mitazalimab (ADC-1013) / Alligator Biosci - LARVOL DELTA

Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre phase 1b/2 study. (PubMed, Lancet Oncol) - P1/2 | "Mitazalimab with mFOLFIRINOX demonstrated manageable safety and encouraging activity, warranting continued development in a phase 3, randomised, controlled trial. The results from OPTIMIZE-1 pave the way for further exploration and confirmation of a novel immunotherapy treatment regimen for metastatic pancreatic ductal adenocarcinoma, which is a complex and aggressive cancer with very low survival rates and restricted treatment options."

Journal • Metastases • P1/2 data • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Thrombocytopenia • CD40

Efficacy and safety of mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): An interim analysis of the optimize-1 phase 1b/2 study. (ASCO 2023) - P1b/2 | "OPTIMIZE-1 (NCT04888312) is a Phase 1b/2, open label, multicenter study designed to evaluate safety, tolerability, and efficacy of mitazalimab in combination with mFOLFIRINOX (Oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2, 5-FU 2.4 g/m2) in patients (pts) with previously untreated mPDAC... Mitazalimab + mFOLFIRINOX is a feasible regimen with a manageable safety profile. Mitazalimab administered at 900 µg/kg in combination with mFOLFIRINOX shows encouraging antitumor activity in mPDAC, meriting continued development. The study passes futility and continues to full accrual."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Acute Kidney Injury • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Immune Modulation • Infectious Disease • Nephrology • Neutropenia • Oncology • Pain • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Pneumonia • Renal Disease • Respiratory Diseases • CD40 • IFNG

CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: Biomarkers associated with outcomes from OPTIMIZE-1. (PubMed, Cell Rep Med) - P1/2 | "These results may inform future patient stratification strategies supporting a planned randomized confirmatory trial of mitazalimab with mFOLFIRINOX in mPDAC. This study was registered at ClinicalTrials.gov (NCT04888312)."

Biomarker • IO biomarker • Journal • Fibrosis • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40

CD40 agonist mitazalimab + mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Final efficacy analysis of the OPTIMIZE-1 study. (ASCO-GI 2026) - P1/2 | "Mitazalimab (900 µg/kg) in combination with mFFX continues to show clinically meaningful survival benefits compared with historical controls. Together with a promising duration of response and encouraging long-term survival rates in previously untreated mPDAC patients, these findings support the continued development of mitazalimab in a confirmatory Phase 3 study. Efficacy outcomes."

Clinical • IO biomarker • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

Evaluating the relative treatment efficacy of CD40 agonist mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) using unanchored indirect treatment comparisons (ITCs). (ASCO-GI 2025) - P1 | "Literature based ITCs show a significantly better efficacy of mitazalimab + mFFX versus the current available therapies in patients with mPDAC. These trends will have to be confirmed in a randomized Phase 3 study. 1."

Clinical • Combination therapy • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

CD40 agonist mitazalimab combined with mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Primary analysis of the OPTIMIZE-1 phase Ib/II study (ESMO-GI 2024) - P1/2 | "The OPTIMIZE-1 study met its primary endpoint, with a manageable safety profile and promising DoR associated with a clinically meaningful survival benefit. Furthermore, the NKT & T cell activation profile is strongly suggestive of mitazalimab's contribution to deep anti-tumor responses. These encouraging results warrant continued development in a randomized phase 3 study."

Clinical • IO biomarker • Metastases • P1/2 data • Tumor mutational burden • Anemia • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Thrombocytopenia • CD40 • CD8 • TMB

Precision immunotherapy in metastatic pancreatic cancer: OPTIMIZE-1 biomarker-driven patient stratification for future studies. (PubMed, Ann Pancreat Cancer) - No abstract available

Biomarker • IO biomarker • Journal • Oncology • Pancreatic Cancer • Solid Tumor

On 23 July 2026 Alligator announced that it will discontinue all further independent development of mitazalimab, including preparations for and support of Phase 3 studies, and refocus on preserving the future royalty potential of its financial interest in the out-licensed HLX22 programme. (Alligator Bioscience Press Release) - "Alligator intends to continue to supply mitazalimab to ongoing externally funded investigator-initiated studies, including the randomised Phase 2/3 study in biliary tract cancer, subject to available funding. Alligator also intends to seek to out-license or divest mitazalimab as a broader immuno-oncology asset in the near term."

