AstraZeneca's Imjudo finally snags first approval—only in an ever-crowded liver cancer field

AstraZeneca’s long-troubled cancer immunotherapy tremelimumab has finally secured its first FDA approval, but the regulatory blessing comes in what could be an increasingly competitive tumor type.

To be sold under the brand name Imjudo, tremelimumab has won an FDA go-ahead in combination with AstraZeneca’s PD-L1 inhibitor Imfinzi for treating unresectable hepatocellular carcinoma, the most common type of liver cancer.

The FDA nod officially puts an end to the streak of clinical trial failures that tremelimumab endured over recent years in multiple cancer types, including non-small cell lung cancer, head and neck cancer and bladder cancer. But while the CTLA-4 inhibitor has now crossed the regulatory finish line, a commercial fight lies ahead.

Thanks to an FDA approval in 2020, Roche’s combination of PD-L1 blocker Tecentriq and anti-VEGF agent Avastin has become a standard of care in newly diagnosed liver cancer. That approval was based on phase 3 data showing the combo could slash the risk of death by 42% over Bayer’s Nexavar.

In its own Himalaya trial, the Imfinzi-Imjudo pair only cut the risk of death by 22% against Nexavar. At three years, an estimated 30.7% of patients in the combo group were still alive, a rate that AZ labeled “unprecedented.”

The three-year survival rate is “quite compelling relative to the other competitive datasets within the space,” AstraZeneca’s oncology business chief David Fredrickson said in an interview with Fierce Pharma. For its part, Roche hasn’t reported three-year survival for the Tecentriq-Avastin combo.

Fredrickson also touted Imfinzi-Imjudo’s safety profile. Specifically, investigators saw no increase in severe liver toxicity or bleeding risk, which are important factors when considering treatment for liver cancer patients, the AZ exec said.

After Imjudo’s multiple prior flops alongside Imfinzi, AZ developed a new regimen for the PD-L1/CTLA-4 combo called STRIDE in liver cancer. It involves a priming dose of Imjudo added to Imfinzi, followed by Imfinzi alone every four weeks.

Still, despite Tecentriq-Avastin’s seemingly better efficacy data, the STRIDE regimen now becomes the first FDA-approved dual immunotherapy treatment regimen in liver cancer.

Fredrickson acknowledged that the low-hanging fruit right now for Imfinzi-Imjudo are patients who aren’t eligible to receive an anti-VEGF agent, and the combo’s early uptake will come from those patients. But AZ’s marketing focus is on all patients based on the Himalaya data, he said.

As AstraZeneca gears up to launch, the company doesn’t have to worry about the two main PD-1 powerhouses—Merck & Co.’s Keytruda and Bristol Myers Squibb’s Opdivo—at least for now.

BMS previously withdrew a later-line Opdivo liver cancer nod after a confirmatory trial miss in the first-line setting. And Merck and Eisai’s Keytruda-Lenvima just posted a surprise failure in frontline liver cancer, although an exceptionally strong performance from that trial’s Lenvima arm could be viewed as support for using that tyrosine kinase inhibitor alone.

Still, more PD-1/L1 rivals are lining up in the liver cancer lane. In a potential direct threat to AZ’s Imfinzi-Imjudo regimen, BMS is conducting the phase 3 CheckMate-9DW trial pitting the PD-1/CTLA-4 combo of Opdivo and Yervoy against either Nexavar or Lenvima. However, that trial now poses some risks given Lenvima’s outstanding performance in that earlier Keytruda trial by Merck.

In addition, Jiangsu Hengrui Pharma and Elevar Therapeutics’ PD-1/VEGFR combo of camrelizumab and rivoceranib (apatinib)—both approved in China—also topped Nexavar in a global phase 3 trial in newly diagnosed liver cancer. But that study’s heavy Asian representation has raised concerns about its implications for the U.S. patient population.

Yet in a positive note, Elevar said two weeks ago that it had a good meeting with the FDA, confirming its plan to file the camrelizumab-rivoceranib combo in 2023. The company cited efficacy results that are “generally consistent across all subgroups.”

Beyond those companies, Novartis and BeiGene recently showed their PD-1 inhibitor tislelizumab alone could match up to Nexavar at extending the lives of patients with newly diagnosed liver cancer. That phase 3 trial is “intended to support global registrations,” a BeiGene spokesperson previously told Fierce Pharma, although the partners haven’t detailed a regulatory plan for that indication.

AZ also has an Imfinzi monotherapy application under review at regulators outside the U.S. in frontline liver cancer. It’s also based on the Himalaya trial showing Imfinzi achieved similar efficacy as Nexavar but with fewer side effects.

AZ’s focus across the globe, especially in the U.S., has been on the combination therapy, Fredrickson said, once again pointing to the STRIDE regimen’s three-year survival data. The Imfinzi-Imjudo combo was approved under FDA priority review.

Also in liver cancer, AZ recently launched the phase 3 Emerald-3 trial testing Imfinzi, Imjudo and transarterial chemoembolization with or without Lenvima in locoregional liver cancer. The combination of Imfinzi, Imjudo and chemotherapy also expects an FDA decision in newly diagnosed non-small cell lung cancer later this year. AZ also has ongoing trials pairing Imjudo with Imfinzi in bladder cancer and small cell lung cancer.

Editor's Note: The story has been updated with additional comments from AstraZeneca's David Fredrickson.