All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

A single subject will be enrolled at each dose level in the single agent arm until any ≥ Grade 2 treatment-emergent adverse event (TEAE) is observed in the first cycle.

Then dosage escalation will follow a traditional 3+3 dose escalation design.

Each successive group of patients will be enrolled at an incrementally higher dosage until the Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D) of single agent BDB001 is reached.

In the combination arm of the study, a standard 3+3 dose escalation design will be utilized for all dose levels.

When the MTD or RP2D of single agent BDB001 is reached, the first dose level cohort of the combination arm will begin. Once the MTD or RP2D in combination has been determined, twenty additional subjects will be enrolled in the expansion phase of the study.

BDB001

Pembrolizumab is a potent humanized monoclonal antibody with high specificity of binding to the PD 1 receptor. Pembrolizumab has an acceptable preclinical safety profile and is approved as an IV therapy for a variety of advanced malignancies.

Harry Raftopoulos, MD

Phase 1 Open-Label Dose Escalation Study of BDB001 as a Single Agent and in combination with Pembrolizumab in Subjects with Advanced Solid Tumors

This clinical trial is a study of an experimental drug called BDB001. BDB001 is a Toll-like receptor (TLR) agonist that activates the immune system.

The primary objectives of this study are to evaluate the safety and tolerability of BDB001 as a single agent and in combination with pembrolizumab and to determine the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D) when given in combination with pembrolizumab in subjects with advanced solid tumors.

This is a multi-center, open-label, dose escalation/dose expansion Phase 1 study of BDB001 as a single agent and in combination with pembrolizumab in subjects with histologically-confirmed, incurable, unresectable or metastatic solid tumors that have relapsed or are refractory to standard therapies or for whom there is no approved therapy.

The study will be conducted in two separate but independent dose escalation arms: a single agent arm (BDB001 alone) and a combination arm (BDB001 in combination with pembrolizumab).

Participants will be allowed to continue treatment beyond study termination until occurrence of significant treatment-related toxicity, progressive disease or discontinuation criteria are met.

BDB001 followed by combination treatment with KEYTRUDA®

BDB001-101: Clinical Study of BDB001 as a Mono-therapy or in Combination With Pembrolizumab

Phase 1 Open-Label Dose Escalation Study of BDB001 as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Safety and tolerability of BDB001 as a single agent and in combination with pembrolizumab as measured by the incidence of adverse events and any dose limiting toxicity

Determination of the maximum tolerated dose by assessing the frequency of BDB001-related and BDB001 and pembrolizumab-related adverse events using CTCAE version 4.03 to categorize adverse event severity

Radiographic determination of tumor response in subjects dosed with BDB001 and BDB001 and pembrolizumab using irRECIST

Merck Sharp & Dohme LLC

Eikon Therapeutics

Atezolizumab

This part of the study will follow a traditional 3+3 dose escalation design.

Each successive group of patients will be enrolled at an incrementally higher dosage until the Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D) of BDB001 with atezolizumab is reached.

At the end of the dose escalation part of the study, the BDB001 dose to be used in combination with atezolizumab in the expansion part of the study will be established after thorough review of all available safety, preliminary efficacy, PK and PD data.

A biologically active dose will be selected that is either the MTD, if one was established in the escalation part, or an RP2D if no MTD was established. Approximately 20 additional subjects will initially be enrolled in the dose expansion part.

Atezolizumab is a is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1). Atezolizumab has an acceptable preclinical safety profile and is approved as an IV therapy for a variety of advanced malignancies.

A Phase 1 Open-label Dose Escalation Study of BDB001 in Combination with Atezolizumab in Subjects with Advanced Solid Tumors

This clinical trial is a study of an experimental drug called BDB001. BDB001 is a Toll-like receptor (TLR) agonist that activates the immune system.

The primary objectives of this study are to evaluate the safety and tolerability of BDB001 in combination with atezolizumab (Tecentriq) in subjects with unresectable or metastatic solid tumors who have relapsed or are refractory to standard treatment or for whom there is no approved therapy.

This is a multi-center, open-label, dose escalation/dose expansion Phase 1 study of BDB001 in combination with atezolizumab.

The study will be conducted in two separate but independent parts: a dose escalation part with BDB001 and atezolizumab and a dose expansion part of BDB001 in combination with atezolizumab.

