Breakthrough Clinical Results
Alligator Bioscience announced the presentation of biomarker data from its OPTIMIZE-1 clinical trial at the 2025 ASCO Annual Meeting. OPTIMIZE-1 is a Phase 1b/2 trial evaluating mitazalimab in combination with mFOLFIRINOX for first-line metastatic pancreatic cancer (mPDAC). The data showed that mitazalimab-induced biomarkers were associated with clinical benefit, including intratumoral immune activation. A fibrosis-related gene signature was identified as potentially predictive of improved overall survival. The observed median overall survival was 14.9 months, and the objective response rate was 54.4%. These results support further development of mitazalimab in mPDAC.
Key Highlights
- Positive biomarker data from the OPTIMIZE-1 trial presented at ASCO 2025.
- Mitazalimab-induced biomarkers associated with clinical benefit in patients with metastatic pancreatic cancer.
- Median overall survival of 14.9 months and objective response rate of 54.4% observed.
- Results support further development of mitazalimab in metastatic pancreatic cancer.
Incidence and Prevalence
Latest Estimates of Incidence and Prevalence of Metastatic Pancreatic Cancer
Epidemiological Data from SEER Database
According to SEER database analyses, significant populations of metastatic pancreatic cancer patients have been documented over different time periods:
- Between 2010-2013, 13,233 patients with stage IV pancreatic cancer with known sites of distant metastases were identified
- A larger SEER analysis identified 57,263 patients diagnosed with metastatic pancreatic cancer (mPDAC) between 1993 and 2013
- A more recent SEER study included 10,527 eligible patients diagnosed with mPDAC from 2010 to 2015
Demographic Information
Demographic data from the 1993-2013 SEER analysis reveals: - 52% of patients were male - Median age was 69 years (range: 15-104)
Survival Statistics
Survival trends for metastatic pancreatic cancer patients show:
- Median overall survival remained stable at 2 months between 1993 and 2013
- The percentage of patients who died within 2 months decreased from 63.5% to 50.6% between 1993 and 2013
- The percentage of patients surviving ≥12 months improved from 4.9% in 1993 to 12.7% in 2013
- The 6-month cumulative incidence of cause-specific mortality was 60.3% and 5.9% for other causes
Metastatic Patterns and Prognostic Factors
- Patients with isolated liver metastases have worse outcomes compared to those with isolated lung or distant nodal metastases
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Predictors of cause-specific mortality for mPDAC include:
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Surgery
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Age
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Tumor size
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Chemotherapy
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Radiation therapy
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Bone metastasis
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Liver metastasis
Genetic Characteristics
- BRCA1/2 mutations occur in approximately 5% of the general Caucasian population with metastatic pancreatic cancer
- MSI-H (high microsatellite instability) occurs in approximately 1% of metastatic pancreatic cancers
These statistics provide insight into the documented cases of metastatic pancreatic cancer from the SEER database analyses, though comprehensive global incidence and prevalence figures specific to metastatic pancreatic cancer are not available in the provided context.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Metastatic Pancreatic Cancer
Standard of Care Evolution
NALIRIFOX (liposomal irinotecan, fluorouracil, leucovorin, oxaliplatin) is emerging as a standard of care in the metastatic setting for pancreatic ductal adenocarcinoma (PDAC).
Targeted Therapies
Targeted therapies represent a significant emerging approach:
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PARP inhibitors: Olaparib has received regulatory approval for maintenance therapy in BRCA-mutated mPDAC. These inhibitors improve progression-free survival when used as maintenance treatment in patients with BRCA1/-2 germline mutations after platinum-based chemotherapy. These mutations occur in approximately 5% of the general Caucasian population with mPDAC.
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KRAS-targeted treatments: These address mutations present in 80% of pancreatic cancer cases.
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Other targeted agents include mTOR inhibitor everolimus, pembrolizumab, palbociclib, nintedanib, cetuximab, crizotinib, tamoxifen, and combinations of lapatinib and trastuzumab.
Immunotherapy Approaches
Several immunotherapeutic strategies are being investigated:
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Immune checkpoint inhibitors like PD1/PD-L1 monoclonal antibodies show particular effectiveness in tumors with high microsatellite instability (MSI-h), though only a portion of the small subgroup of MSI-H mPDACs (frequency about 1%) benefits substantially from this treatment.
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In a case study, a combination of chemotherapy (S-1) and sintilimab demonstrated significant response in a patient with SMAD4 and TSC2 mutations.
