Pancreas Cancer, Duct Cell AdenocarcinomaPhase 1NCT07828236
PHASE 1 TRIAL OF Lm-LLO-TT AND GEMCITABINE IN UNRESECTABLE PANCREATIC DUCTAL ADENOCARCINOMA
A Phase 1 study testing Lm-LLO-TT in people with Pancreas Cancer, Duct Cell Adenocarcinoma and Pancreatic Cancer, run by Loki Therapeutics, Inc. at 1 site in United States.
Trial summary
ClinicalTrials.gov Brief Summary This Phase 1, open-label, first-in-human study is designed to evaluate the safety, tolerability, and recommended dose of intraperitoneal (IP) administration of Lm-LLO-TT in combination with low-dose gemcitabine in adults with previously treated, unresectable or metastatic pancreatic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreas Cancer, Duct Cell Adenocarcinoma, Pancreatic Cancer, Advanced Pancreatic Adenocarcinoma
- What is being tested?
- Lm-LLO-TT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2026to 30 Jan 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able and willing to provide written informed consent. Adults aged 18 years or older. Histologically confirmed pancreatic ductal adenocarcinoma (PDAC) with measurable disease per RECIST v1.1.
- Previously treated with at least one line of chemotherapy for metastatic or unresectable disease, including a fluoropyrimidine-based or gemcitabine-based regimen, or have a contraindication to these therapies.
- No radiation therapy, targeted therapy, or chemotherapy within 14 days prior to first study treatment; no immunotherapy or biologic therapy within 28 days prior to first study treatment.
- Recovery to ≤ Grade 2 from clinically significant toxicities of prior therapy. ECOG Performance Status 0-2. Estimated life expectancy greater than 3 months. Adequate organ function, including adequate hematologic, hepatic, and renal function.
- Participants with treated brain metastases may be enrolled if clinically stable for at least 1 month.
- Willing to comply with study procedures and contraceptive requirements. Participants with HIV may be enrolled if receiving antiretroviral therapy and CD4 count is >400 cells/µL.
- Participants with hepatitis B may be enrolled if viral load is undetectable and appropriately treated; participants with hepatitis C may be enrolled following curative treatment.
- Demonstrated tetanus toxoid (TT) immune responsiveness, either at baseline or following administration of a tetanus toxoid booster during screening.
Who cannot join
- History of chronic comorbidities that would significantly limit participation in the study, including severe heart failure (NYHA Class III-IV), end-stage renal disease, substance dependence, or inadequate venous access, as determined by the investigator.
- Candidate for curative-intent surgical resection.
- Surgery within 2 weeks prior to first study treatment.
- Evidence of hepatic cirrhosis or clinically/radiographically significant ascites.
- Blood transfusion within 14 days prior to study treatment or requirement for frequent blood transfusions (>2 per month).
- Treatment with systemically active corticosteroids within 28 days before study treatment (except low-dose dexamethasone ≤2 mg/day or prednisone ≤10 mg/day).
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- Systemic antibiotic therapy within 14 days prior to first dose of Lm-LLO-TT.
- Receipt of another investigational product or vaccine within 28 days prior to first study treatment.
- Receipt of any vaccine other than the protocol-required tetanus toxoid booster within 4 weeks before study treatment or during the initial DLT evaluation period.
- Major surgery, significant traumatic injury, unhealed surgical wounds, or planned surgery requiring general anesthesia within 28 days before study treatment.
- Active, uncontrolled HIV, hepatitis B, hepatitis C, or HTLV-1 infection, or CD4 count <400 cells/µL.
- Presence of implanted prosthetic devices, including orthopedic prostheses, pacemakers, or prosthetic heart valves.
- Chronic immunosuppressive therapy for autoimmune or rheumatologic conditions.
- Pregnant or breastfeeding individuals.
- Active uncontrolled bacterial infection requiring intravenous antibiotics, fever >38.1°C, or unexplained fever within 7 days before Day 1.
