Clinical Trials at the UC San Diego Sanford Stem Cell Clinical Center CIRM Alpha Clinic

Dose-escalation study of CRX100 in patients with Advanced Solid Tumors                                                   

This clinical study is an open-label, phase 1, dose-escalation study to determine the safety, tolerability, and pharmacokinetic (PK) properties of CRX100 in adult subjects with advanced solid tumors. Patients will be screened and evaluated to determine whether or not they meet stated inclusion criteria. Enrolled subjects will undergo leukapheresis to enable the ex vivo generation of autologous cytokine induced killer (CIK) cells. Patients with triple-negative breast cancer, colorectal cancer, hepatocellular carcinoma, osteosarcoma, epithelial ovarian cancer, and gastric cancer will be considered.

STATUS: Temporarily Closed to Enrollment

PI: Sandip Patel, MD

Contact Number: (858) 249-4020

Trial Sponsor: BioEclipse Therapeutics

A Pilot Study to Evaluate the Feasibility and Safety of Cytomegalovirus-Specific, Anti-HIV Chimeric Antigen Receptor (CMV-HIV CAR) T Cells in People Living With HIV 

Human immunodeficiency virus type 1 (HIV-1) causes a persistent infection that ultimately leads to acquired immunodeficiency syndrome (AIDS). Treatment of HIV-1 infection with combination anti-retroviral therapy (ART) suppresses HIV-1 replication to undetectable viral levels and saves lives. Nevertheless, ART cannot eradicate latent cellular reservoirs of the virus, and HIV-1 infection remains a life-long battle. Adoptive cellular immunotherapy using chimeric antigen receptor (CAR) engineered T cells directed against HIV-1 envelope subunit protein gp120 (HIVCAR T cells) may provide a safe and effective way to eliminate HIV-infected cells.

However, the number of HIV-infected cells is low in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of HIV-1-infected individuals are CMV-seropositive and CMV-specific T cells have been shown to persist. To overcome the CAR T cells low persistence issue, we propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo. The overall hypothesis of this first-in-human Phase 1, open-label, single-arm study is that endogenous immune signals to CMV-specific T cells can maintain the presence of autologous bispecific CMV/HIV-CAR T cells in healthy people living with HIV-1 (PLWH), and achieve long-term remission in the presence of ART.

Human immunodeficiency virus type 1 (HIV-1) causes a persistent infection that ultimately leads to acquired immunodeficiency syndrome (AIDS). Treatment of HIV-1 infection with combination anti-retroviral therapy (ART) suppresses HIV-1 replication to undetectable viral levels and saves lives. Nevertheless, ART cannot eradicate latent cellular reservoirs of the virus, and HIV-1 infection remains a life-long battle. Adoptive cellular immunotherapy using chimeric antigen receptor (CAR) engineered T cells directed against HIV-1 envelope subunit protein gp120 (HIV-CAR T cells) may provide a safe and effective way to eliminate HIV-infected cells. However, HIV-infected cells in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of individuals with HIV-1 are CMV-seropositive and CMV-specific T cells have been shown to persist at high frequency due to CMV antigen stimulation. To overcome the CAR T cells low persistence issue, we propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo. The overall hypothesis of this first-in-human, open-label, single-arm, pilot study is that endogenous immune signals to CMV-specific T cells can maintain the presence of autologous bispecific CMV/HIV-CAR T cells in healthy people living with HIV-1 (PLWH). Based on the results of this safety study, CMV vaccine and analytic treatment interruption will be evaluated with the CMV/HIV-CAR T cell investigational product in a subsequent protocol.

The trial is a first-in-human, pilot study to evaluate the feasibility and safety and determine the maximum tolerated dose (MTD)/recommended Phase II dose (RP2D) of CMV/HIV-CAR T cells in PLWH. Eligible participants will temporarily interrupt their ART regimen for 4 days prior to leukapheresis to prevent residual cell drug levels that could inhibit lentiviral transduction of the T cells during CAR T cell manufacturing. Participants will resume their ART regimen immediately after leukapheresis. If the manufacturing is not successful, a second apheresis may be scheduled no sooner than 3 weeks later with temporary interruption of ART regimen for 4 days prior to leukapheresis. Participants will resume their ART regimen immediately after leukapheresis. Once the final cell product is released, participants will receive a single intravenous (IV) infusion of autologous CMV/HIV-CAR T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cells may be explored.

