FDA Approves Rasonque™ (daraxonrasib)

The U.S. Food and Drug Administration has granted approval for a new drug targeting the mutations that drive more than 90% of pancreatic cancer cases - a sweeping advance for a disease that has few treatment options and a five-year survival rate of just 13%.

Rasonque™ (daraxonrasib) is approved for the treatment of adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. This is now considered the new standard of care for patients with previously treated metastatic pancreatic cancer after clinical trial results in this population showed a doubling of survival compared to chemotherapy as well as improved quality of life for patients.

It's a moment that marks the beginning of a new era of treatment for pancreatic cancer, said PanCAN Chief Scientific and Medical Officer Anna Berkenblit, MD, MMSc.

"The FDA approval of Rasonque is the most significant advancement we have ever seen in the fight against pancreatic cancer," said Dr. Berkenblit. "This drug will transform how we treat pancreatic cancer - giving people the opportunity for more time with loved ones, the possibility of a better quality of life and renewed confidence that continued research will deliver even greater advances."

Here, PanCAN answers questions related to this new treatment option.

What is Rasonque (daraxonrasib)?

Rasonque is a targeted therapy called a RAS inhibitor. It has been granted approval by the FDA for the treatment of adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. This means the treatment may be an option for people with pancreatic cancer who have or have not had prior therapy. It is a once-daily pill.

What does this FDA approval mean?

With FDA approval, Rasonque is now available for the treatment of adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. Now oncologists can prescribe this once-daily pill for the patient population it was approved for. Previously, it was only available through clinical trials and more recently an Expanded Access Program. Patients receiving Rasonque through the Expanded Access Program will be transitioned to commercial supply through their insurance.

What is the survival benefit for patients with pancreatic cancer?

Phase III clinical trial results from the clinical oncology company Revolution Medicines showed that Rasonque doubled overall survival as compared to standard chemotherapy in patients with previously treated metastatic pancreatic cancer. Rasonque demonstrated a median overall survival of 13.2 months versus 6.7 months for chemotherapy. Overall survival measures the length of time from when treatment begins until death from any cause.

Clinical trial participants who received Rasonque also had a better quality of life and improved pain control as compared to patients treated with chemotherapy.

Phase III clinical trial results from Revolution Medicines were announced in April, with additional data released in the New England Journal of Medicine and the American Society of Clinical Oncology meeting in May.

What are RAS mutations and why have they been a focus for researchers studying treatments for pancreatic cancer?

RAS mutations are changes in the RAS family of genes, which regulate cell growth and division. Mutations in RAS can cause cancer cells to grow uncontrollably, leading to cancer. They can essentially "switch on" signals for constant cell growth, driving tumor formation and progression. These mutations are typically somatic mutations, meaning they occur in cells during a person's lifetime and are not inherited. RAS mutations, particularly in the KRAS gene, are found in over 90% of pancreatic cancer cases. RAS inhibitors like Rasonque work by stopping the activity of RAS proteins, blocking signaling pathways that promote growth. Identifying a KRAS mutation can guide treatment strategies and eligibility for clinical trials.

For decades, RAS mutations were considered "undruggable." Now, that tide has turned. This represents the first FDA approval of a RAS-targeting therapy that is broadly effective for this disease, greatly expanding the potential benefit of targeted therapies for patients with pancreatic cancer.

I am a patient interested in Rasonque. What should I do?

People diagnosed with pancreatic cancer should talk to their healthcare team about this treatment option. And contact PanCAN Patient Services for one-to-one support. Our Case Managers are ready to help you prepare for an informed conversation with your doctor about treatment options. Every patient is unique, and treating pancreatic cancer will look different at every stage. We can point you in the right direction for more information and answer questions as you explore options.

Although Rasonque was approved regardless of RAS mutation status, PanCAN continues to recommend biomarker testing for all patients with pancreatic cancer. This testing looks for mutations and other changes specific to each patient's tumor. Patients who do not have a KRAS mutation are more likely to have a different actionable alteration and may benefit from other treatments. Also, biomarker testing results can help identify subsequent therapies when the current therapy is no longer working. Lastly, biomarker testing may help open the door to ongoing clinical trials.

If you've already had biomarker or genetic testing, PanCAN Patient Services can help you understand your results and give you information about treatment options, including clinical trials .

What are the side effects of Rasonque?

The most common side effects reported by patients in the RASolute-302 clinical trial include rash, stomatitis (mouth sores) and diarrhea. Roughly 86% of patients reported rash, with about 14% of those cases considered severe. Stomatitis - commonly known as mouth sores - was the second-most severe side effect: It was reported by 54% of participants, with 12% of cases severe. Side effects may be managed with dose interruptions and/or dose reductions of Rasonque. Side effects led to stopping Rasonque permanently in 1.2% of patients in the clinical trial.

Supportive care and proactive management of these side effects will be key for patients receiving Rasonque. For rash, treatment options include sun protection with sunscreen, oral tetracycline antibiotics and topical corticosteroids. For mouth sores, an oral hygiene routine that includes regular brushing/flossing, alcohol-free mouth rinses and diet modifications to avoid irritation may help. Revolution Medicines plans to offer comprehensive patient support through their (ON)Path™ program.

Remember, it is important to talk to your doctor about any side effects you experience. Your doctor will be able to help address any issues early on, to help maintain and improve quality of life.

Download PanCAN's comprehensive booklet, Supportive Care: Quality of Life and Practical Care in Pancreatic Cancer, for more information about how to manage symptoms and side effects.

Does insurance cover this treatment?

FDA approval means this drug is safe and effective, and although the FDA does not decide what is covered by insurance, when a drug gets FDA approval Medicare and Medicaid will usually cover it.  Coverage will vary based on the specific plan and insurance company a person uses. Revolution Medicines' (ON)Path™ program may also be a resource.

Contact PanCAN Patient Services for more information on financial, insurance and other support resources available for those experiencing or anticipating cost-related barriers to care.

What's next for this treatment? Are there other potential treatment options like Rasonque on the horizon?

While the approval of Rasonque represents a step forward, we know that not every patient's tumor will respond and that some tumors can initially respond and then develop resistance to targeted therapies over time. Ongoing clinical trials are testing whether Rasonque in combination with chemotherapy or other targeted therapies provides additional benefit. Rasonique is also being tested by itself after surgery to see if it prevents pancreatic cancer from coming back again. There are also many other therapies in clinical trials targeting KRAS and other mutations.

PanCAN encourages patients diagnosed with pancreatic cancer to consider clinical trials at every treatment decision. Contact PanCAN Patient Services to be connected to a Case Manager who can conduct a personalized clinical trial search.