Personalized Immunotherapy in Adults With Advanced Cancers Immunotherapy in Adults With Advanced Cancers

A Phase 1b Safety and Feasibility Study of Personalized Immunotherapy in Adults With Advanced Cancers

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.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: Personalized Vaccine; Drug: Pembrolizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • UCSD Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Personalized vaccine and anti- PD-1 administered concurrently at the start of study therapy.; Personalized vaccine and anti- PD-1 administered concurrently at the start of study therapy. Personalized vaccine will be administered by subcutaneous injection. Vaccine will be administered every three weeks for a total of three doses. Vaccine may continue to be administered at 3 week intervals for an additional 9 doses if there is no evidence of disease progression. Treatment for up to 9 doses may continue past progression if the treating physician feels there is continued benefit.	Drug: Personalized Vaccine; Vaccine was constructed for each subject that express multiple candidate tumor-derived neoantigens. Administered intramuscular injection every 3 weeks.; Drug: Pembrolizumab; Pembrolizumab was administered intravenous (IV) infusion every 3 weeks.; Other Names: Keytruda; Anti- PD-1
Experimental: Arm B: Anti-PD-1 antibody for 6 weeks followed by personalized vaccine therapy.; Anti-PD-1 antibody for 6 weeks followed by personalized vaccine therapy. Personalized vaccine will be administered by subcutaneous injection. Vaccine will be administered every three weeks for a total of three doses. Vaccine may continue to be administered at 3 week intervals for an additional 9 doses if there is no evidence of disease progression. Treatment for up to 9 doses may continue past progression if the treating physician feels there is continued benefit.	Drug: Personalized Vaccine; Vaccine was constructed for each subject that express multiple candidate tumor-derived neoantigens. Administered intramuscular injection every 3 weeks.; Drug: Pembrolizumab; Pembrolizumab was administered intravenous (IV) infusion every 3 weeks.; Other Names: Keytruda; Anti- PD-1
Experimental: Arm C: Personalized vaccine & anti- PD-1 administered concurrently in a boosted schedule; Personalized vaccine and anti- PD-1 administered concurrently in a boosted schedule at the start of study therapy. Personalized vaccine will be administered by intramuscular injection. Vaccine will be administered three weekly priming vaccine doses, followed by six vaccine doses administered every three weeks. Vaccine may continue to be administered at 3 week intervals for an additional 18 doses if there is no evidence of disease progression. Treatment for up to 9 doses may continue past progression if the treating physician feels there is continued benefit.	Drug: Personalized Vaccine; Vaccine was constructed for each subject that express multiple candidate tumor-derived neoantigens. Administered intramuscular injection every 3 weeks.; Drug: Pembrolizumab; Pembrolizumab was administered intravenous (IV) infusion every 3 weeks.; Other Names: Keytruda; Anti- PD-1
Experimental: Arm D: Personalized vaccine alone, in a boosted schedule at the start of study therapy.; Personalized vaccine alone, in a boosted schedule at the start of study therapy. Personalized vaccine will be administered by intramuscular injection. Vaccine will be administered three weekly priming vaccine doses, followed by six vaccine doses administered every three weeks. Vaccine may continue to be administered at 3 week intervals for an additional 18 doses if there is no evidence of disease progression. Treatment for up to 9 doses may continue past progression if the treating physician feels there is continued benefit.	Drug: Personalized Vaccine; Vaccine was constructed for each subject that express multiple candidate tumor-derived neoantigens. Administered intramuscular injection every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related Adverse Events	Number of Treatment-related Adverse Events	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response	RECIST 1.1 - Overall Response	1 year

Collaborators and Investigators

• Sponsor: Aaron Miller
• Investigators: Principal Investigator: Aaron Miller, MD, PhD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Actual): December 12, 2022
• Study Completion (Actual): January 27, 2025

Study Registration Dates

• First Submitted: June 13, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; vaccine; Keytruda; solid tumor; pembrolizumab; personalized cancer vaccine; neoantigen; personalized immunotherapy
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; spartalizumab
• Other Study ID Numbers: 180410

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No