Advanced Cancer
Conditions
Keywords
immunotherapy, personalized cancer vaccine, personalized immunotherapy, pembrolizumab, Keytruda, cancer, neoantigen, solid tumor, vaccine
Brief summary
The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and are not candidates for curative therapy.
Detailed description
The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and are not candidates for curative therapy. This 'personalized' vaccine will use information gained from specific characteristics of your own cancer. It is known that cancer has mutations (changes in genetic material) that are specific to an individual and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune (protective) responses, which may help your body fight any tumor cells that could cause your cancer to come back in the future. The study will examine the safety of the vaccine when given at several time points and will examine your blood cells for signs that the vaccine induced an immune response. The personalized vaccine will be given in combination with an anti-PD1 antibody, pembrolizumab, which is used with the intention to increase anti-cancer immunity (protection). Pembrolizumab is a type of drug that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the "brakes" on the immune system are released and T cells are able to kill cancer cells better. This personalized vaccine is considered experimental because this is not an FDA approved therapy for cancer. Pembrolizumab is FDA approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma (cHL), primary mediastinal large b-cell lymphoma (PMBCL), urothelial carcinoma, tumor mutational burden-high (TMB-H) cancer, cutaneous squamous cell carcinoma (cSCC), triple-negative breast cancer (TNBC), microsatellite instability-high (MSI-H) or mismatch repair deficient cancer, microsatellite instability-high or mismatch repair deficient colorectal cancer (CRC), gastric cancer, esophageal cancer, cervical cancer, and hepatocellular carcinoma (HCC), merkel cell carcinoma (MCC), renal cell carcinoma (RCC), endometrial carcinoma. Pembrolizumab is considered experimental (investigational) for the treatment of all other cancer types.
Interventions
Vaccine was constructed for each subject that express multiple candidate tumor-derived neoantigens. Administered intramuscular injection every 3 weeks.
DRUGPembrolizumab
Pembrolizumab was administered intravenous (IV) infusion every 3 weeks.
Sponsors
Aaron Miller
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented incurable solid tumor \[excluding lymphoma\]. * Measurable disease as defined by RECIST 1.1 * Progressed on or be intolerant to therapies that are known to provide clinical benefit. * Non-measurable disease by RECIST 1.1 and high-risk (\>50% over 5 years) of mortality * ECOG Performance Status ≤ 1. * At least one tumor site accessible for biopsy. * Adequate organ function * Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.
Exclusion criteria
* Patient has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. * Known or suspected allergy or hypersensitivity to any component of vaccine. * Has a known history of Human Immunodeficiency Virus (HIV). * Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. (Individuals who are hepatitis C antibody positive may be enrolled if negative viral load confirmed). * History of autoimmune disease including: inflammatory bowel disease (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g. Wegener's granulomatosis); central nervous system or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barré syndrome, myasthenia gravis, multiple sclerosis). Individuals with vitiligo, Sjogren's Syndrome, interstitial cystitis, Graves' or Hashimoto's Disease, celiac disease, DM1, hypothyroidism stable on hormone replacement, or any autoimmune disease without symptoms and not requiring active therapy for at least 2 years will be allowed with Study Medical Monitor's approval. * Has a known history of active TB (Bacillus Tuberculosis). * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * History of receiving a solid organ transplant or allogeneic bone marrow transplant. * Unable or unwilling to withhold or discontinue any prohibited or restricted medications/procedures for the specified windows during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related Adverse Events | 1 year | Number of Treatment-related Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response | 1 year | RECIST 1.1 - Overall Response |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAaron Miller, MD, PhD
University of California, San Diego
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54 Years STANDARD_DEVIATION 9.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Primary Cancer Site Breast | 2 Participants |
| Primary Cancer Site Colon | 4 Participants |
| Primary Cancer Site Eye and Orbit | 1 Participants |
| Primary Cancer Site Lip, Oral Cavity and Pharynx | 1 Participants |
| Primary Cancer Site Other Digestive Organ | 1 Participants |
| Primary Cancer Site Other Urinary | 0 Participants |
| Primary Cancer Site Ovary | 0 Participants |
| Primary Cancer Site Pancreas | 0 Participants |
| Primary Cancer Site Soft Tissue | 1 Participants |
| Primary Cancer Site Stomach | 1 Participants |
| Primary Cancer Site Unknown Sites | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 5 | 0 / 0 | 9 / 13 | 1 / 7 |
| other Total, other adverse events | 5 / 5 | 0 / 0 | 13 / 13 | 7 / 7 |
| serious Total, serious adverse events | 2 / 5 | 0 / 0 | 3 / 13 | 0 / 7 |
Outcome results
None listed