STATUS: Active / Recruiting and Enrolling

PI: Davey Smith, MD

Contact Number: (619) 542-3740 (Marvin Hanarshiro)

Recruitment Website 

Trial Sponsor: City of Hope Medical Center

An Investigator-initiated Clinical Trial of Safety and Efficacy of Transplantation of Human Induced Pluripotent Stem Cell-derived Dopaminergic Progenitors (CT1-DAP001) for Parkinson's Disease (Phase I/II)                                                   

To evaluate the safety and efficacy of transplantation of human induced pluripotent stem cell-derived dopaminergic progenitors, CT1-DAP001, into the corpus striatum in patients with Parkinson's disease. Single-center, open-label, uncontrolled. The primary objective of this study is to evaluate the safety of CT1-DAP001 in subjects with Parkinson's disease by determining the incidence and severity of adverse events, especially graft expansion, after transplantation into the corpus striatum. Other objectives are to evaluate the efficacy of CT1-DAP001 through the assessment of Parkinson's disease symptoms and clinical severity or progression.

STATUS: Recruiting

PI: Josheph Ciacci, MD

Contact Number: (858) 249-4020

Trial Sponsor: University of California, San Diego & Sumitomo Dainippon Pharma

A Study of Focal Epilepsy; Drug Resistant Mesial Temporal Lobe Epislepsy

This clinical trial is designed to test whether a single stereotactic intracerebral administration of inhibitory nerve cells into subjects with drug-resistant mesial temporal lobe epilepsy is safe (frequency of adverse events) and effective (seizure frequency).

Subjects will undergo a single stereotactic intracerebral administration of neural cells, called interneurons, that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).

Subjects will then take medicines to partially suppress their immune system (aimed to prevent the body from rejecting the cells) for 1 year. Safety, tolerability, evidence of neural cell viability and local inflammation (using MRI scans of the brain), and effects on epilepsy disease symptoms will be assessed for 2 years post-transplant. Subjects will be followed for an additional 13 years with quarterly phone contact and annual visits.

A First-In-Human (FIH) Study of Inhibitory Interneurons (NRTX- 1001) in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (MTLE)

STATUS: Active / Enrolling

PI: Jerry Shih, MD

Contact Number: (858) 249-4020

Trial Sponsor: Neurona Therapeutics

A Long-Term Follow-Up Study of Participants With Cystinosis Who Previously Received CTNS-RD-04

This is a multinational, long-term follow-up study to assess the long-term safety and durability of CTNS-RD-04 treatment in participants who received a single dose administration of lentiviral gene therapy. No investigational product will be administered in this study. Participants will continue periodic safety and efficacy assessments in this long-term follow-up study up to 15 years from the initial date of CTNS-RD-04 infusion.

Participants enrolled in a study where the individual received CTNS-RD-04 will be offered participation in the CTNS-RD-04-LTF01 study. The Baseline visit for the CTNS-RD-04-LTF01 study will likely coincide with the final visit in the parent study. Participants confirmed eligible for the CTNS-RD-04-LTF01 study will be asked to return for study visits at approximately 6-month intervals for the first 4 years and annually thereafter for up to 11 years until a total of 15 years have elapsed during which time continued safety, engraftment, and efficacy of CTNS-RD-04 treatment will be assessed.

