Open-Label, Phase 1 Clinical Trial of Neoadjuvant Nogapendekin Alfa Inbakicept, Sotevtamab, and Zabadinostat in Combination With Gemcitabine and Nab-Paclitaxel for Participants With Borderline Resectable or Locally Advanced Pancreatic Cancer

NCT07488884 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: ResQ108B-PANC
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, phase 1 clinical trial to evaluate the safety and preliminary efficacy of neoadjuvant chemoimmunotherapy (NAI, sotevtamab, and zabadinostat in combination with gemcitabine and nab-paclitaxel) followed by resection and adjuvant immunotherapy for participants with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC). Eligible participants will undergo endoscopic ultrasound (EUS)-guided biopsies of the primary pancreatic tumor within 7 days of enrollment and prior to study day 1. EUS-guided biopsies will be used for histopathological examination to give clinical diagnostic information (as SoC) and will be stored in an ethically approved tissue bank.

Conditions

Pancreatic Cancer Resectable; Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Number of participants experiencing ≥1 treatment-emergent adverse event (TEAE) and ≥1 serious adverse event (SAE), graded per NCI CTCAE v5.0. Adverse events will be coded using MedDRA. Analyses will be performed in the safety population (all participants receiving ≥1 dose of study treatment).

  From first dose through 30 days after last dose (SAEs and immune-related AEs followed for 90 days after last dose); survival/safety follow-up through 104 weeks (2 years) post last dose.

• Clinically important changes in laboratory tests and vital signs

  Number and percent of participants with protocol-defined clinically important laboratory abnormalities (hematology, chemistry including liver/renal, coagulation) or vital-sign changes that meet action criteria or result in dose modification, treatment interruption, or discontinuation; summarized by grade and action taken.

  Baseline (pre-dose) through 30 days after last dose (clinically important labs/vitals and related actions); SAE/irAE follow-up 90 days; long-term follow-up through 104 weeks (2 years) post last dose.

Secondary Outcomes (12)

• RFS, defined as time from surgical resection to disease recurrence or death from any cause, whichever occurs first, by RECIST v1.1.

  From date of surgical resection until documented disease recurrence or death from any cause, whichever occurs first; participants censored at last disease assessment or at 104 weeks (2 years) post last dose.

• R0 resection rate, defined as the percentage of cases having a pathologically complete resection with a negative resection margin.

  At time of surgical resection (performed within 8 months of first study dose).

• ORR by RECIST v1.1

  From first study treatment until documented objective response or censoring; tumor assessments every 8 weeks (±1 week) through last treatment dose and per follow-up schedule through 104 weeks.

• DOR by RECIST v1.1.

  For responders, from date of first documented CR/PR to date of documented progression or death (any cause); follow until event or censoring through 104 weeks.

• Immune Recurrence-Free Survival (iRFS) by iRECIST

  From date of surgical resection until immune-confirmed progression (iCPD), death, or censoring, with imaging every 8 weeks (±1 week) through 104 weeks after last dose.

Study Arms (1)

Neoadjuvant NAI + sotevtamab + zabadinostat + gemcitabine/nab-paclitaxel; adjuvant NAI

EXPERIMENTAL

Participants receive neoadjuvant therapy of nogapendekin alfa inbakicept (NAI) SC + sotevtamab IV + oral zabadinostat plus gemcitabine and nab-paclitaxel IV for up to 6 × 28-day cycles, with zabadinostat given Days 1-5 (second course Days 15-19 per SRC), sotevtamab/gemcitabine/nab-paclitaxel on Days 1, 8, 15, and NAI on Days 1 and 15 (weight-based ≤50 kg). After ≥2 cycles participants may be reassessed for surgical resection; resected participants receive adjuvant NAI SC on Days 1 and 15 of each 28-day cycle until recurrence, unacceptable toxicity, withdrawal, or investigator decision. Premedication and infusion-reaction management per protocol; safety follow-up per study schedule.