- History of Guillain-Barré syndrome within 6 weeks of a previous tetanus toxoid vaccination or prior Arthus-type hypersensitivity reaction to tetanus vaccine.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Einstein College of Medicine/Montefiore Hospital
The Bronx, New York, 10461
About this study
Official title: PHASE 1, OPEN-LABEL, FIRST-IN-HUMAN TRIAL OF INTRAPERITONEA L Lm-LLO-TT AND GEMCITABINE IN PARTICIPANTS WITH UNRESECTABLE PANCREATIC DUCTAL ADENOCARCINOMA
ClinicalTrials.gov Brief Summary
This Phase 1, open-label, first-in-human study is designed to evaluate the safety, tolerability, and recommended dose of intraperitoneal (IP) administration of Lm-LLO-TT in combination with low-dose gemcitabine in adults with previously treated, unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC). Up to 18 participants will be enrolled.
Read more
Lm-LLO-TT is a live attenuated Listeria monocytogenes-based immunotherapy engineered to express a tetanus toxoid antigen. The study will assess the safety of administering Lm-LLO-TT directly into the peritoneal cavity and characterize its use in combination with low-dose gemcitabine.
Eligible participants will receive a tetanus toxoid booster vaccination during screening and undergo placement of an intraperitoneal access port before treatment. Participants will receive a single loading dose of Lm-LLO-TT followed by five cycles of low-dose gemcitabine and low-dose Lm-LLO-TT administered over approximately 17 days. Participants will be monitored for adverse events, laboratory abnormalities, dose-limiting toxicities, and disease outcomes throughout the study.
The primary objective is to assess safety and tolerability and to determine the maximum tolerated dose and recommended dose for future clinical studies. Secondary objectives include evaluation of anti-tumor activity. Exploratory objectives include assessment of immune biomarkers, changes in pancreatic cancer-related symptoms, and changes in pain medication use.
Participants will undergo tumor imaging assessments following treatment and during follow-up. A post-treatment tumor biopsy will be required for the first 10 enrolled participants and optional for subsequent participants. Participants will be followed for safety, disease status, and survival for up to 6 months after treatment initiation.
Read the detailed description
This is a Phase 1, open-label, first-in-human, dose-escalation study designed to evaluate the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of intraperitoneal (IP) administration of Lm-LLO-TT in combination with low-dose gemcitabine in participants with previously treated unresectable or metastatic pancreatic ductal adenocarcinoma (PDAC). Up to 18 participants will be enrolled. The study will use a Bayesian Optimal Interval (BOIN) dose-escalation design to identify the MTD and RP2D of Lm-LLO-TT for future clinical development.
PDAC is associated with poor clinical outcomes and limited treatment options in the advanced disease setting. Lm-LLO-TT is a live attenuated Listeria monocytogenes-based immunotherapy engineered to express a tetanus toxoid (TT) antigen linked to listeriolysin O (LLO). This study will evaluate the safety and biologic activity of administering Lm-LLO-TT directly into the peritoneal cavity in combination with low-dose gemcitabine.
Eligible participants are adults with histologically confirmed PDAC and measurable disease according to RECIST version 1.1 who have received at least one prior systemic treatment regimen for unresectable or metastatic disease or have a contraindication to standard therapies. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, adequate organ function, and a life expectancy greater than 3 months.
During screening, participants will undergo tetanus toxoid immunity testing. All participants will receive a tetanus toxoid booster vaccination before treatment initiation. Tetanus antibody titers will be evaluated before and after the booster vaccination, and evidence of an immune response to tetanus toxoid is required for enrollment. Participants will also undergo placement of an intraperitoneal access port before the first administration of study treatment.
Treatment begins with a single escalating loading dose of Lm-LLO-TT administered intraperitoneally on Day 1. Beginning on Day 2, participants will receive low-dose intraperitoneal gemcitabine followed the next day by low-dose intraperitoneal Lm-LLO-TT. This alternating schedule will be repeated for a total of five gemcitabine/Lm-LLO-TT treatment cycles over approximately 17 days.
The dose-escalation component evaluates escalating loading doses of Lm-LLO-TT while maintaining fixed doses of low-dose gemcitabine and low-dose Lm-LLO-TT. Participants will be enrolled sequentially into dose cohorts, and safety data including dose-limiting toxicities (DLTs) will be reviewed throughout the study. Escalation and de-escalation decisions will follow the protocol-defined BOIN design rules.
