Two Delayed Cancer Vaccine Readouts: Why I Am More Optimistic About AMPLIFY-7P Than REGAL

Disclosure: The author holds beneficial long positions in both Elicio Therapeutics, Inc. (NASDAQ: ELTX) and SELLAS Life Sciences Group, Inc. (NASDAQ: SLS). This article is provided for informational and educational purposes only and is not financial advice. Although the author is a Medical Doctor, this content represents a personal analytical perspective and does not constitute medical advice, a diagnosis, or a treatment recommendation. The author receives no compensation for this article and has no business relationship with either company. Please see the full "Legal Information and Disclosures" section below.

At first sight, Elicio's ELI-002 and SELLAS' galinpepimut-S (GPS) have little in common besides being peptide-based off-the-shelf therapeutic cancer vaccines, as both target entirely different malignant diseases in very different clinical settings. ELI-002 targets mutant KRAS in patients with resected pancreatic ductal adenocarcinoma (PDAC), while GPS targets the Wilms tumor 1 (WT1) protein in patients with acute myeloid leukemia (AML) who have achieved second complete remission (CR2) but are ineligible for transplant. I covered Elicio's approach in depth and recently explored SELLAS' Phase 3 REGAL study.

What connects these two trials is that they are in a similar situation now: both AMPLIFY-7P and REGAL have experienced delayed readouts because events accumulated more slowly than projected. In my Monte Carlo simulation, I explored what that delay may mean for Elicio. Here, I want to step back and compare the two programs on their scientific merits, trial design, and the weight of evidence behind each. I am optimistic about both, but the depth of conviction is not equal.

One thing before discussing why: therapeutic cancer vaccines are historically a graveyard of failed trials.

The case for Elicio's ELI-002 rests on data that I have discussed before. The Phase 1 AMPLIFY-201 trial showed a 15.31-month median relapse-free survival in MRD-positive PDAC patients, against historical controls of roughly 5 to 6 months, and the results were published in Nature Medicine. The Monte Carlo simulation I built around AMPLIFY-7P's delayed readout suggests that efficacy scenarios fitting the observed delay were 2 to 3 times more likely than the null hypothesis. The IDMC recommended continuation without modification in August 2025.

On March 12, 2026, Elicio's annual report reconfirmed the H1 2026 readout, stated that the company remains blinded, and noted that fewer progressions and deaths than projected continue to be observed. Phase 1 oncology signals such as AMPLIFY-201, especially in PDAC, have a dismal track record in randomized settings, and a median from 20 patients carries a wide confidence interval. But the cumulative pattern of delayed events, IDMC continuation, and steady messaging may reflect a real treatment effect.

The scientific rationale for ELI-002 in PDAC draws on a growing body of research linking the local immune system to pancreatic cancer outcomes. We know for more than two decades that CD8+ and CD4+ tumor infiltrating lymphocytes correlate with a favorable prognosis in pancreatic cancer. Mutant KRAS is expressed in over 90% of PDAC tumors. Balachandran et al. demonstrated that neoantigen quality and CD8+ T-cell infiltration jointly predict long-term PDAC survival, and subsequent work from the same group showed evidence of natural immunoediting in PDAC tumors over time.

Elicio's Amphiphile (AMP) platform builds on this biology by conjugating both the KRAS peptide antigens and the CpG adjuvant to lipophilic tails that bind endogenous albumin at the injection site, concentrating them in draining lymph nodes where antigen presentation occurs. The result is strong immunogenicity without the need for checkpoint inhibitors. In AMPLIFY-7P's Phase 1 portion, 99% of evaluable patients mounted mKRAS-specific T-cell responses.

Independent work has added to this picture. In February 2026, Huff, Haldar et al. at Johns Hopkins published in Nature Communications the results of mKRAS-VAX, a pooled synthetic long peptide vaccine combined with dual checkpoint blockade in 12 patients with resected PDAC. As I discussed in my article on that study, the Hopkins trial provided indirect external validation that pooled mKRAS peptides may generate durable, cross-reactive T-cell immunity correlating with disease-free survival. The correlation between T-cell response magnitude and DFS in the Hopkins trial paralleled what Elicio reported in AMPLIFY-201.