Discontinued • Pipeline update • Biliary Tract Cancer

Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: University of California, San Diego | Trial completion date: Aug 2029 ➔ Aug 2030 | Trial primary completion date: Aug 2027 ➔ Aug 2028

Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

CD40 agonist mitazalimab + mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Final efficacy analysis of the OPTIMIZE-1 study. (ASCO 2026) - P1/2 | "Mitazalimab (900 µg/kg) in combination with mFFX continues to demonstrate clinically meaningful survival benefits compared with historical controls. The robust duration of response and encouraging long‑term survival—six patients surviving >36 months—support continued development of mitazalimab in a confirmatory Phase 3 study. Table 1"

Clinical • IO biomarker • Metastases • Oncology • Pancreatic Ductal Adenocarcinoma • CD40

Window Study of Intratumoral Mitazalimab in Breast Cancer (WINIT-BC) (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Jennifer Zhang | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Irreversible electroporation (IRE) with intratumoral CD40 antibody increases T-cell reactivity to personalized neoantigens in locally advanced pancreatic cancer (AACR 2026) - P1 | "Mitazalimab, a second-generation CD40 agonistic IgG1 mAb, had promising clinical activity when delivered systemically in combination with chemotherapy in metastatic PDAC... Unbiased, personalized IPV analysis confirms the presence of NeoAg-specific responses against multiple mutations, which are diversified after treatment with IRE and CD40 agonism. The evaluation of additional patients and correlation with clinical outcomes are ongoing."

IO biomarker • Metastases • Tumor-specific neoantigens • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40 • IFNG

Mitazalimab, a potent CD40 agonist in combination with FOLFIRINOX demonstrates changes consistent with increased immune activation in TME and peripheral blood in a preclinical pancreatic cancer tumor model (AACR 2024) - P1/2 | "The combination of mitazalimab and FOLFIRINOX resulted in an increased tumoricidal immune profile, including a marked increase in effector CD8+ T cells compared to the individual therapies. Overall, these preclinical data support the chosen dosing regimen of mitazalimab and modified FOLFIRINOX in the OPTIMIZE-1study and underline the synergistic potential of this combination for an improved antitumor response."

Combination therapy • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40 • CD8

IGNITE: Maintenance Combinatorial Myeloid Immunotherapy for Unresectable Pancreatic Cancer (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: University of Pennsylvania | Trial completion date: Aug 2027 ➔ Dec 2028 | Trial primary completion date: Feb 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

CROCOBIL: Testing Mitazalimab in Combination With Standard Chemotherapy in Immunotherapy Resistant Advanced Biliary Tract Cancers (clinicaltrials.gov) - P2/3 | N=160 | Not yet recruiting | Sponsor: UNICANCER

New P2/3 trial • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor

Window Study of Intratumoral Mitazalimab in Breast Cancer (WINIT-BC) (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Jennifer Zhang

New P1 trial • Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Alligator Bioscience…announced that new data from its Phase 1b/2 OPTIMIZE-1 study evaluating mitazalimab in combination with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC) will be presented at the ASCO Gastrointestinal Cancers Symposium (ASCO GI)… (Alligator Bioscience Press Release) - "The presentation will highlight new analyses from OPTIMIZE-1 further characterizing the clinical benefit observed with mitazalimab plus standard chemotherapy in metastatic pancreatic cancer."

P1/2 data • Pancreatic Ductal Adenocarcinoma

IGNITE: Maintenance Combinatorial Myeloid Immunotherapy for Unresectable Pancreatic Cancer (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: University of Pennsylvania | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Alligator Bioscience announces publication of REACtiVe-2 Phase 1 trial data in Nature Communications (Alligator Bioscience Press Release) - "Key findings: The combination therapy significantly decreased intratumoral collagen content, likely through mitazalimab-mediated macrophage activation and stromal degradation. Treated tumors showed a clear rise in intratumoral T cells, indicating improved recruitment and immune access to the tumor....Patients with stable disease after prior chemotherapy achieved a median OS of 12.1 months and a 1-year survival rate of 50%."