The primary objective of the study is to evaluate the safety and tolerability of intraperitoneal Lm-LLO-TT administered in combination with low-dose gemcitabine and to determine the MTD and RP2D. Safety evaluations include adverse event monitoring, physical examinations, vital signs, clinical laboratory assessments, electrocardiograms, and assessment of DLTs.
Secondary objectives include evaluation of preliminary anti-tumor activity. Tumor response will be assessed according to RECIST version 1.1 criteria. Secondary endpoints include objective response rate, disease control rate, and progression-free survival.
Exploratory objectives include assessment of pharmacodynamic and immune biomarkers associated with treatment. Blood samples will be collected for evaluation of circulating biomarkers, including circulating tumor DNA and markers associated with immune responses and tumor microenvironment modulation. Tumor tissue obtained during post-treatment biopsy procedures will be evaluated for immune cell infiltration, tetanus toxoid expression, and other tumor microenvironment biomarkers.
The first 10 enrolled participants will undergo a mandatory post-treatment tumor biopsy approximately 20 to 30 days following completion of treatment. Post-treatment biopsy will be optional for participants enrolled thereafter. Imaging assessments of the chest, abdomen, and pelvis will be performed at approximately Day 20 to 30 following treatment and repeated at approximately 4 and 6 months after treatment initiation.
Additional exploratory assessments will evaluate changes in pancreatic cancer-related symptoms, including pain, nausea, vomiting, and fatigue, as well as changes in concomitant pain medication use among participants who report pain at baseline.
Participants will be monitored for bacterial shedding through urine and fecal sample collection during the treatment and follow-up periods. Participants will also be monitored for safety events of special interest, including infection-related events associated with administration of live attenuated bacterial therapy.
Following completion of treatment, participants will enter a follow-up period that includes safety evaluations, disease assessments, laboratory testing, biomarker assessments, and survival follow-up. Participants will be followed for up to 6 months after initiation of study treatment.
Data generated from this study will be used to characterize the safety profile, determine the recommended dose for future studies, evaluate preliminary anti-tumor activity, and inform the further clinical development of intraperitoneal Lm-LLO-TT in combination with low-dose gemcitabine for the treatment of advanced pancreatic ductal adenocarcinoma.
- Conditions
- Pancreas Cancer, Duct Cell Adenocarcinoma, Pancreatic Cancer, Advanced Pancreatic Adenocarcinoma
- Being tested
- Lm-LLO-TT
- Keywords
- Unresectable Pancreatic Cancer, cancer immunotherapy, Lm-LLO-TT, tetanus toxoid, Listeria, Gemcitabine, Memory T-cells, Listeria monocytogenes Immunotherapy
- Medical subject headings
- Pancreatic Neoplasms, Tetanus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lm-LLO-TTBiological
Lm-LLO-TT is a live attenuated Listeria monocytogenes-based immunotherapy expressing tetanus toxoid and listeriolysin O, developed to stimulate tumor-directed immune responses through activation of tetanus-specific memory T cells.
| Study group | Role | What they receive |
|---|---|---|
| Low dose | Experimental | Low dose Receives: Biological: Lm-LLO-TT |
| High dose | Experimental | Not described Receives: Biological: Lm-LLO-TT |
| Middle dose | Experimental | Middle dose Receives: Biological: Lm-LLO-TT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of intraperitoneal Lm-LLO-TT in combination with low-dose gemcitabine
Measured: Day 1 to Day 45
Secondary outcomes (3)
Objective Response Rate
Percentage of participants with complete response or partial response as assessed by RECIST v1.1.
Measured: Up to 6 months
Disease Control Rate (DCR)
Percentage of participants with complete response, partial response, or stable disease as assessed by RECIST v1.1.
Measured: Day 1 to 6 months
Progression-Free Survival (PFS)
Time from first study treatment to documented disease progression or death.
Measured: Day 1 to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2026
- Study start15 Oct 2026 (estimated)
- Primary completion15 Oct 2028 (estimated)
- Study completion30 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreas Cancer, Duct Cell AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Loki Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07828236
- Sponsor's protocol ID
- LOKI-101-001
- Status last verified
- Sep 2026
- First submitted
- 14 Sep 2026
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) collected during this study, including de-identified participant-level data and supporting study documents, will not be made available to other researchers. The study is an early-phase, first-in-human clinical trial of a proprietary investigational product and no plan currently exists for sharing individual participant data.