STATUS: Active / Enrolling by Invitation

PI: Bruce Barshop, MD, PhD and Stephanie Cherqui, PhD

Contact Number: (858) 249-4020

Trial Sponsor: UC San Diego and Novartis

A Screening Study to Collect Samples for TAA, HLA & HLA Loss of Heterozygosity in Patients With Metastatic Solid Tumors

TScan Therapeutics is developing cellular therapies across multiple solid tumors in which autologous participant-derived T cells are engineered to express a T cell receptor that recognizes cancer-associated antigens presented on specific Human Leukocyte Antigen (HLA) molecules. The purpose of this screening study is to collect samples to conduct HLA genotyping, HLA Loss of Heterozygosity (LOH) and expression of Tumor-associated Antigens (TAA) testing. These results will be used to determine if subjects meet the eligibility criteria for these parameters and could potentially be enrolled in a TScan clinical treatment study.

This multicenter screening study will be conducted to determine a subject's tumor antigen expression profile, HLA genotype and HLA LOH for TScan sponsored clinical treatment study(s). No treatment intervention will occur as part of this screening study.

Subjects will be required to provide a buccal swab to assess their HLA status. If they are positive for certain types of HLA, subjects will provide a saliva sample to assess HLA loss of heterozygosity. In parallel, archival tissue (less than 8 months old) will be needed to assess for tumor antigen expression. If archival tissue is older than 8 months, a fresh tumor biopsy will be required at the time of the second visit.

If eligible, subjects will be referred to appropriate available interventional trial(s) at the discretion of the Investigator.

STATUS: Active / Recruiting 

PI: Sandip Patel, MD

Contact Number: (858) 249-4020

Trial Sponsor: TScan Therapeutics

A Study of Dazostinag as Single Agent and Dazostinag in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors (iintune-1)

The main aim of this study is to check if people with advanced solid tumors have side effects from dazostinag, and to check how much dazostinag they can receive without getting significant side effects from it when given alone and in combination with pembrolizumab. The study will be conducted in two phases including a dose escalation phase and a dose expansion phase. In the dose escalation phase, escalating doses of dazostinag are being tested alone and in combination with pembrolizumab to treat participants who have advanced or metastatic solid tumors. In the dose expansion phase, dazostinag will be studied with pembrolizumab with or without chemotherapy in participants with untreated metastatic or recurrent, unresectable squamous cell carcinoma of head and neck (SCCHN) and in combination with pembrolizumab in third-line or later recurrent locally advanced or metastatic microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and third-line recurrent locally advanced or metastatic microsatellite stable/mismatch repair proficient (MSS/pMMR) colorectal cancer (CRC).

The drug being tested in this study is called dazostinag. Dazostinag is being tested to treat people who have advanced or metastatic solid tumors.

The study will enroll approximately 368 participants. Part 1 consists of an initial Safety Lead-in to Dose Escalation Phase; Part 2 and Part 3 compose the Expansion Phase in 2 specific indications namely, previously untreated metastatic or recurrent, unresectable SCCHN (Part 2) and third-line or later recurrent locally advanced or metastatic MSI-H/dMMR and third-line recurrent locally advanced or metastatic MSS/pMMR CRC (Part 3). Participants will be assigned to the following treatment groups in the respective Phases of the study:

• Part 1 (Dose Escalation Phase): Safety Lead-in + Dazostinag single agent (SA) [Part 1A] Dazostinag 0.1 milligram (mg) in the Safety Lead-in followed by Dazostinag as escalating doses (0.2 mg and above) in Part 1A
• Part 1B (Combination Dose Escalation Phase): Dazostinag as escalating doses (0.2 mg and above) + Pembrolizumab
• Japan Safety Lead-in: Dazostinag SA 5.0 mg in the Safety Lead-in+ Pembrolizumab. Additional dose levels of Dazostinag (such as 3.5 mg or 7.0 mg and higher) in combination with pembrolizumab may be explored during the Japan safety lead-in considering recommended dose for expansion (RDE1) as 5.0 mg and dose optimization.

