Phanes Therapeutics, Inc., a U.S.-based clinical-stage biotech company, has announced positive results from the Phase 2 portion of its TWINPEAK trial evaluating spevatamig (PT886)—a first-in-class bispecific antibody targeting CLDN18.2 and CD47—in combination with chemotherapy for first-line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). The results, presented at ASCO GI 2026, suggest that spevatamig + GnP (gemcitabine + nab-paclitaxel) may deliver higher response rates and survival outcomes compared to historical controls, while maintaining a favorable safety and tolerability profile
The trial enrolled patients with CLDN18.2-positive mPDAC, a biomarker-driven selection strategy gaining traction in gastrointestinal oncology. In the 2 mg/kg weekly dosing cohort, spevatamig combined with GnP yielded an overall response rate (ORR) of 40%, disease control rate (DCR) of 93%, median progression-free survival (mPFS) of 7.3 months, and a median overall survival (mOS) of 13.2 months, which continues to mature. These results are especially notable given the historical mOS of ~8.5 months with GnP alone in pivotal studies such as MPACT.
What this reveals about CLDN18.2’s growing relevance in pancreatic cancer beyond gastric and GEJ tumors
While CLDN18.2 has been well established as a target in gastric and gastroesophageal junction (GEJ) cancers—primarily through the clinical development of zolbetuximab—its role in pancreatic cancer has remained underexplored. Phanes’ trial pushes this boundary by using a 10% expression threshold (≥2+ staining) for CLDN18.2 positivity, a criterion met by 85% of screened patients.
This prevalence is higher than previously expected and signals a potentially underappreciated therapeutic window in pancreatic tumors, where treatment options are notoriously limited. Pancreatic cancers typically present with dense stromal components and low immunogenicity, limiting the efficacy of many targeted or immunotherapy agents. However, CLDN18.2 expression may help identify a molecularly defined subpopulation more amenable to immune engagement strategies.
If the TWINPEAK results are validated in larger datasets, CLDN18.2 testing could become a standard screening biomarker in mPDAC—akin to HER2 testing in breast and gastric cancers. This could, in turn, lead to expanded commercial relevance for CLDN18.2-directed therapies beyond the gastric setting.
Why dual-targeting with CD47 is both an opportunity and a risk for Phanes
The inclusion of CD47 as a co-target represents both a mechanistic innovation and a regulatory liability. CD47 blockade enhances innate immune activity by promoting macrophage-mediated phagocytosis. However, many CD47-targeting agents have encountered significant toxicity issues, particularly treatment-emergent anemia, thrombocytopenia, and neutropenia, due to the “don’t eat me” signal’s expression on normal red blood cells.
Spevatamig, according to Phanes, employs a native IgG-like molecular format that modulates CD47 binding in a way that spares normal hematologic cells. This is supported by the TWINPEAK data: across 15 patients in the 2 mg/kg QW cohort, no Grade ≥3 anemia, thrombocytopenia, or neutropenia was reported. Moreover, the trial showed no cytokine release syndrome (CRS), a common challenge in bispecific antibody development.
However, dose escalation beyond 2 mg/kg is ongoing, and the higher-dose safety data remain immature. Regulators and clinicians are likely to reserve judgment until Phanes can demonstrate that its platform avoids CD47-related toxicities at pharmacologically relevant exposures. This will be especially critical as combination regimens become more complex—such as with PD-1 inhibitors like pembrolizumab, where overlapping toxicity risks increase.
How spevatamig’s efficacy compares to GnP and FOLFIRINOX in real-world pancreatic care
Phanes’ reported mPFS of 7.3 months and mOS of 13.2 months compare favorably with historical benchmarks. In the MPACT trial (Von Hoff et al., 2013), GnP monotherapy achieved a mPFS of 5.5 months and mOS of 8.5 months. The 40% ORR in spevatamig + GnP contrasts with ~23% ORR in MPACT, suggesting a meaningful potential efficacy delta.
