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

Brief summary public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: Daratumumab. anti-CD38 monoclonal antibody (mAb)

Intervention public domain (ClinicalTrials.gov)

Biological: KRAS vaccine. Stimulon QS-21 and Targovax TG01

Intervention public domain (ClinicalTrials.gov)

Drug: Nivolumab. anti-PD-1 (programmed cell death protein 1) monoclonal antibody (mAb)

Arm public domain (ClinicalTrials.gov)

Pancreatic Ductal Adenocarcinoma (experimental):

Arm public domain (ClinicalTrials.gov)

Refractory Non-Small Cell Lung Cancer (experimental):

Primary outcome public domain (ClinicalTrials.gov)

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. Time frame: every 8 weeks, approximately 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]. Time frame: From start of intervention until 30 days following discontinuation of intervention, approximately 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS). Time frame: at 6 months and 9 months.

Secondary outcome public domain (ClinicalTrials.gov)

Duration of Response (DOR). Time frame: approximately 3 years.

Secondary outcome public domain (ClinicalTrials.gov)

Clinical Benefit Rate (CBR). Time frame: approximately 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Overall Survival. Time frame: approximately 3 years.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: 1. Age ≥18 years 2. 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. 3. 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. 4. 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. 5. 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. 6. Provide written informed consent. 7. Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study). 8. Willingness to provide blood specimens for correlative research. 9. Willingness to provide tissue specimens for correlative research (when available/feasible). 10. ECOG Performance Status (PS) 0, 1 or 2. 11. The following laboratory values obtained ≤14 days prior to registration: * Hemoglobin ≥9.0 g/dL * Absolute neutrophil count (ANC) ≥1500/mm3 * Platelet count ≥100,000/mm3 * Total bilirubin ≤1.5 x ULN (upper limit of normal) * ALT and AST ≤3 x ULN (≤5 x ULN for patients with liver involvement) * PT (prothrombin time)/INR/aPTT (activated partial thromboplastin time) ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy * Calculated creatinine clearance (CrCl) ≥20 mL/min using the Cockcroft-Gault formula 12. Negative pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only. Exclusion Criteria: 1. 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 2. Any of the following prior therapies: * Daratumumab or other anti-CD38 therapies * Surgery ≤3 weeks prior to …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 19 participants (actual).