Testing the SurVaxM Vaccine for Lung Cancer Prevention

PRIMARY OBJECTIVE:

I. To evaluate the effect of SVN53-67/M57-KLH peptide vaccine (SurVaxM) administration on the generation of a systemic anti-survivin immune response.

SECONDARY OBJECTIVES:

I. To assess the proportion of participants needing a 3-month booster dose to achieve seroconversion.

II. To assess the proportion of participants mounting a cellular immune response to SurVaxM vaccination.

III. To assess the safety profile of SurVaxM administration in this population.

EXPLORATORY OBJECTIVES:

I. To associate participants' demographic and clinical characteristics with outcomes (seroconversion or needing the 3-month booster).

II. Correlation of human leukocyte antigen (HLA) typing and the association of HLA types to humoral and/or cellular responses.

OUTLINE:

Patients receive SurVaxM with montanide ISA 51 VG (montanide) subcutaneously (SC) followed by sargramostim SC on day 0, week 2, week 4, and week 6. Patients then receive a booster dose of SurVaxM with montanide SC followed by sargramostim SC on week 18. Patients also undergo collection of blood samples throughout the trial.

After completion of study intervention, patients are followed up at weeks 20 and 24.

• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection: Undergo collection of blood samples
• Montanide ISA 51 VG (Drug): Given SC
• Questionnaire Administration (Other): Ancillary studies
• Sargramostim (Biological), also known as 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin: Given SC
• SVN53-67/M57-KLH Peptide Vaccine (Biological), also known as SurVaxM: Given SC

Primary outcomes

• Seroconversion rate [Up to week 20]: Seroconversion rate will be summarized as the frequency and proportion of participants who achieved sufficient seroconversion, which will be reported with the corresponding 95% confidence intervals. A one-sample exact test for one proportion will be used to test whether seroconversion rate exceeds the unacceptably low rate of 50%.

Secondary outcomes

• Proportion of participants who require a 3-month booster to achieve seroconversion [At week 18]: Proportions will be reported with the corresponding confidence intervals.
• Proportion of participants who achieve seroconversion [By 3 months]: Proportions will be reported with the corresponding confidence intervals.
• Proportion of participants who do not achieve seroconversion at 3 months but achieve seroconversion 2-4 weeks after receiving a 3-month booster [Up to week 20]: Proportions will be reported with the corresponding confidence intervals.
• Proportion of participants who do not achieve seroconversion [Up to week 20]: Proportions will be reported with the corresponding confidence intervals.
• Cellular responses to the administration of SVN53-67/M57-KLH peptide vaccine [Before the administration of the first dose, 2-4 weeks after completion of the four priming doses, prior to receiving the booster, and 2-4 weeks after completion of the booster]: Will be measured on peripheral blood mononuclear cells. Will tabulate the proportion of participants mounting a cellular response using flow cytometry.
• Incidence of adverse events [Up to week 24]: Participants will also be provided with a participant diary, thermometer, and injection site reaction measuring tools to assist in collection and documentation of adverse events post-injection. All adverse events attributable to the vaccine as well as their severity will be reported in a descriptive format. The incidence rate and severity of each attributable adverse event will be tabulated and reported. Adverse events will be assessed using Common Terminology Criteria for Adverse Events version 5.0.

Other outcomes

• Seroconversion rate [Up to week 20]: Will perform exploratory analyses associating participants' demographic and clinical characteristics with outcomes using Wilcoxon ranksum tests to compare continuous variables between responders and non-responders using Fisher's exact test or chi-squared test to compare categorical variables between responders and non-responders. Multivariable logistic regression models will be used to examine the effects of multiple risk factors simultaneously.
• Proportion of participants who require a 3-month booster to achieve seroconversion [At week 18]: Will perform exploratory analyses associating participants' demographic and clinical characteristics with outcomes using Wilcoxon ranksum tests to compare continuous variables between responders and non-responders using Fisher's exact test or chi-squared test to compare categorical variables between responders and non-responders. Multivariable logistic regression models will be used to examine the effects of multiple risk factors simultaneously.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Former and current smokers (male and female) with a >= 20 pack year smoking history
* Prostate, Lung, Colorectal and Ovarian (PLCO)m2012 Lung Cancer Risk Prediction Score > 1.34%
* Participants >= 18 years old will be enrolled. Because no dosing or adverse event (AE) data are currently available on the use of SurVaxM in participants < 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable
* Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%)
* Platelets >= 100,000/microliter
* Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

  * Note: Higher total bilirubin levels (=< 3 mg/dL) can be allowed if due to known benign liver condition, i.e. Gilbert's
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =< 1.5 x institutional upper limit of normal
* Serum creatinine =< 1.5 x institutional upper limit of normal
* The effects of SurVaxM plus montanide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* History of autoimmune disease necessitating systemic immunosuppression, immunodeficiency, and/or organ allograft
* Participants may not be receiving any other chemotherapy (except hormonal agents), immunotherapy or investigational agent, or any immunosuppressive agent, including systemic steroids, including those given after organ transplant
* Participants with current or prior malignancy except for the following:

  * Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years before screening and felt to be at low risk for recurrence by treating physician
  * Adequately treated carcinoma-in-situ or basal cell carcinoma of the skin without current evidence of disease
  * Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer
  * Prior or current malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (e.g., localized prostate cancer) may be included
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to montanide or granulocyte-macrophage colony-stimulating factor (GM-CSF)
* Uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because of the unknown effects of SurVaxM plus montanide on the fetus. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with SurVaxM plus montanide, breastfeeding should be discontinued if the mother is treated with SurVaxM plus montanide
* Individuals participating in another interception trial with an immunomodulatory agent will be excluded from participation in this trial for a washout period of 6 months

• Saikrishna S Yendamuri, Principal investigator, Northwestern University

NIH grants: P30CA060553, UG1CA242643