Vaccines, Next-Gen Approaches Target the Toughest Cancers: AACR

2024-04-12

临床1期ASCO会议疫苗AACR会议临床结果

Pictured: Gloved hands amid a collage of cancer treatments/Taylor Tieden for BioSpace Parsing key trends from 7,200 abstracts on cancer-related research can be challenging—take it from someone who’s spent the past week trying to do it! But pretty quickly, a few key themes became apparent at the American Association for Cancer Research’s annual meeting. First and foremost, the programs presented are tackling difficult cancers with a high unmet need and a dire prognosis. Some of the presentations last weekend involved drug candidates targeting pancreatic cancer, for example. In 2023, the five-year survival rate for pancreatic cancer was just 12%, according to the American Cancer Society. Two presentations—one on Bristol Myers Squibb’s blockbuster immunotherapy Opdivo, the other on a messenger RNA vaccine in development by BioNTech and Genentech—showed promising signals. Opdivo’s trial, the first reported of a PD1 inhibitor in neoadjuvant pancreatic cancer, indicated that the drug may improve outcomes, while BioNTech and Genentech’s vaccine continued to show potential in a particularly difficult-to-treat form of the disease. This announcement also dovetailed with another prominent theme at AACR: the resurgence of cancer vaccines, which are also making inroads in advanced liver cancer, head and neck cancer, non-small cell lung cancer and glioblastoma. Glioblastoma is a particularly aggressive form of brain cancer that carries a 5-year survival rate of just 10%; patients typically survive between 15 and 18 months after being diagnosed. A Phase I study of Diakonos Oncology’s dendritic cell vaccine showed “substantially increased survival” in glioblastoma patients; 88% of patients remained alive a year after treatment, compared to a historical 53% of those on standard regimens. Other platforms and approaches also appear to be breaking through against difficult-to-treat cancers, though many of the results presented at AACR are still early stage. As anticipated, antibody-drug conjugates (ADCs) were a focus, with Vincerx Pharma presenting Phase I data in metastatic tumors and Merck and Kelun-Biotech reporting a potential survival benefit from their TROP2-directed ADC in gastric cancer. Several other modalities were also on display at AACR. Phase I data from Menlo Park, Calif.–based Synthekine, for example, showed that its α/β biased interleukin-2 (IL-2) partial agonist interleukin-2 (IL-2) partial agonist, STK-012, has thus far avoided the toxicities associated with IL-2 therapies while also demonstrating a “favorable” efficacy pro advanced solid tumors. And TILT Biotherapeutics reported that TILT-123, an oncolytic adenovirus armed with tumor necrosis factor alpha and IL-2, “demonstrated signs of efficacy” when combined with Merck’s Keytruda in a Phase I trial in patients with platinum-resistant and refractory ovarian cancer. Another therapy that drew attention at the meeting was AstraZeneca’s next-generation poly-ADP ribose polymerase 1 (PARP1) selective inhibitor, which experts are hopeful can negate some of the toxicities caused by drugs that inhibit both PARP1 and PARP2. Timothy Yap, vice president and head of clinical development in the Therapeutics Discovery Division at The University of Texas MD Anderson Cancer Center, noted in his presentation of the positive Phase I/II trial data that there is a “great opportunity” to combine a selective PARP1 inhibitor PARP1 inhibitor with other therapies. This was a point also made by David Weinstock, vice president of discovery oncology at Merck, who in March told BioSpace that we are moving toward a future “where we have enough medications that each work individually and have minimal side effects so that we can create even larger combinations, which offer the most benefit to people.” As a science journalist, it’s easy to get bogged down in the data, the results and biggest trends (ADCs for all!) and forget the human face of cancer. As a human being, it’s easy to get depressed by improvements that might seem incremental, but an additional six months can mean another birthday, another anniversary or the birth of another grandchild. Elevation Oncology CSO David Dornan told me that solid cancers “are almost equally as hard and different in their own right.” But progress is being made. In 2023, the five-year survival rate for pancreatic cancer increased by one percentage point from the previous year, marking the second year in a row survival has increased. Overall, the cancer death rate in the U.S. has declined by 33% since 1991. I, for one, am looking forward to reading about the next advances at the American Society of Clinical Oncology’s annual meeting in June. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.