August 28, 2025
3 min read
Key takeaways:
- Vaccine could improve survival for patients with pancreatic and colorectal cancers.
- Vaccine targets mutant KRAS and could be applicable to other cancer types.
A novel, off-the-shelf vaccine that targets KRAS mutations could dramatically improve the “dismal” outlook patients with pancreatic cancer face after relapse.
Final results of a phase 1 investigation showed individuals who developed strong T-cell responses to mutant KRAS from the vaccine — ELI-002 2P (Elicio Therapeutics) — did not reach a median RFS or OS after nearly 20 months of follow-up.
The vaccine could have an impact on other tumors with KRAS mutations, too, including colorectal cancer.
“We’re really excited about what we see so far,” Zev A. Wainberg, MD, professor of medicine and co-director of the GI oncology program at UCLA, told Healio.
‘High risk of recurrence’
Between 20% and 25% of solid tumors have KRAS mutations, particularly in pancreatic ductal adenocarcinoma (93%) and colorectal cancer (50%), according to study background.
“The group of patients, particularly those who have pancreatic cancer but any KRAS-driven cancer, even after they’re done with therapy, tend to have a high risk of recurrence,” Wainberg said. “There’s this period in time in which you treat them with everything you have, and then you’re just watching, but unfortunately the cancer has a tendency to recur.”
Patients with pancreatic ductal adenocarcinoma (PDAC) who relapse following surgery and chemotherapy have a 5-year survival of 23.3%, often prompting health care providers to prioritize palliative care.
“It’s really dismal,” Wainberg said. “Even for patients who have very early-stage pancreatic cancer who are resected and then treated with chemotherapy, we are still anxious the cancer will recur.”
Researchers developed ELI-002 2P, which targets KRAS mutations G12D and G12R, to improve these numbers.
The study included 25 patients with surgically resected PDAC (80%) or colorectal cancer.
Safety served as the primary endpoint. RFS and OS served as secondary endpoints.
Healio previously reported on safety and early results of the dose-escalation portion of the investigation. The most common toxicity was injection site reaction. No participants developed grade 3 or worse adverse events and no one experienced any dose-limiting toxicities. Additionally, 84% of patients had a KRAS-specific immune response.
‘A real finding’
At median follow-up of 19.7 months, researchers did not observe any new toxicities.
Overall, the cohort had a median RFS of 16.33 months and median OS of 28.94 months, but those who had strong mutant KRAS responses had significantly better outcomes than those with weak responses.
Participants who had a T-cell fold-change greater than 9.17 (68%) had significantly improved median RFS (not reached vs. 3.02 months; P = .0002) and OS (not reached vs. 15.98 months; P = .0099).
“Historical control for recurrence in people with a high tumor marker or high ctDNA after treatment is very poor — it’s under 6 months to 9 months,” Wainberg said.
“The group of patients who have that immune response [to the vaccine], very few of them recurred, and all of them were still alive at the point of the data analysis,” he added. “That to me is quite encouraging.”
Among patients who had strong T-cell response, 65% had no radiographic progression.
Additionally, minimal residual disease cleared in six patients (PDAC, n = 3; colorectal cancer, n = 3).
“What you want to see in these studies is durability, sustainability,” Wainberg said. “When you take a look 6 months after a study starts, you’re starting to think about something good happening, but then when you look at this extended period, you start to be reassured that this is a real finding. We looked at 20 months, which is a pretty long time in this disease. I think it is a real finding.”
Researchers also found 67% of tested patients had T-cell responses not associated with KRAS.
“When we looked at the features of the T-cell responses, a lot of these so-called bystander T cells were getting involved,” Wainberg said.
Wainberg emphasized the results are from a phase 1 trial, and more data are needed.
Researchers have already concluded a randomized phase 2 trial that included approximately 150 patients with PDAC. They randomly assigned patients 2:1 to receive the vaccine or undergo standard observation.
Wainberg and colleagues expect to have findings in the first quarter of 2026.
“We’re eagerly awaiting the results,” Wainberg said.
If those results show the vaccine does improve survival, future investigations could involve testing the vaccine in other KRAS-mutant tumors.
“We’re cautiously optimistic,” Wainberg said. “We see something really positive.”
For more information:
Zev A. Wainberg, MD, can be reached at [email protected].
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Sources/Disclosures
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Disclosures:
Elicio Therapeutics funded the study. Wainberg reports consultant/advisory fees from Alligator Bioscience, Amgen, Arcus, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Ipsen, Lilly Oncology, Macrogenics, Merck, Merck KGaA, Novartis, Pfizer, PureTech, Roche and Seagen; and research funding from Arcus, Elicio Therapeutics, Five Prime Therapeutics, Merck, Novartis, Pfizer and Plexxikon. Please see the study for all other authors’ relevant financial disclosures.
