A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF for the Treatment of Advanced Stage Adenocarcinoma

• ClinicalTrials.gov Identifier: NCT05101356
• Recruitment Status: Recruiting
• First Posted: November 1, 2021
• Last Update Posted: November 8, 2021
• Sponsor: Tianhong Li
• Collaborators: National Cancer Institute (NCI); LabyRx Immunologic Therapeutics
• Information provided by (Responsible Party): Tianhong Li, University of California, Davis

Study Description

Brief Summary:

This phase I trial tests the safety and side effects of a cancer vaccine called Labvax 3(22)-23 and GM-CSF in treating adenocarcinoma that has spread to other places in the body (advanced stage). Labvax 3(22)-23 is designed to target a specific antigen (labyrinthin), which is a protein found on the surface of adenocarcinoma tumor cells. Labyrinthin is a protein that is not expressed on normal cells in the skin, lungs, salivary glands, pancreas, nor other tissues. In adenocarcinoma, the tumor cells produce too much labyrinthin causing them to express this protein on the surface of the tumor cells. One way to control the growth of these tumor cells is to teach the immune system to generate an immune response against the labyrinthin protein by vaccination against labyrinthin. GM-CSF, or sargramostim, is a protein that acts as a white blood cell growth factor. It has also been shown to stimulate immune system. Thus, administration of GM-CSF may help to boost the immune system response when given together with the vaccine. This study may improve the general knowledge about Labvax 3(22)-23 and how the body may generate an immune response to kill adenocarcinoma tumor cells.

Condition or disease	Intervention/treatment	Phase
Advanced Adenocarcinoma; Advanced Malignant Solid Neoplasm; Metastatic Adenocarcinoma; Metastatic Malignant Solid Neoplasm; Recurrent Adenocarcinoma; Recurrent Malignant Solid Neoplasm	Biological: Antineoplastic Vaccine; Biological: Sargramostim	Phase 1

Detailed Description:

PRIMARY OBJECTIVE: To evaluate the adverse events of LabVax 3(22)-23 in subjects with advanced/metastatic or recurrent adenocarcinoma.

SECONDARY OBJECTIVE: To obtain the preliminary assessment on the efficacy of LabVax 3(22)-23 and adjuvant sargramostim (GM-CSF) by Response Evaluation Criteria in Solid Tumors (RECIST)

OUTLINE: Patients receive sargramostim subcutaneously (SC) and LabVax 3(22)-23 intradermally (ID) on weeks 1, 2, 4, 8, and 12 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Open Label Study of Labvax 3(22)-23 and Adjuvant GM-CSF in Subjects With Advanced Stage Adenocarcinoma
• Actual Study Start Date: October 13, 2021
• Estimated Primary Completion Date: September 20, 2023
• Estimated Study Completion Date: September 20, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment (sargramostim, LabVax 3(22)-23); Patients receive sargramostim SC and LabVax 3(22)-23 ID on weeks 1, 2, 4, 8, and 12 in the absence of disease progression or unacceptable toxicity.	Biological: Antineoplastic Vaccine; Given LabVax 3(22)-23 ID; Other Names: cancer treatment vaccine; Cancer Vaccine; Neoplasm Vaccine; Tumor Vaccine; Biological: Sargramostim; Given SC; Other Names: 23-L-Leucinecolony-Stimulating Factor 2; DRG-0012; Leukine; Prokine; rhu GM-CFS; Sagramostim; Sargramostatin

Outcome Measures

Primary Outcome Measures :

1. Dose-limiting toxicities (DLT) [ Time Frame: Up to 30 days after the last vaccination ]
   Will be assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (V)5.0. The type, grade, frequency and proportion of toxicities noted during the treatment period will be reported, along with associated 95% two-sided exact confidence interval of proportion. All adverse events noted by the investigator will be tabulated according to the affected body system.

