In a striking testament to the rapid evolution of cancer treatment, two promising new therapies have emerged from recent clinical trials, offering hope to patients with some of the most challenging blood and solid tumors. At major medical conferences in late 2025 and early 2026, researchers unveiled early but encouraging results for novel combination regimens in mantle cell lymphoma (MCL) and metastatic pancreatic ductal adenocarcinoma (mPDAC)—two malignancies notorious for poor prognoses and limited frontline options.
During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, held from December 6 to December 9, 2025, in Orlando, Florida, Anita Kumar presented preliminary findings from a phase II clinical trial examining a triplet regimen of zanubrutinib, obinutuzumab, and venetoclax (collectively known as BOVen) as a first-line therapy for older patients with MCL. According to the Lymphoma & CLL Hub, the study enrolled 50 older adults, aiming to evaluate the 3-year progression-free survival (PFS) as its primary endpoint.
The results, though early, were impressive. The overall metabolic response rate reached a remarkable 98%, with 96% of patients achieving a complete metabolic response and 2% a partial response. After a median follow-up of 25 months, the 2-year PFS stood at 86% (with a 95% confidence interval of 77–97), and the 2-year overall survival (OS) was 92% (95% CI, 84–100). Notably, 93% of patients (28 out of 30 tested) achieved undetectable measurable residual disease (MRD) at the stringent threshold of 10^-6 at the end of treatment. This MRD negativity is considered a strong predictor of long-term remission in lymphoma.
Importantly, the BOVen regimen was generally well tolerated by the older patient cohort, with grade 3 or higher adverse events occurring in 42% of participants. While this is not insignificant, it compares favorably with toxicities seen in many standard regimens for MCL, which often preclude the use of intensive chemotherapy in older adults. As summarized by the Lymphoma & CLL Hub, these findings suggest that the MRD response-adapted BOVen triplet could represent a major step forward for this difficult-to-treat population—though, as always, longer-term follow-up and randomized data will be needed to confirm these benefits.
Meanwhile, across the country at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) 2026 in San Diego, Phanes Therapeutics announced the first public release of clinical data for its novel agent spevatamig (PT886) in combination with chemotherapy as a frontline treatment for patients with metastatic pancreatic cancer. The TWINPEAK study, a multi-cohort phase 1/2 trial (NCT05482893), is evaluating spevatamig—a first-in-class bispecific antibody targeting claudin 18.2 (CLDN18.2) and CD47—in patients with a range of gastrointestinal carcinomas. As of December 12, 2025, 107 patients had been treated in the United States, including 42 with mPDAC who received spevatamig plus gemcitabine and nab-paclitaxel (GnP) at various dosing regimens.
According to a press release from Phanes Therapeutics, data presented at the meeting focused on the 2 mg/kg weekly dose of spevatamig combined with GnP in 15 patients with first-line mPDAC. The safety profile was notably favorable: no cytokine release syndrome (CRS), no dose-limiting toxicities (DLTs), and no grade 3 or higher treatment-emergent anemia, neutropenia, thrombocytopenia, nausea, or vomiting were observed. There were also no dose reductions or treatment discontinuations due to gastrointestinal side effects—an important consideration in this frail patient group.
Efficacy signals were also encouraging. At this dose level, the disease control rate (DCR) was 93%, and the overall response rate (ORR) was 40%, with six out of fifteen patients achieving a partial response (one pending confirmation). The median progression-free survival (mPFS) was 7.3 months, with a 6-month PFS rate of 59%. The median overall survival (mOS) was 13.2 months and still maturing, while the 6-month OS rate reached 93%. Notably, responses were seen across all patients whose tumors had CLDN18.2 expression of at least 10%—a biomarker present in 85% of those screened. This could potentially expand the eligible population for this therapy.
Spevatamig distinguishes itself not just through its efficacy but also its innovative mechanism. As a native IgG-like bispecific antibody, it simultaneously targets CLDN18.2, a tight junction protein highly expressed in certain gastrointestinal cancers, and CD47, a "don’t eat me" signal that protects cancer cells from immune attack. By blocking both, spevatamig aims to enhance innate immunity against tumors. The drug has already attracted regulatory attention: the U.S. Food and Drug Administration granted it orphan drug designation for pancreatic cancer in 2022 and Fast Track designation in 2024 for metastatic claudin 18.2-positive pancreatic adenocarcinoma.
Phanes Therapeutics is also exploring spevatamig in combination with Merck’s anti-PD-1 therapy pembrolizumab, reflecting a broader trend in oncology toward multi-modal immunotherapy. The TWINPEAK study remains ongoing, with additional data expected as higher dosing regimens mature and as the study expands internationally, including a Phase 2 trial now underway in China.
Both the BOVen and spevatamig regimens underscore a new paradigm in cancer care: personalizing therapy based on molecular markers and combining agents to maximize efficacy while minimizing toxicity. For patients with MCL and mPDAC—diseases that have long defied durable responses to standard treatments—these early results offer a glimmer of hope.
Still, experts caution that it is too soon to declare victory. While the high rates of response and disease control are exciting, the true test will be whether these benefits translate into longer survival and improved quality of life in larger, randomized trials. The oncology community will be watching closely as more mature data emerges in the coming years.
For now, the message from the ASH and ASCO GI meetings is clear: innovation in cancer therapy is accelerating, and patients with even the most formidable tumors may soon have better options on the horizon.