In December 2025, Elicio reported evidence of antigen spreading to patient-specific neoantigens beyond mKRAS in the ongoing Phase 2 trial. This, although it comes from a rather small subset, may be the most biologically significant signal of efficacy so far: it suggests that vaccine-induced T cells are killing cancer cells, releasing new antigens, and broadening the immune response beyond what ELI-002 itself targets. If that process holds, antigen spreading could increase both the depth and durability of immunosurveillance.

The question is whether this biological rationale translates into a clinical effect. AMPLIFY-7P's primary endpoint is median DFS, vaccine versus observation, a clean comparison without confounders introduced by the control arm's treatment.

SELLAS' REGAL trial addresses a different disease with a different evidence base. I believe the program carries more uncertainty, though it targets an area of enormous unmet need: there is no approved maintenance therapy for transplant-ineligible CR2 AML patients. The control arm receives best available therapy (BAT), which per the trial protocol may include observation, hypomethylating agents (decitabine or azacitidine), venetoclax, and/or low-dose cytarabine, administered as monotherapy or in combination at the investigator's discretion. This introduces variability that the trial cannot fully control.

The historical data on median overall survival in transplant-ineligible CR2 AML is thin, and much of it comes from company-adjacent sources. The GPS Phase 1/2 matched cohort reported 5.4 months in a historical comparator group. SELLAS cited 6 months in its January 2025 interim analysis press release. A steering committee member estimated around 8 months including HMA and/or venetoclax.

The wider relapsed AML literature points in a similar direction, but each study measured survival from a different starting point and in a different era. Brandwein et al. in the American Journal of Blood Research reported a median OS of 5.3 months from diagnosis of relapsed/refractory AML, not from CR2, using Alberta Cancer Registry data from 2013 to 2016, before venetoclax was available. Bataller et al. in Haematologica found a similar 5.3-month median, again measured from first relapse rather than from CR2, in patients treated at MD Anderson between 2017 and 2022. Van der Maas et al. in Blood Advances described median OS after first AML relapse as traditionally below 6 months, based on the HOVON-SAKK cohort of 943 patients who relapsed after intensive induction. All three capture survival from the point of relapse in heterogeneous populations, not from the point of achieving CR2 and entering maintenance.

The specific benchmark that matters for REGAL, the median OS from CR2 in transplant-ineligible patients receiving modern care, may be longer than these relapse-onset figures suggest. We simply lack robust independent registry data to pin it down.

REGAL's primary endpoint is median overall survival, not DFS. All patients, regardless of arm, may receive any therapy once they relapse. If patients in either arm access effective salvage regimens after relapse, post-relapse treatment could dilute or eliminate any survival difference the vaccine produced during remission. Unlike DFS, which captures a vaccine's direct effect on disease control, OS is shaped by everything that happens after relapse. In a disease where salvage options continue to evolve, that is a meaningful source of noise.

The REGAL trial has passed two IDMC reviews: the formal interim analysis in January 2025 triggered at 60 events, and a periodic review in August 2025. Both resulted in recommendations to continue without modification. These are encouraging signals, but their informational value may be more limited than is often assumed.

Consider a scenario in which GPS has no efficacy. The trial would compare an inert vaccine arm against a BAT arm where some patients might receive active maintenance. At 60 of 80 required events, a truly flat or unfavorable trend would likely have triggered the futility boundary, so the IDMC's recommendation to continue suggests at least some numerical signal favoring GPS. But not crossing a futility boundary is a lower bar than demonstrating efficacy, and a modest trend at interim can still reflect noise rather than a real treatment effect. SELLAS disclosed in December 2025 that only 72 of the required 80 events had occurred, a delay that could reflect either a treatment effect or simply longer-than-expected survival in both arms.

