has not yet been reached in either group. The 24-month progression-free survival rate was 67.8% for patients receiving Keytruda in combination therapy, compared to 57.3% for those receiving concurrent chemoradiotherapy alone. In addition to the improvement in progression-free survival, the Keytruda regimen also showed a favorable trend in overall survival (OS), another primary endpoint of the trial, compared to the control group (HR=0.73, 95% CI: 0.49-1.07).

According to the press release,KEYNOTE-A18 is the first Phase 3 trial to show that an immunotherapy regimen significantly improves progression-free survival in patients with locally advanced cervical cancer compared to those receiving concurrent chemoradiotherapy alone.

Significantly Improve Pathological Complete Response (pCR) in Breast Cancer Patients

MSD Announces First Results from the Neoadjuvant Portion of KEYNOTE-756 Trial, Evaluating Keytruda in Combination with Chemotherapy as Neoadjuvant Therapy Followed by Keytruda Plus Endocrine Therapy as Adjuvant Therapy for High-Risk, Early-Stage, Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer Patients.

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Analysis Shows That Preoperative Keytruda Combined with Chemotherapy Achieves One of the Dual Primary Endpoints—Pathological Complete Response. Compared with Placebo + Chemotherapy, the pCR Rate of Keytruda Combination Therapy Showed Statistically Significant Improvement.The pathological complete response rate was 24.3% in patients (n=154/635) receiving Keytruda combination therapy as neoadjuvant treatment, compared to 15.6% in the placebo group (n=100/643), with an estimated increase of approximately 8.5% (p=0.00005).

According to the press release,KEYNOTE-756 is the first Phase 3 trial to show that immunotherapy significantly improves the pathological complete response rate in this patient population.

Significantly Improve Overall Survival in Patients with Resectable NSCLC

KEYNOTE-671 trial evaluates Keytruda as a perioperative therapy (including neoadjuvant therapy before surgery and adjuvant therapy after surgery) for the efficacy and safety in treating patients with resectable stage II, IIIA, or IIIB NSCLC.

The second pre-planned interim analysis of the trial showed a median follow-up time of 36.6 months (range: 18.8-62.0 months). Compared with patients who received placebo + chemotherapy as neoadjuvant therapy and placebo as adjuvant therapy,Patients receiving Keytruda + chemotherapy as neoadjuvant therapy and Keytruda monotherapy as adjuvant therapy showed a significant improvement in overall survival (one of the dual primary endpoints), with a 28% reduction in the risk of death (HR=0.72, 95% CI: 0.56-0.93, one-sided p=0.00517). This result was independent of PD-L1 expression in patient tumors.Patients receiving the Keytruda regimen have not yet reached the median overall survival (95% CI: not estimable–not estimable), while the median overall survival for patients on the chemotherapy-placebo regimen was 52.4 months (95% CI, 45.7–not estimable). The 36-month overall survival rate was 71.3% for patients in the Keytruda group and 64.0% for those in the control group. Additionally,Keytruda Group Shows Statistically Significant Improvement in Another Primary Endpoint, Event-Free Survival (EFS), with Median EFS Increased by Nearly 2.5 Years: 47.2 Months for Keytruda Group vs. 18.3 Months for Control Group.

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According to the press release,This Keytruda regimen is the first targeted PD-1/L1 therapy to demonstrate a statistically significant improvement in overall survival compared to placebo plus chemotherapy as neoadjuvant therapy and placebo as adjuvant therapy in patients with resectable NSCLC, regardless of PD-L1 expression in the patient's tumor.

Significantly Improve Progression-Free Survival in HER2+ Gastric or GEJ Adenocarcinoma Patients

KEYNOTE-811 trial evaluates the efficacy and safety of Keytruda in combination with trastuzumab, fluorouracil, and platinum-containing chemotherapy as a first-line treatment for patients with HER2-positive locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.

After a median follow-up of 28.4 months, the Keytruda combination therapy demonstrated a statistically significant improvement in PFS in the HER2-positive advanced intent-to-treat (ITT) patient population.Compared with patients treated with trastuzumab and chemotherapy alone, the risk of disease progression or death was reduced by 28% (HR=0.72, 95% CI: 0.60-0.87, p=0.0002).In patients with tumors expressing PD-L1 (Combined Positive Score [CPS] ≥1), the Keytruda regimen also demonstrated clinically meaningful improvement in PFS. Compared to the active control group, the risk of disease progression or death was reduced by 30% (HR=0.70, 95% CI: 0.58-0.85). Based on a pre-specified subgroup analysis, the PFS improvement observed in the ITT population was limited to patients with tumors expressing PD-L1. In the study, more than 80% of patients had tumors expressing PD-L1.