Scot Ebbinghaus, Vice President and Therapeutic Area Head, Oncology Clinical Research, Merck Research Laboratories, took time out ahead of the meeting to discuss three of the company’s clinical trials being presented and the implications for oncology patients and Merck.
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Over the weekend, Merck & Co. presented plenty of abstracts at the American Society of Clinical Oncology (ASCO) Annual Meeting—to say the least. In fact, Merck presented 140 abstracts on 25 different cancer types at the meeting.
Scot Ebbinghaus, Vice President and Therapeutic Area Head, Oncology Clinical Research, Merck Research Laboratories, took time out ahead of the meeting to discuss three of the company’s clinical trials being presented and the implications for oncology patients and Merck.
The three trials, specifically, are KEYNOTE-001, KEYNOTE-062 and POLO.
Ebbinghaus notes, “I’ve been working on the Keytruda program almost since there was one. I joined in 2012, and then we had about 50 or so melanoma patients on Keytruda, which looked really interesting. It was first used in humans in 2011. And over the past eight years, since the first time Keytruda was given to a human, we have had tremendous growth in the program, which really underscores how transformational the anti-PDL1 drugs in general and Keytruda specifically have been for the treatment of cancer.”
The KEYNOTE-001 trial data Merck presented was in in non-small cell lung cancer (NSCLC). Ebbinghaus says, “It’s a good starting place because it is fundamental to our overall strategy for Keytruda and Merck Oncology. KEYNOTE-001 established Keytruda as a monotherapy as a foundation for treatment for cancer. And it was actually the name of the first study we ever did with Keytruda, starting in 2011 when it enrolled its first patient.”
It expanded to over 1,000 patients who were about 50/50 for melanoma and lung cancer. “This is our longest experience with Keytruda in any disease and the data we’re presenting at ASCO is the 5-year survival data for lung cancer.”
Lung cancer is the most common cause of cancer death in the U.S. and around the world. In the pre-immunotherapy era, in the previous decade, the 5-year survival rate for lung cancer was about 5%. “Now,” Ebbinghaus says, “in Keynote-001, depending on which specific group of patients you’re looking at, whether as a first-line setting or in patients with high PDL1 expression, you’re looking at overall survival in the 15 to 25% range. That still leaves a lot of room for growth and improvement through combinations, but if you put it into context of what it was then, that’s really a profound movement.”
KEYNOTE-062 is a Phase III trial of Keytruda as a monotherapy and in combination with chemotherapy (cisplatin and either 5-flurouracil or capecitabine) for the first-line treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Gastric cancer is about the fifth most common cause of cancer deaths around the world with a high disease burden.
Ebbinghaus told BioSpace, “The way the trial is designed, we evaluated Keytruda compared to chemotherapy for what’s called non-inferiority, which means in lay terms, as good or better than chemotherapy as first-line treatment for stomach cancer and in patients with low-level PDL1 expression, and that’s what it showed. In patients with higher levels of PDL1 expression, the overall survival data looked even better.”
He went on to say, “Why that’s important is that two-drug chemotherapy for stomach cancer can be pretty toxic. Some patients aren’t necessarily great candidates for chemotherapy, so if this were to be approved by the FDA and other agencies around the world, it could represent another option for patients with gastric cancer that’s at least as good as chemotherapy but with a less toxic profile.”
And the third trial discussed was POLO. POLO is a Phase III clinical trial being conducted with AstraZeneca in pancreatic cancer. The trial investigated Lynparza, the world’s first PARP inhibitor, co-developed and co-commercialized by the two companies.
Ebbinghaus said, “I think this is a great progression, from the pillars of our strategic program, establishing a foundation of a monotherapy, building on it with combinations, and lastly, building on our success with Keytruda by forming these strategic alliances with other companies like AstraZeneca and Eisai.”
Metastatic pancreatic cancer is a very difficult disease to treat and progress in the area has been extremely limited, even for immunotherapeutics. In this trial, the companies showed that patients with pancreatic cancer and BRCA1 and BRCA2 mutations had a very strong progression free survival (PFS) benefit when treated with the drug following chemotherapy. “What we showed,” Ebbinghaus said, “was about a 50% improvement in the PFS endpoint of these patients and that translated into about 20 to 22% of patients were alive and progression-free at two years following randomization compared to patients who received chemotherapy alone.”
The bottom line of these three trials, out of the 140 abstracts the company presented, is, Ebbinghaus said, “they show in order the potential for patients to have long-term benefit from immunotherapies in diseases like lung cancer. I think they show that in the context of the broader Keytruda program, Keytruda has demonstrated survival benefit across multiple tumors, and over five years that important role of Keytruda continues to grow and expand the number of types of tumors it can be used to treat.”
Ebbinghaus outlines the two different pathways Merck expects to build on what they have to date. The first, he says, is to further evaluate and improve on the foundation they’ve laid with Keytruda in the company’s combination program. “We have a very large program to evaluate combinations and signal-finding and have collaborated with a number of industry partners to do signal-finding in a variety of combinations and a variety of diseases. A number of those are starting to show interesting results and we’re moving into registration development.”
The second pathway is to evaluate Keytruda in earlier stages of disease. As Ebbinghaus points out, the trials discussed so far have been in cancer that has metastasized. “What we would like to do,” he says, “is use Keytruda in an earlier setting, for example after cancer surgery, to reduce the risk of cancer coming back.”
To date they’ve had one study in melanoma, KEYNOTE-54, read out. It evaluated Keytruda in Stage 3 melanoma post-operatively and showed a clinical relapse-free survival benefit that led to its approval in the U.S., Europe, Japan and other countries. Ebbinghaus says, “We’ve expanded on that concept and have a large portfolio of studies in the adjuvant, neoadjuvant or locally advanced disease setting, and a few of those trials-in-progress will be presented at ASCO. So that’s a second important direction with our Keytruda program.”
