Is the K drug with 30 indications expected to conquer pancreatic cancer?

Article source: Med

Author: MedWatch × Xixi

Adenocarcinoma (pancreatic ductal adenocarcinoma) is a highly malignant malignant tumor of the digestive system that is difficult to diagnose and treat.

Worthy of this title, the success rate of clinical trials for patients with pancreatic cancer is "reversed" among all solid tumors, and the failure rate of phase 3 clinical trials is as high as 72%

Clinical research success rate of different solid tumors (Source: NextPharma database)

Therefore, it is not difficult to understand that surgery, radiotherapy, and chemotherapy are still the main treatments for pancreatic cancer

Although immunotherapy has achieved exciting results in various tumors such as melanoma, bladder cancer, breast cancer, NSCLC and kidney cancer; however, in the field of pancreatic cancer, studies so far have not confirmed that PD-1 alone can effectively prolong The survival time of patients with pancreatic cancer, in the latest phase I and II studies, also affected the credibility of the conclusions due to insufficient sample size

Immune single medicine is not enough, come with combined treatment!

In the past two years, many small-sample clinical studies have shown preliminary treatment prospects

List of PD-1 combination therapies in the field of pancreatic cancer

According to the NextPharma database, we sorted out the published clinical results of PD-1 combination therapy in the field of pancreatic cancer

Not long ago, the K drug, which was awarded the 30th indication in the FDA, is ambitious, and it is combined with chemotherapy, radiotherapy, targeted therapy (trametinib, acatinib), cancer vaccine (GVAX), CXCR4 antagonist (motixafortide), Anti-SDF-1 aptamer (olaptesed pegol) and oncolytic virus (pelareorep) have been jointly explored

Drug O has adopted a completely different strategy.

Domestically, Hengrui, Junshi, and WuXi Biologics have chosen the indications for the first-line treatment of advanced pancreatic ductal carcinoma for PD-1 by coincidence, and the combined plan is not bad

Is K drug expected to conquer pancreatic cancer?

Closer to home, a few days ago, Drug K published two phase 2 clinical studies on the combined treatment of pancreatic cancer in the top journals "Lancet oncol" (Lancet oncol) and "Clinical Cancer Research" (CCR), which are worthy of everyone's attention.

Local recurrence after pancreatic cancer surgery, or welcome choice?

The 5-year survival rate of pancreatic cancer is less than 8%.

In August, Lancet Oncol reported an open-label, randomized, controlled phase II trial to evaluate stereotactic radiotherapy (SBRT) combined with pembrolizumab and trametinib vs SBRT combined with gemcitabine in locally advanced pancreatic cancer The curative effect

The enrolled patients were histologically diagnosed as pancreatic ductal adenocarcinoma, characterized by positive immunohistochemical staining of mutant KRAS and PD-L1, ECOG PS 0-1, and local recurrence after postoperative chemotherapy

Randomly assigned (1:1) to receiving SBRT, intravenous pembrolizumab 200 mg once every 3 weeks, oral trametinib 2 mg once daily; or receiving on days 1 and 8 of a 21-day cycle SBRT and intravenous gemcitabine continued for 8 cycles until disease progression, death, unacceptable toxicity or withdrawal of informed consent

The results of the study showed that the combined treatment model can significantly prolong the patient's OS (24.

Pancreatic ductal adenocarcinoma, triple therapy is safe and well tolerated

Pancreatic ductal adenocarcinoma (PDAC) is basically unresponsive to immune checkpoint inhibitors.

Recently, Clin Cancer Res published a multi-center, single-arm Phase II study (COMBAT/KEYNOTE-202 trial), which aims to evaluate the CXCR4 antagonist motixafortide + PD-1 inhibitor pembrolizumab + chemotherapy The efficacy of triple therapy for PDAC
.

A total of 43 patients with new metastatic PDAC who had disease progression after first-line gemcitabine treatment were included in the study
.
Patients receive daily motixafortide pre-excitation treatment on days 1-5, followed by motixafortide twice a week, pembrolizumab once every 3 weeks, and nanoliposome irinotecan, fluorouracil and leucovorin once every 2 weeks (NAPOLI-1 program)
.
The primary endpoint is ORR, and secondary endpoints include OS, PFS, disease control rate, safety and tolerability
.

COMBAT/KEYNOTE-202 trial key efficacy results (source: CCR)

The results showed that the ORR of the overall population was 21.
1%, and the confirmed ORR was 13.
2%; DCR reached 63.
2%, the median duration of remission was 5.
7 months, mPFS was 3.
8 months, and mOS was 6.
6 months
.
The triple therapy is safe and well tolerated, and its toxicity is comparable to that of the NAPOLI-1 regimen
.
It is worth noting that the incidence of grade 3 or above neutropenia and infection is 7%, which is lower than expected by this chemotherapy regimen
.

All in all, the above two studies have initially demonstrated the potential application prospects of K-drug combination therapy, and a large number of prospective studies are needed for further verification in the future
.