FOLFIRINOX, another commonly used first-line option, shows higher ORR and mOS in fit patients but is less tolerable, especially in older or frailer patients. The tolerability profile of spevatamig—characterized by low GI toxicity, absence of high-grade hematologic events, and no need for dose reductions—may make it a more realistic option for broader real-world populations, including those unable to tolerate FOLFIRINOX.
However, experts caution that non-randomized comparisons remain inherently limited. Without a head-to-head trial or at least propensity-matched external control arms, regulators will be hesitant to draw definitive conclusions about superiority. The path forward may involve either a randomized Phase 2 expansion or formal progression into Phase 3 with survival as a primary endpoint, likely in collaboration with a larger partner.
Why Phanes’ bispecific format is being watched as a platform, not just a single product
Spevatamig is part of a broader wave of bispecific antibody innovation in solid tumors, where dual engagement of tumor antigens and immune checkpoints or innate immunity targets is becoming increasingly attractive. What sets Phanes apart is its platform-centric approach: spevatamig is one of three bispecifics in its pipeline, alongside peluntamig and mavrostobart, each aimed at different combinations of tumor and immune targets.
The company is positioning itself not only as a developer of novel I2Es (innate immunity enhancers) but also as a biotech with a modular architecture capable of building multiple dual-target agents with differentiated safety and manufacturability. Spevatamig’s native IgG-like structure could lower the bar for CMC scalability and regulatory acceptance, compared to more exotic bsAb constructs like tandem scFvs or tri-specifics.
This platform narrative may also be attractive to strategic investors or pharma acquirers looking for bispecific technologies with plug-and-play potential. The clinical collaboration with Merck around the pembrolizumab combo underscores the external validation of this approach. If spevatamig succeeds, it could elevate Phanes’ profile well beyond pancreatic cancer.
What this changes for biotech investors and clinical trial watchers in the GI cancer space
The most immediate impact of this data release is to reposition Phanes as a serious player in pancreatic cancer immunotherapy—a space where very few novel agents have succeeded. Investor sentiment in CD47 programs has been shaky following the discontinuation of multiple trials and the commercial underperformance of Magrolimab. Phanes’ ability to mitigate CD47 toxicity and combine effectively with chemotherapy could renew interest in the target class, particularly in solid tumors.
From a clinical strategy perspective, the trial also offers a template for how to de-risk bispecific development in difficult-to-treat cancers: start with a tolerability-optimized design, focus on biomarker-enriched populations, and combine with chemotherapy rather than replace it. This pragmatic approach may resonate with both regulators and community oncologists looking for realistic stepwise improvements rather than moonshot cures.
The ongoing expansion into China-based trials suggests a global regulatory ambition, and future data from these populations will help clarify whether spevatamig’s performance is consistent across ethnic and regional cohorts—a key concern for multiregional drug development in oncology.
What happens next and what risks still need to be managed
There are still several unknowns that could derail or delay Phanes’ progress. The most critical is dose-dependent safety. The company must prove that higher doses (3 mg/kg and above) do not introduce unacceptable toxicity. Should adverse events emerge, especially hematologic or immune-mediated, the favorable early profile may not hold.
Another issue is regulatory alignment on biomarker definitions. If CLDN18.2 testing becomes mandatory, Phanes will need to ensure diagnostic access and reimbursement. Alternatively, if efficacy can be shown in CLDN18.2-low populations, the drug’s market size would significantly increase—but at the cost of requiring more complex trial designs.
Finally, competition is intensifying. While zolbetuximab remains focused on gastric cancer, other bispecific and ADC (antibody–drug conjugate) players are eyeing pancreatic cancer with different mechanisms. Phanes’ first-mover advantage in dual CLDN18.2/CD47 targeting may not last unless the company accelerates its late-stage planning.
Phanes’ spevatamig shows 40% response rate in mPDAC: How it compares to GnP standard added by Pallavi Madhiraju on
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