NCT07488884
Not yet recruiting
Phase 1
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
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- ImmunityBio, Inc.
- Enrollment
- 30
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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.
- •(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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: 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.
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).
Clinically important changes in laboratory tests and vital signs
Time Frame: 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.
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.
Secondary Outcomes
- 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).)
- Whole Slide Image Availability for Exploratory Image-Outcome Analyses(From baseline diagnostic biopsy (screening) and/or surgical resection up to End-of-Treatment (EOT), assessed up to 104 weeks after first 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.)
- Immune Objective Response Rate (iORR) by iRECIST(From first dose until immune-confirmed progression (iCPD), death, or censoring, with imaging every 8 weeks (±1 week) through 104 weeks after last dose.)
- Immune Duration of Response (iDOR) by iRECIST(From first confirmed iCR or iPR until immune-confirmed progression (iCPD), death, or censoring, with imaging every 8 weeks (±1 week) through 104 weeks after last dose.)
- OS, defined as time from start of study treatment to death resulting from any cause.(From date of first study treatment to death from any cause; participants censored at last known alive date; follow through 104 weeks (2 years) post last dose (or longer if protocol specifies).)
- Major pathologic response, defined as CAP TRG of 0 or 1 at the time of surgical resection.(At time of surgical resection (tissue collected at resection).)
- Biochemical response, defined as > 50% decrease in CA 19-9 from baseline(From baseline (pre-treatment) through the earliest of disease recurrence/progression, start of new anti-cancer therapy, or 104 weeks after last dose; CA 19-9 measured at baseline and on Day 1 of each 28-day treatment cycle.)
- Blood for ctDNA analysis.(From baseline and Day 1 of neoadjuvant Cycles 3 and 5 (each cycle is 28 days), Day 1 of adjuvant Cycle 1 (28-day cycle), and Day 1 of every third adjuvant cycle thereafter, through End-of-Treatment (EOT), assessed up to 104 weeks after last dose.)
Investigators
Similar Trials
Not yet recruiting
Phase 2
Neoadjuvant Immunotherapy ± Radiotherapy in MSI-H/dMMR Locally Advanced Colorectal CancerNCT07403877Fudan University114
Not yet recruiting
Phase 2
Darolutamide ± ADT as Neoadjuvant Therapy in High-Risk/Very High-Risk Localized Prostate CancerNCT07476677Cancer Institute and Hospital, Chinese Academy of Medical Sciences60
Recruiting
Phase 2
Paclitaxel Polymersomes + Carboplatin + Adebelimab: Neoadjuvant Phase Ⅱ Single-Arm Study for Resectable Mucosal MelanomaNCT07336979Sun Yat-sen University32
Recruiting
Phase 1
Neoadjuvant Immunotherapy Combined With Chemotherapy Sequenced With Endoscopic Resection for Esophageal Cancer (Endosurgery-02)NCT07317609Shanghai Zhongshan Hospital60
Not yet recruiting
Not Applicable
QL1706-SOX vs SOX Alone as Neoadjuvant Therapy for Resectable Diffuse-Type Gastric CancerNCT07315035The First Affiliated Hospital with Nanjing Medical University74