Trial Title:
Anti-CD38 Antibody With KRAS Vaccine and Anti-PD-1 Antibody in Subjects With Pancreatic Ductal Adenocarcinoma and Refractory Non-Small Cell Lung Cancer
NCT ID:
NCT06015724
Condition:
Pancreatic Ductal Adenocarcinoma
Refractory Non-Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Nivolumab
Daratumumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Daratumumab
Description:
anti-CD38 monoclonal antibody (mAb)
Arm group label:
Pancreatic Ductal Adenocarcinoma
Arm group label:
Refractory Non-Small Cell Lung Cancer
Other name:
Darzalex Faspro
Intervention type:
Biological
Intervention name:
KRAS vaccine
Description:
Stimulon QS-21 and Targovax TG01
Arm group label:
Pancreatic Ductal Adenocarcinoma
Arm group label:
Refractory Non-Small Cell Lung Cancer
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
anti-PD-1 (programmed cell death protein 1) monoclonal antibody (mAb)
Arm group label:
Pancreatic Ductal Adenocarcinoma
Arm group label:
Refractory Non-Small Cell Lung Cancer
Other name:
BMS-936558
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.
Criteria for eligibility:
Criteria:
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. Patients with known actionable driver alterations such as EGFR, ALK, ROS1, BRAF,
NTRK1/2/3, METex14, RET, ERBB2 (HER2) and concurrent KRAS mutations will be reviewed
on a case-by-case basis and patients must have experienced progression on
appropriate first-line targeted therapy and anti-PD-1/PD-L1 as indicated.
6. 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.
7. Provide written informed consent.
8. Willing to return to enrolling institution for follow-up (during the Active
Monitoring Phase of the study).
9. Ability to complete questionnaire(s) by themselves or with assistance.
10. Willingness to provide mandatory blood specimens for correlative research.
11. Willingness to provide mandatory tissue specimens for correlative research.
12. ECOG Performance Status (PS) 0, 1 or 2.
13. 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
14. 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 registration
- Chemotherapy ≤4 weeks prior to registration
- For NSCLC: anti-PD-1/PD-L1 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.
3. 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.
4. Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection
• Symptomatic CHF (class II and above that are not properly controlled on
maintenance therapy or that have been hospitalized in the last 4 weeks for heart
failure)
• Unstable angina pectoris
• Cardiac arrhythmia
- Or psychiatric illness/social situations that would limit compliance with study
requirements.
5. Receiving any other investigational agent, which would be considered as a treatment
for the primary neoplasm.
6. Other active malignancy ≤5 years prior to registration. EXCEPTIONS: Squamous and
basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or
other non-invasive lesions that in the opinion of the investigator, with concurrence
with the sponsor's medical monitor, is considered cured with minimal risk of
recurrence within 3 years.
7. History of myocardial infarction ≤6 months, or CHF (class II and above that are not
properly controlled on maintenance therapy or that have been hospitalized in the
last 4 weeks for heart failure) requiring use of ongoing maintenance therapy for
life-threatening ventricular arrhythmias.
8. Patients with known primary CNS malignancy or symptomatic CNS metastases are
excluded, with the following exceptions:
- Patients with asymptomatic untreated CNS disease may be enrolled, provided all
of the following criteria are met:
o Evaluable or measurable disease outside the CNS
o No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within
10 mm of the optic apparatus (optic nerves and chiasm)
- No history of intracranial hemorrhage or spinal cord hemorrhage
- No ongoing requirement for dexamethasone for CNS disease; patients on a
stable dose of anticonvulsants are permitted.
- No neurosurgical resection or brain biopsy ≤28 days prior to registration
- Patients with asymptomatic treated CNS metastases may be enrolled, provided all
the criteria listed above are met as well as the following:
- Radiographic demonstration of improvement upon the completion of
CNS-directed therapy and no evidence of interim progression between the
completion of CNS-directed therapy and the screening radiographic study
- No stereotactic radiation or whole-brain radiation ≤28 days prior to
registration
- Screening CNS radiographic study ≥4 weeks from completion of radiotherapy
and ≥ 2 weeks from discontinuation of corticosteroids
9. a. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins or vaccines.
9. b. Patients with a plan to receive yellow fever or other live (attenuated) vaccines
during the course of study.
9. c. Patients who have a history or current evidence of bleeding disorder, i.e., any
hemorrhage/bleeding event of CTCAE Grade ≥2, ≤28 days prior to registration.
9. d. Patients on supraphysiologic doses of steroids or use of such ≤ 6weeks prior to
registration.
9. e. Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
9. f. History or risk of autoimmune disease, including, but not limited to, systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular
thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis,
Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis,
autoimmune thyroid disease, vasculitis, or glomerulonephritis. Note: Patients with a
history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone
are eligible. Patients with controlled Type 1 diabetes mellitus (T1DM) on a stable
insulin regimen are eligible. Patients with eczema, psoriasis, lichen simplex
chronicus of vitiligo with dermatologic manifestations only (e.g., patients with
psoriatic arthritis would be excluded) are permitted provided that they meet the
following conditions:
o Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular
manifestations
- Rash must cover less than 10% of body surface area (BSA)
- Disease is well controlled at baseline and only requiring low potency topical
steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone
0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
- No acute exacerbations of underlying condition within the last 12 months (not
requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids,
biologic agents, oral calcineurin inhibitors; high potency or oral steroids).
9. g. History of idiopathic pulmonary fibrosis, pneumonitis (including drug
induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia, etc.), or evidence of active pneumonitis on screening
chest CT scan. Note: History of radiation pneumonitis in the radiation field
(fibrosis) is permitted.
9. h. Any infection > Grade 2 ≤4 weeks prior to registration, including, but not
limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia.
9. i. History of peripheral neuropathy ≥Grade 2.
10. Subject is Seropositive for HIV. Seropositive for hepatitis B (defined by a
positive test for HBsAg). Subjects with resolved infection (i.e., subjects who
are HBsAg negative but positive for anti-HBc and/or anti-HBs) must be screened
using RT-PCR measurement of HBV DNA levels. Those who are PCR positive will be
excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV
vaccination (anti-HBs positivity as the only serologic marker) AND a known
history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
Seropositive for hepatitis C (except in the setting of a SVR, defined as
aviremia at least 12 weeks after completion of antiviral therapy).
11. COPD with a FEV1 < 50% of predicted normal. Note that FEV1 testing is required
for participants suspected of having COPD and participants must be excluded if
FEV1 is < 50% of predicted normal.
12. Moderate or severe persistent asthma within the past 2 years, or uncontrolled
asthma of any classification. Note that participants who currently have
controlled intermittent asthma or controlled mild persistent asthma are allowed
to participate.
13. Prisoners or subjects who are compulsory detained.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Georgetown Lombardi Comprehensive Cancer Center
Address:
City:
Washington
Zip:
20007
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jennifer Mont
Phone:
202-687-8974
Email:
jem257@georgetown.edu
Contact backup:
Last name:
Christina Benedict
Email:
cnb54@georgetown.edu
Investigator:
Last name:
Benjamin Weinberg, MD
Email:
Sub-Investigator
Investigator:
Last name:
Joshua Reuss, MD
Email:
Sub-Investigator
Investigator:
Last name:
Samin N. Khleif, MD
Email:
Principal Investigator
Start date:
January 31, 2024
Completion date:
January 2026
Lead sponsor:
Agency:
Georgetown University
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
Collaborator:
Agency:
Janssen, LP
Agency class:
Industry
Collaborator:
Agency:
Targovax ASA
Agency class:
Industry
Source:
Georgetown University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06015724
