FDA has approved a supplemental Biologics License Application updating the Opdivo (nivolumab) dosing schedule to include 480 mg infused every four weeks for a majority of approved indications.
Opdivo can now be infused over 30-minutes across all approved indications, instead of over an hour, said Awny Farajallah, vice president and head of U.S. Medical Oncology at Bristol-Myers Squibb.
“I think the significance is this should give patients and providers an option,” Farajallah said. “If they want to monitor the patient more closely, then they go with the two-week therapy, and if their patient is stable, then they go with four weeks.”
The four-week dosing option is approved for the following indications:
Metastatic melanoma (monotherapy or monotherapy phase after combination treatment with Yervoy [ipilimumab]),
Previously treated metastatic non-small cell lung cancer,
Advanced renal cell carcinoma following prior anti-angiogenic therapy,
Previously treated locally advanced or metastatic urothelial carcinoma following disease progression during or after platinum-based chemotherapy,
Classical Hodgkin lymphoma following relapse/progression after autologous hematopoietic stem cell transplantation and brentuximab vedotin, or three or more lines of systemic therapy that includes autologous HSCT,
Recurrent/metastatic squamous cell carcinoma of the head and neck following platinum-based therapy,
Hepatocellular carcinoma after prior sorafenib therapy, and
Adjuvant therapy for patients with completely resected melanoma with lymph node involvement or metastatic disease.
PD-1/PD-L1-based therapies have become the standard of care, especially in the non-small cell lung cancer setting, where almost 40 percent of patients are treated with these drugs across all lines (The Cancer Letter, June 2, 2017).
Farajallah spoke with Matthew Ong, a reporter with The Cancer Letter.
Matthew Ong: How is the new four-week dosing option different from how Opdivo was used previously?
Awny Farajallah: Our previous indications or previous dosing was actually every two weeks, so we did not have the flexibility of Q4W that we recently received the last couple of days.
We went from every two weeks to every four weeks, but with the understanding that it’s not a switch—we still can provide the drug every two weeks or every four weeks if you so choose. Basically, it is dependent on the patient situation. The provider and the patient would decide and allow flexibility between the two doses.
If the patient has a recent diagnosis and he or she needs closer follow-up, then two-week dosing may be appropriate if the physician chooses to do so. If the patient has been stable and clinically doing well, then maybe a four-week dosing would be the choice of the physician at the time. That flexibility for the patient depending on the clinical status is really going to be a provider decision.
Currently, Opdivo is the only immuno-oncology agent that is approved for a four-week infusion, which is different from other IO agents that are currently available to patients.
I think the significance is this should give patients and providers an option. If they want to monitor the patient more closely, then they go with the two-week therapy, and if their patient is stable, then they go with four weeks.
Additionally, the update included a 30-minute infusion rather than a 60-minute infusion, so the original dosing was to infuse Opdivo over 60 minutes. But now, it allows for a shorter time of preparation, shorter time for the patient in the clinic in the infusion chair, which is significant for the patient, of course.
A good number of pharmaceutical companies with cancer portfolios are stepping up their work on real-world evidence and patient-reported outcomes. What are BMS’s efforts on that front?
AF: We definitely heavily invest in real-world evidence generation at multiple levels, not just at the patient-reported outcomes, which are incorporated in every clinical trial that we have. But also understanding how our drugs are behaving in the real world, especially in populations that we have not studied in the clinical trials, and try to generate data on this.
We have heavy investment from the research standpoint as well as, again, looking at when to partner externally when we don’t have the right datasets, etc. to be able to answer the clinical questions that we’re looking to answer.
What else is coming along in BMS’s oncology pipeline?
AF: There’s a lot going on. We’re really looking at cancer from all angles. The mission of the company is to leave no cancer patient behind.
Our pipeline has 18 clinical-stage assets currently that we’re studying across 50 tumor types—research from early development, translational medicine, and full clinical development. We also have a robust discovery pipeline as well that we’re looking at other mechanisms of action to bring to the clinic.
In addition to that, our focus is really bringing the right treatment to the right patient at the right time, and how do you select those regimens and those drugs for the patients with those robust biomarkers. When we don’t have the assets that we think have a good mechanism of action, we actively engage in clinical collaborations or licensing.
As you probably have seen, we have announced the clinical collaboration recently with Nektar Therapeutics to co-develop and do a clinical development plan for their lead immuno-oncology program, NKTR-214, a CD122-biased agonist. So, this is an example of us looking at an established mechanism of action that’s proven in the clinic to see how to combine it with our current portfolio.
That’s kind of the big picture. Going to your question about regulatory approvals that we may expect, as you know, we have an active ongoing discussion with FDA that we have announced around our potential first-line renal-cell carcinoma combination therapy. We certainly are hopeful that this will move forward.