Secondary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: Up to 1 year ]
   Will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V)1.1 guidelines. The fractions will be reported along with 95% two-sided exact confidence intervals. Comparisons between arms will be performed by Fisher's Exact tests. Investigators will also characterize the proportion who remain that either respond or have stable disease, compared to those who progress.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Ability to understand and willingness to sign an informed consent form
• Subjects of at least 18 years of age with histologically confirmed diagnosis of adenocarcinoma
• Subjects with advanced/metastatic or recurrent solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 are eligible for participation
• Subjects can either have had no response to or progressed on prior cancer therapy. Patients must have recovered from all clinically significant treatment-related toxicities to grade 1 or less
• No limit on prior lines of therapy for metastatic disease. Prior chemotherapy, immunotherapy or molecularly targeted therapy must have been completed for at least 3 weeks prior to 1st vaccine injection. Prior palliative radiation must have been completed for at least 2 weeks prior to 1st vaccine injection
• Subjects with known untreated, active brain and/or leptomeningeal metastases are excluded. Subjects with treated brain metastasis who are neurologically stable and off steroids for at least one week is eligible
• Subjects must have documentation of positive delayed-type hypersensitivity (DTH) response to common recall antigens prior to 1st vaccine injection. As part of the prescreen evaluation, subjects will undergo DTH testing to at least one common recall antigen; selection will be at the discretion of the physician, based upon the history and physical (mumps, Trichophyton, Candida antigens, influenza [flu] matrix, and/or purified protein derivative [PPD], etc.). Skin tests will be read at or about 48 hours. A skin reaction will be considered positive if there is any measurable induration associated with erythema of 10 mm or greater. Erythema alone will not be regarded as a positive DTH response
• All subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• All subjects must have a life expectancy of >= 6 months at the time of 1st vaccine injection
• All laboratory testing and all radiologic tests (e.g., computed tomography [CT], positron emission tomography [PET] or magnetic resonance imaging [MRI] scan) must be done within 4 weeks prior to 1st vaccine injection
• Absolute granulocyte count (AGC) >= 1,000 obtained within 4 weeks prior to 1st vaccine injection
• Pre-treatment platelet count of >= 75,000 obtained within 4 weeks prior to 1st vaccine injection
• A pre-treatment serum creatinine of =< 1.5 mg/dL is required. Measurements must be obtained within 4 weeks prior to 1st vaccine injection
• Serum bilirubin =< 1.5 obtained within 4 weeks prior to 1st vaccine injection
• Aspartate aminotransferase (AST) =< 2.5 x institutional upper limits of normal (=< 5x if with liver metastases) obtained within 4 weeks prior to 1st vaccine injection
• Because the effects of the vaccine on the unborn fetus or nursing infant are unknown, pregnant and nursing women are ineligible. Women of childbearing age must have a negative urine or serum pregnancy test (human chorionic gonadotropin [HCG]). Subjects must agree to follow strict contraceptive practices during the course of this trial

Exclusion Criteria:

• Known active immunological disease, autoimmune disease, hereditary or congenital immunodeficiencies, underlying immunodeficiency, or altered immune function (e.g., active Grave's disease, acquired immunodeficiency virus [AIDS]/human immunodeficiency virus [HIV], Addison's disease, myasthenia gravis, severe atopic dermatitis, rheumatoid arthritis, eczema scleroderma, Goodpasture's syndrome, Sjogren's syndrome, ankylosing spondylitis, Hashimoto's thyroiditis, systemic lupus erythematosus, autoimmune neutropenia/thrombocytopenia, immune-mediated hemolytic anemia, or previous history of anaphylaxis requiring intensive care unit [ICU] care)
• Subjects who have had a prior splenectomy are ineligible
• Pregnant or nursing women
• Any medical condition including additional malignancies, laboratory abnormalities, or psychiatric illness that in the opinion of the investigator would prevent the subject from participating and adhering to study related procedures
• Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the subject's safety or compliance on trial
• Severe infection that in the opinion of the investigator would interfere with subject safety or compliance on trial within 4 weeks prior to enrollment
• Subjects who have contraindications to GM-CSF injections according to the package insert (e.g., subjects with excessive leukemic myeloid blasts in the bone marrow or peripheral blood [>= 10%]; known hypersensitivity to GM-CSF, yeast-derived products or any component of the product)

Contacts and Locations

Locations

United States, California

University of California Davis Comprehensive Cancer Center; Recruiting

Sacramento, California, United States, 95817

Contact: Tianhong Li 916-734-3604 thli@ucdavis.edu

Principal Investigator: Tianhong Li

Sponsors and Collaborators

Tianhong Li

National Cancer Institute (NCI)

LabyRx Immunologic Therapeutics

Investigators

• Principal Investigator: Tianhong Li; University of California, Davis

More Information

• Responsible Party: Tianhong Li, Principal Investigator, University of California, Davis
• ClinicalTrials.gov Identifier: NCT05101356
• Other Study ID Numbers: UCDCC#296; NCI-2021-10667 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); UCDCC#296 ( Other Identifier: University of California Davis Comprehensive Cancer Center ); P30CA093373 ( U.S. NIH Grant/Contract )
• First Posted: November 1, 2021
• Last Update Posted: November 8, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Neoplasms; Adenocarcinoma; Recurrence; Disease Attributes; Pathologic Processes; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Antineoplastic Agents; Vaccines; Sargramostim; Immunologic Factors; Physiological Effects of Drugs