Drug: Nogapendekin Alfa Inbakicept (N803); Drug: Sotevtamab; Drug: Zabadinostat (CXD101); Drug: Nab paclitaxel / gemcitabine

Interventions

Nogapendekin Alfa Inbakicept (N803) DRUG

1.2mg SC

Also known as: N-803, ANKTIVA

Neoadjuvant NAI + sotevtamab + zabadinostat + gemcitabine/nab-paclitaxel; adjuvant NAI

Sotevtamab DRUG

800mg IV

Neoadjuvant NAI + sotevtamab + zabadinostat + gemcitabine/nab-paclitaxel; adjuvant NAI

Zabadinostat (CXD101) DRUG

10mg IV

Neoadjuvant NAI + sotevtamab + zabadinostat + gemcitabine/nab-paclitaxel; adjuvant NAI

Nab paclitaxel / gemcitabine DRUG

Nab-Paclitaxel (125mg/m2 IV) and Gemcitabine (1,000 mg/m2 IV)

Neoadjuvant NAI + sotevtamab + zabadinostat + gemcitabine/nab-paclitaxel; adjuvant NAI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Histologically or cytologically confirmed PDAC that is confined to the pancreas.
• Borderline resectable (surgical resection possible but challenging) or locally advanced (surgical resection not possible) PDAC, as determined by the local investigator based onlocal institutional guidelines.
• Measurable tumor lesions according to RECIST v1.1. (within 90 days prior to first dose of study treatment).
• Have not received prior anticancer therapy for pancreatic cancer.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males. Female participants of child-bearing potential must agree to use effective contraception for up to 7 months after completion of therapy, and nonsterile male participants must agree to use a condom for up to 7 months after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables, 2 forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.

You may not qualify if:

• Resectable PDAC, meeting the following criteria upon CT/MRI: (a)No superior mesenteric vein (SMV) or portal vein (PV) distortion; (b) Clear fat planes around superior mesenteric artery (SMA), celiac artery (CA), and common hepatic artery (CHA).
• Participants for whom an operation is not considered in the participant's best interest (eg, due to comorbidity).
• Histologically or cytologically confirmed pancreatic tumor that is not adenocarcinoma.
• CA19-9 \> 1,000 U/mL.
• QTc interval using Fridericia's formula (QTcF) \> 470 ms.
• If participants have had major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.
• Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Inadequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to baseline: (a) Absolute neutrophil count (ANC) \< 1,500 cells/μL without granulocyte colonystimulating factor support, (b) Lymphocyte count \< 500/μL, (c) platelet count \< 100,000/μL without transfusion (d) Hemoglobin \< 8.0 g/dL Note: Participants may be transfused to meet this criterion, (e) International Normalized Ratio (INR) or aPTT activated partial thromboplastin time (aPTT) \< 1.5 × upper limit of normal (ULN) Note: This applies only to participants who are not receiving therapeutic anticoagulation; participants receiving therapeutic anticoagulation should be on a stable dose. (f) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase \> 2.5 × ULN, with the following exception: Participants with documented liver metastases: AST and/or ALT \> 5 × ULN. (g) Serum bilirubin ≤ 3 × ULN (h) Creatinine clearance ≤ 60 mL/min (calculated using the Cockcroft-Gault formula), (i) Serum albumin ≤ 3.0 g/dL. (j) Urine dipstick for proteinuria \> 2+ (within 7 days prior to initiation of study treatment). Participants with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours.
• Significant cardiovascular disease (such as New York Heart Association cardiac disease class II or greater), myocardial infarction within 3 months prior to baseline, unstable arrhythmias, or unstable angina.
• Severe infections at the time of enrollment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Participants receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Prior allogeneic bone marrow transplantation or solid organ transplant.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

ALT-803; Taxes; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: March 23, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 29, 2026

Record last verified: 2026-03