Each June, physicians and scientists from the global cancer community convene in Chicago for one of the largest medical meetings of the year. The annual meeting of the American Society of Clinical Oncology (ASCO) drew more than 40,000 people to McCormick Place this year, but it was not the biggest Chicago event of the past week. That honor belongs to Taylor Swift.
Swift played three nights at Soldier Field, only a few blocks from McCormick Place. The stadium has a concert capacity of 63,500 and the venue said each night was sold out. On three consecutive evenings, ASCO attendees streaming from the convention center encountered Swifties who filled buses, trains, and sidewalks. By all accounts, the interaction was well tolerated and there were no reports of serious adverse effects. (At one hotel, glitter spillage was observed in a hallway but this is believed to be an isolated incident.)
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Within McCormick Place’s cavernous rooms, physicians and scientists heard clinical trial data presentations that in some cases, could change the practice of treating certain cancers. Here’s a recap of some highlights from this year’s ASCO annual meeting.
Moving ahead in line
Carvykti, from Legend Biotech and Johnson & Johnson subsidiary Janssen, posted clinical data that support moving the cell therapy into earlier lines of multiple myeloma treatment. The therapy won FDA approval last year as a fifth-line therapy for multiple myeloma. Additional clinical data presented at the ASCO meeting showed that the cell therapy reduced the risk of disease progression by 74% in patients who no longer response to multiple myeloma drug Revlimid, compared to two standard of care drug combinations. Study participants had previously received one to three lines of prior treatment.
The results came from patients with a median follow up of 16-months. In the Carvykti arm, median progression-free survival has not yet been reached. In the standard of care arm, median progression-free survival was 11.8 months. As of the cutoff date for the data, the Carvykti arm showed an 85% overall response rate with 73% of patients in the group achieving complete response to the therapy.
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In an interview, Legend CEO Ying Huang said the results support his company’s belief that Carvykti is best in its class. The cell therapy is made by engineering a patient’s T cells to go after BCMA, a protein abundant on multiple myeloma cells. Bristol Myers Squibb’s approved cell therapy Abecma also binds to this target. But Huang says Carvykti stands apart with a “tandem design” in which the therapy binds to two different places on the BCMA protein, enabling it to bind to the target better.
“They form a very stable complex with BCMA,” Huang explained. “Because they form such a stable complex, it does not dissociate. Once they find BCMA, they latch on and they don’t dissociate.”
The results showed no new safety signals. In fact, the cytokine release syndrome and neurotoxicity that are known complications with CAR T-cell therapies were reported with less frequency in this study compared with previous clinical tests. Huang said the difference is that in earlier lines of therapy, patients have not been treated for a long time with immunosuppressive therapies. These patients are less sick and have a lower tumor burden compared with those who had entered clinical testing at a more advanced stage of their disease.
With the latest clinical trial results for Carvykti in hand, Janssen and Legend are seeking to expand regulatory approvals to include earlier lines of treatment. Soon after the data presentation at ASCO, Janssen submitted an application seeking to expand Carvykti’s FDA approval to patients who had received at least one earlier line of therapy. Janssen had already submitted an application in late May seeking to expand Carvykti’s approval in Europe.
ADCs ascending
Elahere, an ImmunoGen drug that won accelerated FDA approval last fall for treating ovarian cancer, posted results from a confirmatory Phase 3 study that support full approval of the drug. Clinicians said the results could change the practice of treating ovarian cancer, adding that the drug could become the standard of care for certain patients.
Elahere is an antibody drug conjugate (ADC), a type of therapy comprised of a toxic cancer-killing drug payload linked to a targeting antibody. The ImmunoGen drug’s target is folate receptor alpha, a protein found on ovarian cancer cells.
Accelerated approval of Elahere covers the treatment of patients whose ovarian cancer expresses high levels of folate receptor alpha. The Phase 3 results reported at the ASCO meeting showed treatment with Elahere led to 36% better progression-free survival and 26% better overall survival compared with the physician’s choice of chemotherapy. Based on those results, ImmunoGen said it plans to seek full FDA approval of Elahere and approval in Europe later this year.
Other ADCs posted promising clinical trial results at the ASCO meeting. Enhertu, the AstraZeneca and Daiichi Sankyo ADC whose breast cancer data made it one of the big newsmakers of last year’s convention, posted interim data from a mid-stage study that could support expanding use of the drug to a wider range of HER2-expressing cancers.
Enhertu’s current FDA approvals are for gastric cancer, lung cancer, and breast cancer. An ongoing Phase 2 study is testing this ADC in seven other types of cancer that also express HER2. The 57.5% objective response rate in endometrial cancer was the highest, but investigators noted that these rates were high for almost all of the other groups. The exception was pancreatic cancer, which showed an objective response rate of just 4%. As the study continues, investigators expect to obtain data for overall survival and progression-free survival.
In other ADC news, data reported from a partner’s early-stage study in China are positioning Elevation Oncology to move forward with its own study. The drug is an ADC that targets Claudin 18.2, a protein that’s heavily expressed in gastric, pancreatic, and esophageal cancers. At the ASCO meeting, Hong Kong-based CSPC Pharmaceutical Group reported encouraging results from a dose-escalation Phase 1 study in China testing the drug in patients with solid tumors that have become drug resistant or have not responded to earlier treatments. In 17 evaluable gastric cancer patients, investigators reported an objective response rate of 47.1% and a disease control rate of 64.7%.