The trial design concerns are one layer. The scientific evidence behind each vaccine introduces another. ELI-002 is grounded in a large body of evidence linking the local immune response to PDAC outcomes, with two independent groups now showing consistent correlations between vaccine-induced mKRAS-specific T-cell responses and disease-free survival. The evidence base for GPS, while promising, is thinner. WT1 is overexpressed in AML blasts, which makes it a rational target. But AML cells may downregulate or lose antigen presentation via MHC class I, which means that even a strong vaccine-induced T-cell response might not always reach its target.

The strongest argument that immune-mediated killing works in AML comes from the graft-versus-leukemia (GvL) effect observed after allogeneic stem cell transplantation. GvL demonstrates that donor T cells can eliminate residual leukemic cells (Beelen et al.), and this is the conceptual foundation that supports GPS. In the transplant setting, though, the immune response is driven by alloreactive donor T cells recognizing a wide array of minor histocompatibility antigens on the recipient's leukemia cells, not just a single protein. GPS contains four WT1 peptide sequences spanning both MHC class I and class II epitopes, which broadens its immunogenic profile. Still, even a multivalent vaccine targeting one parent protein may not replicate the breadth of alloreactive immunity, though it could contribute meaningfully if WT1 presentation is maintained.

Whether that presentation is maintained is a real question, but the answer likely depends on disease state. Christopher et al. found epigenetic downregulation of MHC class II genes at relapse after allogeneic transplantation, and Tian et al. identified a SUSD6-mediated MHC class I degradation pathway in AML blasts. Both studies, however, examined active or relapsed disease where the leukemic burden is high and selective pressure on immune evasion is greatest. REGAL vaccinates patients in CR2, when chemotherapy may have reduced the disease to minimal levels and the immunosuppressive pressure exerted by leukemic blasts might be diminished. With a smaller residual population and potentially less selective pressure driving escape phenotypes, the evasion concern may be overstated for this setting. Importantly, WT1 transcript levels are used clinically as a minimal residual disease marker in AML patients in complete remission, as validated by the European LeukemiaNet standardized assay, which suggests that residual cells may continue to express the target antigen in a low-burden state.

The GPS Phase 1/2 results showed DFS and OS that appeared favorable, and SELLAS reported that T-cell response rates improved from Phase 1/2 to the REGAL interim analysis, with 80% of randomly sampled REGAL patients in the GPS arm showing a specific T-cell immune response. These are encouraging observations. But the Phase 1/2 had no control arm, and the historical comparator was based on retrospective data. The correlation between T-cell response and clinical outcome has not been established prospectively in a randomized setting for GPS the way it has been directionally validated for mKRAS vaccines by two independent groups: Elicio in AMPLIFY-201 and Johns Hopkins in mKRAS-VAX. The mechanistic chain from vaccination to T-cell response to leukemia cell killing has fewer independent data points supporting it.

GPS represents a serious and much-needed attempt to harness the immune system in a disease where transplant-ineligible CR2 patients have no approved maintenance therapy, and a positive readout would be transformative. But when I weigh the evidence, ELI-002 for PDAC sits on stronger ground. It targets an antigen expressed in over 90% of PDAC tumors. It is supported by a substantial body of research linking immune responses to PDAC outcomes. It has received external validation from an independent academic group using a different platform. Its trial design compares vaccine to observation, introducing no confounders from the control arm. And its primary endpoint, DFS, directly captures the vaccine's effect on disease control.

REGAL faces a less well-characterized control arm, an OS endpoint that may be confounded by post-relapse therapy, and thinner mechanistic evidence that WT1-targeted vaccination translates to AML cell killing. Both readouts could surprise in either direction. But the depth of scientific conviction behind the two programs is not equal, and that is why I am more optimistic about Elicio's AMPLIFY-7P.

Follow me on X for frequent updates (@chaotropy).

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