Tumor Microenvironment Targeting
Novel approaches focusing on tumor microenvironment include:
- PEGylated rHuPH20, a recombinant human hyaluronidase that targets hyaluronic acid in the tumor microenvironment. Hyaluronic acid increases interstitial tumor pressure, limiting access of effective anticancer drugs.
Metabolic Approaches
- Oral recombinant methioninase (o-rMETase) combined with FOLFIRINOX and a low-methionine diet has shown promising results in a case report of stage IV pancreatic cancer.
Precision Medicine
Precision medicine approaches using next-generation sequencing are helping identify molecular targets for therapies focusing on:
- DNA damage repair deficiency
- Gene fusions (such as TBL1XR1-PIK3CA and EIF3E-RSPO2)
- Novel immune therapy approaches
- Tumor microenvironment strategies
- Synthetic lethality strategies
These emerging mechanisms of action represent the cutting edge of research in metastatic pancreatic cancer treatment, offering new hope for improved outcomes in this challenging disease.
Study Design Parameters
Key Trials for Metastatic Pancreatic Cancer: Study Design Parameters and Endpoints
PANTHEIA-SEOM Study
- Design: Multicentric (16 Spanish hospitals), observational, longitudinal, non-interventional study
- Population: Patients with pathologically confirmed metastatic pancreatic adenocarcinoma (2020-2023)
- Endpoints: Association between overall survival (OS), Systemic Inflammation Response Index (SIRI), and weight loss
- Key findings: Higher SIRI (≥2.3 × 10/L) correlated with decreased survival (4 vs 18 months) and was associated with weight loss
Eribulin Phase II Study
- Design: Single arm phase II trial using a Simon 2-stage design
- Population: Advanced pancreatic cancer patients previously treated with gemcitabine
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Endpoints:
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Primary: response rate
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Secondary: time to progression and overall survival
- Key findings: No objective responses; median time to progression was 1.4 months; median OS was 6.1 months
AGS-1C4D4 with Gemcitabine Trial
- Design: Randomized, phase II study (1:2 randomization)
- Population: Previously untreated, metastatic pancreatic adenocarcinoma with ECOG 0/1
- Primary endpoint: 6-month survival rate
- Treatment: Gemcitabine alone vs. gemcitabine plus AGS-1C4D4
- Results: 6-month survival was 44.4% in gemcitabine arm vs. 60.9% in combination arm (p=0.03)
Cetuximab plus Gemcitabine/Oxaliplatin Study
- Design: Phase II trial
- Population: Metastatic pancreatic adenocarcinoma
- Primary endpoint: Response according to RECIST
- Results: 33% overall response rate, median time to progression of 118 days, median OS of 213 days
Gemcitabine-Erlotinib plus Bevacizumab Trial
- Design: Double-blind, phase III trial
- Population: Metastatic pancreatic adenocarcinoma (301 patients in placebo group, 306 in bevacizumab group)
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Endpoints:
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Primary: OS
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Secondary: PFS, disease control rate, and safety
- Results: No statistically significant improvement in OS (7.1 vs 6.0 months); significant PFS improvement with bevacizumab
Sorafenib with Chemotherapy Trial
- Design: Phase II randomized trial (1:1 ratio)
- Population: Locally advanced or metastatic pancreatic adenocarcinoma
- Treatment: Cisplatin plus gemcitabine with or without sorafenib
- Results: No significant improvement with sorafenib (median PFS: 4.3 vs 4.5 months; median OS: 7.5 vs 8.3 months)
FOLFIRINOX Trials
- Noted as effective in selected patients with good performance status (ECOG 0-1)
- Associated with more toxicities but significant increased survival compared to gemcitabine alone
Drug used in other indications
Based on the provided context, there is no information available about mitazalimab and mFOLFIRINOX being trialled for indications other than metastatic pancreatic cancer. The context does not specifically mention mitazalimab at all, and while there are references to FOLFIRINOX (not mFOLFIRINOX), these are only in relation to pancreatic cancer treatment.
Additionally, there is no information provided about intervention models for trials with mitazalimab and mFOLFIRINOX for any indications.
The context does mention other treatments being studied for pancreatic cancer, including: - Afatinib with gemcitabine/nab-paclitaxel - Trametinib with hydroxychloroquine or CDK4/6 inhibitors - CPI-613 alone and with Gemcitabine - Bevacizumab with gemcitabine - Various targeted therapies based on molecular profiling
However, these are not related to the specific query about mitazalimab and mFOLFIRINOX trials for indications other than metastatic pancreatic cancer.