BDB001-102: Open Label Dose Escalation of BDB001 in Combination w Atezolizumab

Phase 1 Open-Label Dose Escalation Study of BDB001 as a Single Agent and in Combination With Atezolizumab in Subjects With Advanced Solid Tumors

Safety and tolerability of BDB001 in combination with atezolizumab as measured by the incidence of adverse events and any dose limiting toxicities (DLT)

Determination of the MTD or RP2D by assessing the frequency and severity of adverse events related to BDB001 when given in combination with atezolizumab using CTCAE version 5.0 to categorize adverse event severity

Radiographic determination of tumor response in subjects dosed with BDB001 and atezolizumab using irRECIST

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Vaccines

Resiquimod

Immunologic Factors

1 ml of gp100 peptide vaccine and 1 ml of MAGE-3 peptide vaccine daily for 8 weeks with R848 Gel applied to gp100 injection site immediately. Injections given intradermally and subcutaneously at 2 separate sites in separate extremities. Half of each dose given one way, and half given the other way. Vaccines given on the same day. Participant receives a total of 4 injections each week.

After 8 weeks, if participant has melanoma lesions, R848 applied to half of the lesions on body for 16 weeks.

1 ml of gp100 peptide vaccine and 1 ml of MAGE-3 peptide vaccine daily for 8 weeks. Injections given intradermally and subcutaneously at 2 separate sites in separate extremities. Half of each dose given one way, and half given the other way. Vaccines given on the same day. Participant receives a total of 4 injections each week.

After 8 weeks, if participant has melanoma lesions, R848 applied to half of the lesions on body for 16 weeks.

1 ml of gp100 peptide vaccine: 0.5 ml administered intradermally and the other 0.5 ml subcutaneously in the same extremity weekly (every 7 days +/- 2 days) for 8 weeks.

gp100

Applied to the gp100 vaccine injection site immediately following the injection, allowed to air dry for 30 minutes then covered with gauze dressing.

R848 gel

1 ml of MAGE-3 peptide vaccine: 0.5 ml administered intradermally and the other 0.5 ml subcutaneously in the same extremity weekly (every 7 days +/- 2 days) for 8 weeks.

MAGE-3

Michael A. Davies, PHD

The goal of this clinical research study is to learn if the vaccines, gp100(g209-2M), and MAGE-3, when given in combination with resiquimod (R848), can help to stimulate the immune system against melanoma.

The Study Drug/Vaccines:

Resiquimod (R848) is designed to increase the production of antigen-specific T-cells, to activate immune cells, and to increase T-cells going into the tumor, which may cause the tumor cells to die.

gp100(g209-2M) and MAGE-3 are vaccines designed to stimulate immune cells, also called T-cells, which may help the immune system to recognize and kill melanoma cells.

Study Groups:

If you are found to be eligible to take part in this study, and you have metastatic melanoma, you will be assigned to Group 3. If you have had the melanoma removed and want to be treated to try to keep it from coming back, you will be randomly assigned (as in the flip of a coin) to Group 1 or 2.

* If you are in Group 1, you will receive the vaccines gp100(g209-2M) and MAGE-3 and R848 for 8 weeks. After 8 weeks, if you have melanoma lesions, you will apply R848 to half of the lesions on your body for 16 weeks.
* If you are in Group 2, you will receive only the vaccines (gp100(g209-2M) and MAGE-3) only for 8 weeks. After 8 weeks, if you have melanoma lesions, you will apply R848 to half of the lesions on your body for 16 weeks.
* If you are in Group 3, you will receive the vaccines gp100(g209-2M) and MAGE-3 and R848 for 8 weeks. After 8 weeks, if you have melanoma lesions, you will apply R848 to half of the lesions on your body for 16 weeks.

After 8 weeks, if you no longer have melanoma lesions, you will have completed the study treatment.

Study Drug/Vaccine Administration:

Once a week for 8 weeks, you will receive the vaccines, gp100(g209-2M) and MAGE-3, intradermally (through a needle into your skin) and subcutaneously (through a needle under your skin) at 2 separate sites in separate extremities. Half of each dose will be given one way, and half given the other way. These vaccines will also be given on the same day. You will receive a total of 4 injections each week.

If you are in Group 1, every time you have the vaccine injection, R848 will be applied as a gel over the gp100(g209-2M) injection site. The R848 gel will be allowed to air dry for 30 minutes and then covered with a gauze dressing which remain on overnight.

