Anti-CD38 Antibody With KRAS Vaccine and Anti-PD-1 Antibody in Subjects With Pancreatic Ductal Adenocarcinoma and Refractory Non-Small Cell Lung Cancer

NCT06015724 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00005625
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to test the safety and tolerability of anti-CD38 monoclonal antibody (mAb), daratumumab, in combination with KRAS vaccine (Targovax TG-01/Stimulon QS-21) when given with anti-PD-1 (programmed cell death protein 1) mAb (nivolumab) in patients with advanced non-small cell lung cancer (NSCLC) or pancreatic ductal adenocarcinoma (PDAC). The main questions it aims to answer are:

• How well does daratumumab and nivolumab, when given with a vaccine, control or stop these types of cancer?
• How well does participants bodies handle these study drugs?
• Does this combination of study drugs help participants live longer? Participants will receive daratumumab, nivolumab with KRAS vaccine and have regular tests and procedures to follow how the participants are doing on these study drugs.

Conditions

Pancreatic Ductal Adenocarcinoma; Refractory Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) (Efficacy)

  Evaluation of response by ORR by irRECIST criteria. Response classification will follow the irRECIST criteria and will be defined as PR or CR. Patients who are lost to follow-up without a valid response assessment will be classified as NR (non-responder, progression). The ORR will be computed for all patients with at least one cycle of the study drug.

  every 8 weeks, approximately 2 years

Secondary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  From start of intervention until 30 days following discontinuation of intervention, approximately 2 years

• Progression Free Survival (PFS)

  at 6 months and 9 months

• Duration of Response (DOR)

  approximately 3 years

• Clinical Benefit Rate (CBR)

  approximately 2 years

• Overall Survival

  approximately 3 years

Study Arms (2)

Pancreatic Ductal Adenocarcinoma

EXPERIMENTAL

Drug: Daratumumab; Biological: KRAS vaccine; Drug: Nivolumab

Refractory Non-Small Cell Lung Cancer

EXPERIMENTAL

Drug: Daratumumab; Biological: KRAS vaccine; Drug: Nivolumab

Interventions

Daratumumab DRUG

anti-CD38 monoclonal antibody (mAb)

Also known as: Darzalex Faspro

Pancreatic Ductal Adenocarcinoma; Refractory Non-Small Cell Lung Cancer

KRAS vaccine BIOLOGICAL

Stimulon QS-21 and Targovax TG01

Pancreatic Ductal Adenocarcinoma; Refractory Non-Small Cell Lung Cancer

Nivolumab DRUG

anti-PD-1 (programmed cell death protein 1) monoclonal antibody (mAb)

Also known as: BMS-936558

Pancreatic Ductal Adenocarcinoma; Refractory Non-Small Cell Lung Cancer

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
• Patients with advanced NSCLC, progressing on frontline anti-PD-1/PD-L1 containing therapy (patient with rapid tumor progression will be excluded) and PDAC patients who failed one prior treatment.
• Measurable disease as defined by irRECIST criteria (See Section 7) NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible.
• All patients with mutant KRAS status in either codon 12 (12A, C, D, R, S, V) or 13 (13D) will be included. The status of KRAS and LKB1 will be determined. For patients with KRAS G12C-mutated NSCLC, prior treatment with G12C-targeted therapy will be allowed; a wash-out period of 1 week from the last administration of targeted therapy would be allowed.
• Prior treatment:
• For NSCLC: Anti-PD1/PD-L1 containing therapy; a wash-out period of 4 weeks from the last administration of therapy would be allowed.
• For PDAC: Patients who failed one prior treatment.
• Provide written informed consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willingness to provide mandatory blood specimens for correlative research.
• Willingness to provide mandatory tissue specimens for correlative research.
• ECOG Performance Status (PS) 0, 1 or 2.
• The following laboratory values obtained ≤14 days prior to registration:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1500/mm3

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• Any of the following prior therapies:
• Daratumumab or other anti-CD38 therapies
• Surgery ≤3 weeks prior to registration
• Chemotherapy ≤4 weeks prior to registration
• For NSCLC: anti-PD-1/PD-L1 therapy or second line therapy ≤4 weeks prior to registration; for PDAC: Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways.
• Focal radiation therapy within 14 days prior to first study treatment with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma. Participants must have recovered (ie, Grade ≤1 or at baseline) from radiation-related toxicities prior to first study treatment.
• Treatment with complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease under study within \<2 weeks prior to first study treatment. Such medications are permitted if they are used as supportive care.
• Treatment with any live / attenuated vaccine within 30 days of first study treatment.
• Co-morbid systemic illnesses or other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection

Sponsors & Collaborators

• Georgetown University: lead
• Bristol-Myers Squibb: collaborator
• Janssen, LP: collaborator
• Targovax ASA: collaborator

Study Sites (2)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

daratumumab; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Samir Khleif, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shannon Raue

CONTACT

202-784-5097; sr1657@georgetown.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: August 29, 2023
• Study Start: January 31, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)