P1 data • Pancreatic Ductal Adenocarcinoma

REACtiVe-2: phase I evaluation of dendritic cell vaccination and agonistic CD40 therapy following (m)FOLFIRINOX in metastatic pancreatic cancer. (PubMed, Nat Commun) - P1 | "In conclusion, MesoPher/mitazalimab combination therapy is safe and tolerable in patients with metastatic PDAC and enhances systemic immune activation and local immune responses. Future research should evaluate the efficacy of this promising approach as maintenance therapy shortly after completing chemotherapy."

Journal • P1 data • Immune Modulation • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40

Alligator Bioscience Presents New Data on Mitazalimab…at SITC 40th Anniversary Annual Meeting (ACCESS Newswire) - "The mitazalimab abstract presents new data from the OPTIMIZE-1 trial in metastatic pancreatic cancer....Key findings: (i) Improved survival outcomes at 6 months: PFS: 50.8% vs. 38.7%; OS: 89.5% vs. 69.4%; (ii) Manageable safety profile : Safety was manageable across both dose levels, with the increased rate of adverse events in the 900 μg/kg group attributed to extended treatment exposure; (iii) Biomarker analyses : Greater immune activation at 900 μg/kg, including higher levels of Ki67+ T cells, a marker of actively dividing and proliferating immune cells."

P1/2 data • Pancreatic Ductal Adenocarcinoma

CD40 agonist mitazalimab + mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma: dose characterization based on exposure response and biomarker analysis from the OPTIMIZE-1 study (SITC 2025) - "The analyses of safety endpoints suggest a higher probability of an event with higher exposure of mitazalimab, but this may be confounded by the combination treatment with mFOLFIRINOX.Conclusions The exposure-response data further supports mitazalimab contribution to the clinical benefits observed in OPTIMIZE-1. Based on available nonclinical and clinical mitazalimab data, a dose of 900 μg/kg is selected for the planned Phase 3 study.Ethics Approval OPTIMIZE-1 was single-arm, phase 1b/2 study conducted in 14 university hospitals in Belgium, France, and Spain according to the study protocol and amendments approved by local Institutional Review Boards and independent ethics committees, and in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines as defined by the International Conference on Harmonisation."

Biomarker • Clinical • IO biomarker • Metastases • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

Comparative Efficacy and Safety of Chemotherapeutic, Targeted, and Immunotherapy Drugs for Pancreatic Ductal Adenocarcinoma Treatment: A Network Meta-Analysis of RCTs (ACG 2025) - "Our analysis included 33 RCTs with a total sample size of 9,239 participants, comprising 5,636 in the treatment group and 3,603 in the control group. The included studies evaluated therapies such as Atezolizumab (79), Cabozantinib (76), Combined Chemotherapy (58), Demivistat + FOLFIRINOX (266), Durvalumab (3), EGPH20 + GEM-NABP (327), Erlotinib (518), FOLFIRINOX (433), Gemcitabine (2,090), Irinotecan (1,216), Mitazalimab (70), Nab-Paclitaxel (71), Nadunolimab (76), Napabucasin + GEM-NABP (565), Olaparib (124), Narilifox (766), Placebo (322), and Zenocutumab (454). The most significant survival benefit was observed with Irinotecan (OR = 4.96, 95% CI [1.45; 16.91],), while the least survival benefit was seen with Zenocutumab (OR = 0.38, 95% CI [0.03; 4.41],) compared to placebo."

Retrospective data • Novel Coronavirus Disease • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

REACtiVe-2: Phase I evaluation of dendritic cell vaccination and agonistic CD40 therapy following (m)FOLFIRINOX in metastatic pancreatic cancer (ESMO 2025) - P1 | "Conclusions In conclusion, MesoPher/mitazalimab combination therapy is safe and tolerable in patients with metastatic PDAC and enhances systemic immune activation and local immune responses. Future research should evaluate the efficacy of this promising approach with combination strategies as maintenance therapy shortly after completing systemic chemotherapy."

Metastases • P1 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD14 • CD40

REACtiVe-2 Phase 1 data featuring mitazalimab demonstrate immune activation in metastatic pancreatic cancer – to be presented at ESMO 2025 (Alligator Bioscience Press Release) - "The investigator-sponsored trial...demonstrated that the combination of mitazalimab and Amphera’s dendritic cell vaccine MesoPher was safe and well-tolerated, with enhanced systemic and local immune responses. Half of the patients achieved stable disease after three administrations, with post-treatment biopsies revealing increased tumor-infiltrating T cells and reduced collagen deposition."

P1 data • Pancreatic Cancer