After 8 weeks, for participants with melanoma lesions, 2 times a week for 16 weeks, you will apply the R848 gel to half of the lesions on your body. You will be given written instructions and a "hands-on" demonstration on how to apply the gel. You will also be given a worksheet to help you with applying the gel.

Study Visits:

One day after your first dose of vaccine (Day 2), you will have a punch biopsy of the vaccine injection site to check your immune system. A punch biopsy is when a hollow instrument that is used to remove a small coin-shaped sample of tissue.

At Week 2, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* Your performance status will be recorded.
* Blood (about 1 teaspoon) will be drawn for routine tests.
* Blood (about 4 tablespoons) will be drawn to study your immune response to the vaccine combinations.
* You will have a punch biopsy of the injection site to check your immune system the day after the vaccine is given.

Every 4 weeks, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* Your performance status will be recorded.
* Blood (about 1 teaspoon) will be drawn for routine tests.
* Blood (about 4 tablespoons) will be drawn to study your immune response to the vaccine combinations.

Every 8 weeks, for participants with metastatic disease, the following tests and procedures will be performed:

* You will have CT or PET/CT scans of the chest, abdomen, and pelvis to check the status of the disease.
* The tumors will be measured and photographed. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are tumors on your face.
* If the doctor thinks it is necessary, the tumors will be measured by CT scan.
* If the doctor thinks it is needed, you will have an MRI/CT of the brain to check the status of the disease.

The day after you first start the gel (Week 8), you will have 2 punch tumor biopsies to check your immune system. One biopsy will be of a lesion with the R848 and one without, if it is available. For participants without disease, the study will be completed and your follow-up will be decided by your doctor.

At Week 0 (before vaccine is started), after treatment at Week 8 (+/- 1 week)., and Week 16 (+/- 1 week), white blood cells will be collected by leukapheresis to test for antibodies. If you have the leukapheresis, blood (about 2 teaspoons) will be drawn as well. If you do not have leukapheresis, blood (about 4 tablespoons) will be drawn instead.

The leukapheresis procedure is research-related and would not be performed as standard of care if you were not on study. Blood for the leukapheresis will be taken through a needle in a vein in one of your arms. A solution will be added to keep your blood from clotting while it goes through the machine that collects and removes white blood cells from your blood. The remaining blood is returned to you through a needle in a vein of your other arm. This is may take up to 3-4 hours. Although several pints of blood will go through the machine, only about 1/2 a pint (1 cup) will be in the machine at any time. If you cannot have a needle in your vein, this blood will be removed thorough a central venous catheter (CVC). A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. You will be given another informed consent document to sign, which describes the risks of the CVC and the care involved.

Length of Study:

You will continue to receive treatment for up to 4 6 months, as long as you may benefit from the study and are responding to the gel. You will be taken off study if the disease gets worse or you experience any intolerable side effects. If you are in the group without disease, you will not receive the study treatment.

Follow-Up:

All three groups will be called 1 time a month for 12 months after coming off the study drugs to check on the status of the disease.

This is an investigational study. The study drugs/vaccines gp100(g209-2M), MAGE-3, and R848 are not FDA approved or commercially available. At this time, they are only being used in research.

Up to 71 participants will take part in this study. All will be enrolled at MD Anderson.

Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist

Activation of pDCs at the Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist

T-cell response to gp100(g209-2M) +/- MAGE3 measured at 8 weeks using a tetramer/multimer assay measured by flow cytometry. Based on the number of gp100(g209-2M) +/- MAGE3 T-cells measured, categorized as either immune responders or immune non-responders. T-cell response to the gp100(g209-2M) + /- MAGE3 peptide in each participant defined as ≥0.1% gp100(g209-2M) tetramer+ cells in the CD8+ T-cell population or ≥0.1% MAGE3 multimer cells in the CD4+ T-cell population.

Differences determined in each of these parameters between the pretreatment and post-treatment samples for each of the biopsied lesions for each participant.

M.D. Anderson Cancer Center

1 ml of gp100 peptide vaccine and 1 ml of MAGE-3 peptide vaccine daily for 8 weeks with R848 Gel applied to gp100 injection site immediately.

Group 1: GP100 and MAGE-3 + R848

1 ml of gp100 peptide vaccine and 1 ml of MAGE-3 peptide vaccine daily for 8 weeks.