Once a safe dose is recommended from Part 1, participants of select advanced or metastatic solid tumors will receive dazostinag in below defined cohorts in the expansion phase:

• Part 2A (SCCHN Combined Positive Score [CPS] ≥ 1 Dose Expansion Phase): Dazostinag + Pembrolizumab*
• Part 2B (SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab + Chemotherapy
• Part 3A (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSI-H/dMMR CRC
• Part 3B (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSS/pMMR CRC* *Dose optimization will be performed in either Part 2A SCCHN or Part 3B CRC.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 62.9 months. Participants will make multiple visits to the clinic, including 30 days after last dose of study drug for a follow-up assessment. Participants in Parts 2 and 3 will be followed for survival for up to 12 months after the last dose of study drug.

An Open-label, Dose Escalation, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-676 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors.

STATUS: Active / Recruiting 

PI: Sandip Patel, MD

Contact Number: (858) 249-4020

Trial Sponsor: Takeda Pharmaceutical Company, LTD

A Phase 1 Dose Escalation and Expanded Cohort Study of P-MUC1C-ALLO1 in Adult Subjects With Advanced or Metastatic Solid Tumors

A Phase 1, open label, dose escalation and expanded cohort study of P-MUC1C-ALLO1 in adult subjects with advanced or metastatic epithelial derived solid tumors, including but not limited to the tumor types listed below.

This is an open label, multi-center Phase 1 study that will follow a 3 + 3 design of dose-escalating cohorts of single and multiple doses of P-MUC1C-ALLO1 to determine a Recommended Phase 2 Dose (RP2D). P-MUC1C-ALLO1 is an allogeneic chimeric antigen receptor (CAR) T cell therapy designed to target cancer cells expressing Mucin1 cell surface associated C-Terminal (MUC1-C) antigen. Additional participants will be treated with P-MUC1C-ALLO1 at the determined RP2D.

Following enrollment, subjects will be treated with P-MUC1C-ALLO1 and will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated.

STATUS: Active / Recruiting 

PI: Peter Vu, MD

Contact Number: (858) 249-4020

Trial Sponsor: Poseida Therapeutics

A Study of TAK-500 With or Without Pembrolizumab in Adults With Select Locally Advanced or Metastatic Solid Tumors

This study is about TAK-500, given either alone or with pembrolizumab, in adults with select locally advanced or metastatic solid tumors.

The aims of the study are:

• to assess the safety profile of TAK-500 when given alone and when given with pembrolizumab.
• to assess the anti-tumor effects of TAK-500, when given alone and when given with pembrolizumab, in adults with locally advanced or metastatic solid tumors.

Participants may receive TAK-500 for up to 1 year. Participants may continue with their treatment if they have continuing benefit and if this is approved by their study doctor. Participants who are receiving TAK-500 either alone or with pembrolizumab will continue with their treatment until their disease progresses or until they or their study doctor decide they should stop this treatment.

The drug being tested in this study is called TAK-500. The study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of TAK-500 when used as a single agent (SA) and in combination with pembrolizumab in participants with locally advanced or metastatic solid tumors.

The study will be conducted in 2 phases: Dose Escalation and Dose Expansion Phase. The study will enroll approximately 313 participants (approximately 82 in the Dose Escalation Phase and approximately 231 in Dose Expansion Phase). The dose escalation phase will determine the recommended dose of TAK-500 along with the combination agents for the dose expansion phase. All the participants will be assigned to one of the 9 arms:

• Dose Escalation: TAK-500 Single Agent (SA)
• Dose Escalation: TAK-500 + Pembrolizumab
• Dose Expansion: 2L NSCLC: TAK-500 recommended dose 1 for expansion (RDE 1) + Pembrolizumab
• Dose Expansion: 2L NSCLC: TAK-500 recommended dose 2 for expansion (RDE 2) + Pembrolizumab
• Dose Expansion: 3L NSCLC: TAK-500 (RDE 1) SA
• Dose Expansion: 3L NSCLC: TAK-500 (RDE 2) SA
• Dose Expansion: 2L Pancreatic Adenocarcinoma: TAK-500 (RDE 1) + Pembrolizumab
• Dose Expansion: 2L Pancreatic Adeno: TAK-500 (RDE 1) SA
• Dose Expansion: 3L RCC: TAK-500 (RDE 1) + Pembrolizumab

This multi-center trial will be conducted globally. Participants with demonstrated clinical benefit may continue treatment beyond 1 year if approved by the sponsor.

