Sitting at the crest of the wave of checkpoint inhibitors that changed the game in oncology and made Merck & Co. the pharma behemoth it is today, Keytruda has come a long way in its more than eight years on the market.
The cancer immunotherapy — which works by priming tumors to be eliminated by a patient's immune system — has had a storied history of treating more than a million patients with many different kinds of cancers, Merck vice president of oncology clinical research Dr. Gregory Lubiniecki, said in an interview. It's also the bestselling cancer drug in the world a few years running and is set to become the bestselling drug overall next year.
One of the reasons the drug is so successful is how versatile it is, winning approval after approval for different types of cancers, including some of the trickiest out there. Another is its longevity, as demonstrated most recently by five-year survival studies in patients with non-small cell lung cancer, the company presented at this year's European Society for Medical Oncology (ESMO) annual meeting in September. In the two trials, a regimen of Keytruda with chemotherapy resulted in almost 20% of patients with the deadly disease living for five years.
Here, Lubiniecki talks about Keytruda's successes as it approaches a decade on the market, what the long-term benefit of the drug means for patients and the oncology community, and the future of combinations and newer treatments.
This interview has been edited for style and brevity.
PHARMAVOICE: How would you characterize Keytruda's trajectory over time since its very first approval in 2014 to the place it currently holds in the oncology arena today?
DR. GREGORY LUBINIECKI: Keytruda has had an amazing trajectory. I can say that we've treated over a million patients commercially, and there have been over 40 indications across over 20 different tumor types. And that includes pan-tumor indications covering microsatellite instability and tumor mutation burden-high indications, and these have been transformative in patient care. A number of these have been based off a demonstration of an improved survival benefit for patients, and what we saw at ESMO this year are long-term outcomes for lung cancer, head and neck cancer and melanoma.
These long-term studies are really game-changing. Did you think back at the beginning of the journey that these results would eventually be realized?
This is certainly very surprising and inspiring. When the journey began, it was clear that Keytruda's mechanism of action had a role to play in patients with melanoma, kidney cancer and non-small cell lung cancer — and so being data driven, initially it seemed as though it may have just been very limited, but as we began to explore other opportunities, we found other indications where the monotherapy could have benefit. We found a biomarker that could help with patient selection to identify the patients most likely to benefit, and then we also opened ourselves up to the possibility of combination therapy in an agnostic fashion.
"I suspect that for other combinations going forward Keytruda is going to be the control arm for those trials as it is such an important part of standard-of-care for many tumors."
Dr. Gregory Lubiniecki
Vice president of oncology research, Merck
In some cases, we combined Keytruda with chemotherapy. And you would think, well, some of the chemotherapy perhaps will kill off the immune cells that have been activated around the tumor site, as well as other ways they might not work together. But still, you're having the benefit of two different therapies on board, and in a number of instances, it's been demonstrated that the chemotherapy is not working at odds against the checkpoint inhibitor and the two drugs are able to produce their desired effect in the patients and result in overall benefit for the majority of patients treated.
It's exciting to see all the trickier cancers you're able to target now with drug combinations. How do you approach finding a good combination candidate?
Merck opted to take an agnostic approach to the development of combination work with Keytruda — this philosophy has been led by Dr. Roy Baynes, who's no longer at Merck, and Eric Rubin and Emmett Schmidt. We have been willing to partner with other companies so they can test their products with Keytruda, and when we see that there is greater activity with the combination over what one might expect with a single agent, then we've thought, OK, this looks like it's something worth taking forward.
What are the unique qualities that Merck brings to a partnership, and then qualities that a company like Eisai or AstraZeneca, for example, might contribute to make it successful overall?
The partnerships are a very special aspect of the development program at Merck. And certainly two heads addressing a problem are better than one. So it's good to have the input from people at both companies working on trying to solve this problem of cancer drug development and trying to improve the lives of patients with cancer. Often, each company will agree to provide their drug and it's decided which company can run a protocol. And you have the people from development at both companies contributing to the design of that study and any plans for next steps thereafter. I think it's a benefit for patients and for science to have this joint approach to trying to tackle the problem.
What do you see as the shining light for Keytruda moving forward? Long-term survival, more indications, drug combinations — what drives Keytruda into its next phase?
When it became apparent how broad Keytruda's benefit is for patient care, an effort was made to demonstrate the value through clinical trials. It's at the point now where Keytruda is foundational in the care of many patients early on in a first-line setting and in some cases a second-line or greater setting. And we're looking at a number of studies in earlier stages of disease, both locally advanced and resectable, so it's expected that the ability of Keytruda to play a role in the care of patients at any stage of their disease is being explored. There are a little over 80 opportunities left for studies yet to be read out to demonstrate this benefit, and I suspect that for other combinations going forward Keytruda is going to be the control arm for those trials as it is such an important part of standard-of-care for many tumors.
What are you excited about in the field of oncology? Are there trends you see as most promising to the landscape going forward?
I'm very excited to see more of these trials in the earliest stages of cancer with checkpoint inhibitors like Keytruda reading out, because there's an opportunity to make yet another impact on the lives of patients with cancer. We've seen in a few of the studies that have read out so far that there is a progression- or relapse-free survival benefit in some of these studies — but I'm very interested and excited to see if we can identify a benefit in overall survival, which can be very challenging. Even in the era when chemotherapy was the predominant therapeutic option, it took a long time for these adjuvant studies to demonstrate survival benefit. Now with the advent of immunotherapy as a next line of therapy for when patients relapse, it may take even longer for us to see the benefit of immunotherapy in an adjuvant setting to show us an overall survival benefit.
And we're on the cusp of seeing more data from antibody-drug conjugates, and it will be interesting to see how these change the landscape in cancer care, as we're now able to try and deliver chemotherapy in a more targeted setting, right to the tumor cells, ideally speaking.