Group 2: GP100 and MAGE-3

Group 3-Metastatic Melanoma: GP100 + MAGE-3 + R848

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Michael Davis, PHD., Chair, Melanoma Medical Oncology

The original PI is no longer in the institution. Due to the absence of the original PI is no longer in the institution and the data is unavailable. The analysis for the primary outcome measure the comparison of immune responses of vaccine+R848 to vaccine alone is not available. All efforts were made to retrieve data.

Comparison of Immune Responses of Vaccine+R848 to Vaccine Alone

The original PI is no longer in the institution. Due to the absence of the original PI is no longer in the institution and the data is not available. The analysis for the secondary outcome measure the composite of Immune Cell Infiltration for pDCs, mDCs, and NK cells in Tumor Biopsy Samples data is unavailable .All efforts were made to retrieve data.

Composite of Immune Cell Infiltration for pDCs, mDCs, and NK Cells in Tumor Biopsy Samples

Overall Study

Ocular Melanoma

Intraocular Melanoma

Anti-Infective Agents

Amino Acids

Poly ICLC

Interferons

Histidine

6MHP (200mcg of each peptide) and 300mcg of NeoAg-mBRAF will be co-administered locally with 0.9mg of polyICLC and CDX-1140. There will be a dose escalation of CDX-1140 (50mcg, 200mcg, 800mcg, 3.0mg). A vaccine containing all of these components will be given on days 1, 22, 43, and 64. The vaccine will be given subcutaneously/intradermally.

6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

6MHP

BRAF 586-614 (V600E) peptide to which a histidine has been added to the N-terminus, resulting in BRAF 585-614 (V600E).

NeoAg-mBRAF

PolyICLC

CDX-1140

Craig L. Slingluff, Jr., MD

This study evaluates whether it is safe to administer a peptide vaccine made of 6MHP and a mutated neoantigen peptide (BRAF585-614-V600E) combined with adjuvants. The adjuvants that will be used in this trial are a CD40 antibody (CDX-1140) and a toll-like receptor (TLR) 3 agonist (Poly-ICLC). The study will also investigate the effects of the vaccine and the adjuvants on the immune response. The investigators will monitor these effects by performing tests in the laboratory on participants' blood and skin tissue.

Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma)

Enhanced Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists in Patients With Melanoma

Number of participants with dose-limiting toxicities based on CTCAE v5.0

Number of participants with durable or persistent CD4+ Th1 responses to the melanoma vaccine at either day 85 or day 176, or both

Number of FoxP3+ CD4+ T cells per mm\^2 in vaccine site biopsies

Number of participants with circulating Tregs (CD4+ FoxP3+) as a proportion of circulating CD4 T cells

Number of participants with CD4+ T cell response; maximum increase after vaccination at any time point.

Number of participants with CD4+ T cell response to the melanoma peptides

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BDB001-101: Clinical Study of BDB001 as a Mono-therapy or in Combination With Pembrolizumab	NCT03486301	Tumor, Solid	BDB001 Pembrolizumab	18 Years -	Eikon Therapeutics
BDB001-102: Open Label Dose Escalation of BDB001 in Combination w Atezolizumab	NCT04196530	Tumor, Solid	BDB001 Atezolizumab	18 Years -	Eikon Therapeutics
BDB001-102: Open Label Dose Escalation of BDB001 in Combination w Atezolizumab	NCT04196530	Tumor, Solid	BDB001 Atezolizumab	18 Years -	Eikon Therapeutics
Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist	NCT00960752	Melanoma	gp100 R848 gel MAGE-3	18 Years -	M.D. Anderson Cancer Center
BDB001-101: Clinical Study of BDB001 as a Mono-therapy or in Combination With Pembrolizumab	NCT03486301	Tumor, Solid	BDB001 Pembrolizumab	18 Years -	Eikon Therapeutics
Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma)	NCT04364230	Melanoma Ocular Melanoma Uveal Melanoma	6MHP NeoAg-mBRAF PolyICLC CDX-1140	18 Years -	University of Virginia
Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma)	NCT04364230	Melanoma Ocular Melanoma Uveal Melanoma	6MHP NeoAg-mBRAF PolyICLC CDX-1140	18 Years -	University of Virginia
BDB001-102: Open Label Dose Escalation of BDB001 in Combination w Atezolizumab	NCT04196530	Tumor, Solid	BDB001 Atezolizumab	18 Years -	Eikon Therapeutics

Spots Global Cancer Trial Database for tlr

Every month we try and update this database with for tlr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tlr

Every month we try and update this database with for tlr cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tlr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.