A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone or in Combination With Pembrolizumab for the Treatment of Advanced Stage Adenocarcinoma

NCT05101356 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UCDCC#296NCI-2021-10667P30CA093373
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1/2 trial tests the safety and effectiveness of a cancer vaccine called Labvax 3(22)-23 and GM-CSF alone or in combination with pembrolizumab 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. In the second phase of the study, participants will also receive pembrolizumab, which may improve anti-cancer activity when given with Labvax 3(22)-23 and GM-CSF.

Conditions

Advanced Adenocarcinoma; Advanced Malignant Solid Neoplasm; Metastatic Adenocarcinoma; Metastatic Malignant Solid Neoplasm; Recurrent Adenocarcinoma; Recurrent Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (3)

• Phase 1: Dose-limiting toxicities (DLT)

  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.

  First LabVax 3(22)-23 injection through 14 days following the second LabVax 3(22)-23 injection

• Phase 1: Adverse events (AEs)

  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.

  Up to 30 days after the last dose of study treatment

• Phase 2: Objective response rate (ORR)

  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.

  Up to 12 months after last dose of study treatment

Secondary Outcomes (5)

• Phase 1: Objective response rate (ORR)

  Up to 12 months after last dose of study treatment

• Phase 2: Dose-limiting toxicities (DLT)

  Up to 30 days after the last LabVax 3(22)-23 vaccination

• Phase 2: Adverse events (AEs)

  Up to 30 days after the last dose of study treatment

• Phase 2: Progression free survival (PFS)

  Up to 12 months after last dose of study treatment

• Phase 2: Overall survival (OS)

  Up to 12 months after last dose of study treatment

Study Arms (2)

Phase 1 Treatment (sargramostim, LabVax 3(22)-23)

EXPERIMENTAL

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; Biological: Sargramostim

Phase 2 Treatment (sargramostim, LabVax 3(22)-23, pembrolizumab)

EXPERIMENTAL

Pembrolizumab will be given intravenously every 3 weeks for up to 12 cycles on Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, and 34. Participants will be given LabVax 3(22)-23 (intradermally) and adjuvant GM-CSF (subcutaneously) on weeks 7, 8, 10, 14, and 18.

Biological: Antineoplastic Vaccine; Biological: Sargramostim; Biological: Pembrolizumab

Interventions

Antineoplastic Vaccine BIOLOGICAL

Given LabVax 3(22)-23 ID

Also known as: cancer treatment vaccine, Cancer Vaccine, Neoplasm Vaccine, Tumor Vaccine

Phase 1 Treatment (sargramostim, LabVax 3(22)-23); Phase 2 Treatment (sargramostim, LabVax 3(22)-23, pembrolizumab)

Sargramostim BIOLOGICAL

Given SC

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

Phase 1 Treatment (sargramostim, LabVax 3(22)-23); Phase 2 Treatment (sargramostim, LabVax 3(22)-23, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV per standard of care

Also known as: KEYTRUDA, MK-3475

Phase 2 Treatment (sargramostim, LabVax 3(22)-23, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• For Phase 2, Cohort A, participants must have:
• Histologically confirmed diagnosis of labyrinthin-positive lung adenocarcinoma.
• Received at least one line of anti-PD-1 or anti-PD-L1 therapy for any stage of NSCLC. Anti-PD-1 or anti-PD-L1 may have been given alone or in combination with other therapy.
• Progressed on at least one line of therapy if participant has a known sensitizing mutation for which an FDA-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, and MET sensitizing mutations).
• For Phase 2, all subjects must be candidates for pembrolizumab therapy.
• Subjects can either have progressed, had no response, or intolerance to prior cancer therapy. Patients must have recovered from all clinically significant treatment-related toxicities to grade 1 or less, except chemotherapy-associated peripheral neuropathy (motor or sensory), or endocrine-related AE, in which recovery to ≤ Grade 2 is allowed. For endocrine-related AEs, physiological doses of replacement therapy (e.g., levothyroxine, insulin, hydrocortisone, or other replacement therapy for adrenal or pituitary insufficiency, etc.) are allowed.
• No limit on prior lines of therapy for metastatic disease. Prior chemotherapy, immunotherapy (including pembrolizumab) or molecularly targeted therapy must have been completed at least 3 weeks prior to initiating study treatment. Prior palliative radiation must have been completed at least 2 weeks prior to initiating study treatment.
• 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 are eligible.
• All subjects must have an ECOG performance status of 0-1. 10 All subjects must have a life expectancy of ≥ 6 months at the time of initiating study treatment.
• \. Subjects must demonstrate adequate organ function as defined below:
• Absolute neutrophil count (ANC) ≥1,000 cells / μL
• Absolute lym75,000 cells/μL

You may not qualify if:

• Subjects who have autoimmune diseases that require immunosuppressive medications other than prednisone ≤ 10 mg daily or equivalent. Physiological doses of replacement therapy (e.g., levothyroxine, insulin, hydrocortisone, or other replacement therapy for adrenal or pituitary insufficiency, etc.) are not considered a form of immunosuppressant and are allowed.
• 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).
• Is receiving systemic steroid therapy (\> 10 mg prednisone oral daily or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 3 weeks earlier.
• Has had prior chemotherapy, targeted therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has known untreated, symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases requiring treatment, and are not using steroids (\> 10 mg prednisone oral daily or equivalent) for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

Sponsors & Collaborators

• Tianhong Li: lead
• National Cancer Institute (NCI): collaborator
• LabyRx Immunologic Therapeutics: collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Related Publications (1)

• Ma W, Zeng J, Montoya DJ, Toomey K, Zhou C, Chen S, Liu D, Babich M, Radosevich JA, Li T. Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer. Cancers (Basel). 2023 Feb 1;15(3):924. doi: 10.3390/cancers15030924.

  PMID: 36765881 RESULT

MeSH Terms

Conditions

Adenocarcinoma; Neoplasm Metastasis

Interventions

Cancer Vaccines; sargramostim; Colony-Stimulating Factors; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vaccines; Biological Products; Complex Mixtures; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Tianhong Li

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 19, 2021
• First Posted: November 1, 2021
• Study Start: October 13, 2021
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2030
• Last Updated: May 21, 2024

Record last verified: 2024-05

Locations

US (1)