Last year, Elevation licensed rights to CSPC’s ADC, now called EO-3021. Those rights cover the world, except for Greater China, where CSPC retains rights. Joe Ferra, interim CEO and chief financial officer of Elevation, told MedCity News that CSPC’s data lend validation to the drug and also give his company a head start. Usually, a biotech enters Phase 1 study knowing little about the right dose for its drug. But thanks to CSPC’s clinical data, Elevation heads to the clinic already knowing what dose is efficacious. Elevation’s Phase 1 study is on track to begin in the second half of this year, Ferra said.
Advances in adjuvants
Adjuvants, drugs used to catch cancer cells missed by the initial treatment and to keep the cancer from coming back, saw some promising developments at the ASCO meeting. AstraZeneca’s osimertinib, brand name Tagrisso, previously posted Phase 3 data showing it improved disease-free survival, a measure of how long patients live without again showing signs of the cancer. Now the pill has additional Phase 3 results showing the therapy helps patients live longer. Those results could help drive sales of Tagrisso, whose more than $5.4 billion in annual revenue makes it far and away AstraZeneca’s top-selling product.
Tagrisso is a small molecule that blocks the cancer-driving protein EGFR. In 2020, the drug’s approval was expanded to include use of the drug as an adjuvant therapy for early-stage NSCLC driven by a particular EGFR mutation. According to results presented at this year’s conference, 88% of patients treated with the AstraZeneca drug as an adjuvant were alive five years after initially receiving the treatment compared to 78% of those who received a placebo. Median overall survival has not yet been reached in either group. Those who received placebo and showed a recurrence of cancer were offered the opportunity to receive Tagrisso.
“Osimertinib is the first targeted therapy to show significant overall survival benefit in the adjuvant setting,” Yale University’s Dr. Roy Herbst, the principal investigator of the Phase 3 study, said in the ASCO presentation of the results. “These findings reinforce adjuvant osimertinib as standard of care for patients with resected EGFR-mutated stage IB to IIIA non-small cell lung cancer and highlight the importance of screening and EGFR mutation testing as early as possible to broaden treatment access for patients.”
Meanwhile, Novartis reported Phase 3 data that support bringing its blockbuster breast cancer drug Kisqali into wider use. The drug is currently approved for treating advanced and metastatic breast cancers that are HR positive and HER2 negative. The data reported at the ASCO meeting are from a Phase 3 test that evaluated the Kisqali as an adjuvant. The Novartis drug was tested in combination with an endocrine therapy and compared to treatment with endocrine therapy alone.
Data from the study showed the drug combination lowered the risk of cancer recurrence by 25.2% in patients with early breast cancer that is HR positive and HER2 negative. Novartis said these results have the potential to more than double the number of patients who could benefit from Kisqali as an adjuvant therapy. The Swiss pharma giant said it planned to submit the Phase 3 data to U.S. and European regulators by the end of this year.
A cancer vaccine from Moderna is also being positioned as part of an adjuvant drug regimen. Moderna and partner Merck released Phase 2b results showing that mRNA-4157, their messenger RNA vaccine candidate for melanoma, helped patients live longer without distant metastasis, the spread of cancer beyond its initial site. The Moderna cancer vaccine is made by sequencing a patient’s tumor to identify the tumor-related antigens, or neoantigens, that will prompt an immune response to the cancer. The vaccine itself is comprised of mRNA designed to express those neoantigens.
The clinical trial paired the cancer vaccine with Merck’s blockbuster immunotherapy, Keytruda. That combination was compared to treatment with Keytruda alone. The Merck drug’s approved indications in melanoma include use of the immunotherapy as an adjuvant. In April, results announced during the American Association for Cancer Research annual meeting showed the treatment combination met the main goal of recurrence-free survival, defined as the time measured from the first dose of Keytruda until recurrence of the cancer. At the ASCO meeting, Moderna reported the treatment combination reduced the risk of distant metastasis or death by 65%, achieving a secondary goal of the study.
Moderna and Merck now plan a Phase 3 test that will evaluate the treatment combination as an adjuvant for high-risk melanoma. This study will start later this year. The partners also plan additional tests of the mRNA-4157/Keytruda combination in other tumor types, including non-small cell lung cancer.
Breaking barriers in brain cancer
Current therapeutic interventions for diffuse gliomas include radiation or chemotherapy, both of which bring about dangerous complications without offering a cure for the brain cancer. An experimental Servier Pharmaceuticals drug has Phase 3 data suggesting the small molecule could provide a treatment alternative.
The Servier drug, vorasidenib, penetrates the blood-brain barrier to block two enzymes that when mutated, contribute to the progression of gliomas. According to results presented at the ASCO meeting, the once-daily pill reduced the risk of tumor progression or death by 61% compared to a placebo. One potential drawback to vorasidenib was the report of elevated levels of liver enzymes in 9.6% of patients who received the drug. Those enzyme levels could be a sign of drug toxicity.
During the BIO International Convention in Boston later in the week, I talked about the study results with Alice Lin Pomponio, managing director of BrightEdge, the investment arm of the American Cancer Society. She said brain cancers remain a huge unmet need due to the challenge of finding and hitting the right targets, adding that it has also been difficult to develop molecules capable of penetrating the blood-brain barrier. Vorasidenib’s ability to do both is promising, she added. As for the potential liver toxicity, Pomponio said the FDA may take a favorable view of the drug given the few treatment options currently available for these brain cancer patients. After the release of the Phase 3 data, Servier said it plans to discuss with the FDA an application seeking regulatory approval.
Photo: John Walton/PA Images, via Getty Images