An Open-label, Dose Escalation and Expansion, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of TAK-500, a Novel Stimulator of Interferon Genes Agonist, as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Select Locally Advanced or Metastatic Solid Tumors.

STATUS: Active / Recruiting 

PI: Sandip Patel, MD

Contact Number: (858) 249-4020

Trial Sponsor: Takeda Pharmaceutical Company, LTD

Claudin18.2 CAR-T (CT041) in Patients With Gastric, Pancreatic Cancer, or Other Specified Digestive Cancers

A Phase 1b/2, open label, multi-center, clinical study of Chimeric Antigen Receptor T Cells (CAR-T) targeting claudin18.2 in patients with advanced gastric, pancreatic or other specified digestive system cancers.

This is an open label, multi-center, Phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous claudin18.2 chimeric antigen receptor T-cell therapy in patients with advanced gastric, pancreatic or other specified digestive system cancers.

Following consent, patients must have tumor tissue evaluated by CLDN18.2 IHC assay. Patients meeting all eligibility criteria will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (CT041). Following manufacture of the drug product, subjects will receive preconditioning prior to CT041 infusion. All subjects will be asked to continue to undergo long-term gene safety follow-up.

Open-label, Multicenter, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous Anti-claudin 18.2 Chimeric Antigen Receptor T-cell Therapy in Subjects With Advanced Gastric, Pancreatic, or Other Specified Digestive System Cancers.

STATUS: Temporarily Closed to Enrollment 

PI: Gregory Bota, PhD

Contact Number: (858) 249-4020

Trial Sponsor: CARsgen Therapeutics

A Phase 1/2 Study Investigating the Safety and Efficacy of Autologous TAC T Cells in Subjects With Unresectable, Locally Advanced or Metastatic Claudin 18.2+ Solid Tumors TAC T-cells for the Treatment of Claudin 18.2 Positive Solid Tumors (TACTIC-3) (TACTIC-3)

TAC01-CLDN18.2 is a novel cell therapy that consists of genetically engineered autologous T cells expressing T-cell Antigen Coupler (TAC) that recognizes Claudin 18.2. TAC directs T-cells to the targeted antigen (CLDN 18.2), and once engaged with the target, activates them via the endogenous T cell receptor.

This is an open-label, multicenter Phase ½ study that aims to establish safety, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), pharmacokinetic profile and efficacy of TAC01-CLDN18.2.

The TAC technology is a novel approach to modifying T cells, herein referred to as TAC T cells, and using them in the treatment of solid tumors. TAC T cells are produced through genetic engineering, incorporating TAC receptors into a patient's own T cells. This redirects these enhanced T cells to specific cancer antigens, and upon recognition, activates them through the natural signaling pathways of the endogenous TCR.

In the TAC01-CLDN18.2 engineered T cell product; TAC T cells recognize the CLDN18.2, a tight junction protein present on the surface of tumor cells, where the protein expression is no longer limited to tight junctions and are visible to T cells to eradicate them. Consequently, it is hypothesized TAC01-CLDN18.2 will be potentially safe and active in treating patients with CLDN18.2+ solid tumors and provide a clinically meaningful therapeutic benefit in patient populations with high unmet medical need.

This is a first-in-human study investigating TAC01-CLDN18.2 to evaluate the safety, MTD or RP2D, PK, and efficacy in subjects with CLDN18.2+ solid tumors who have been treated with at least 2 lines of prior therapy in Phase 1 and after at least 2 lines and no more than 4 lines of prior therapy in Phase 2 (Note: in each phase, subjects with PDAC may have been treated with 1 line of prior antineoplastic therapy. In addition, subjects who are being treated with current lines of therapy, but not deriving benefit or not tolerating therapy, and have not progressed maybe also eligible as long as they have measurable disease at baseline as a starting reference point). In Phase 1, escalating doses of TAC01-CLDN18.2 will be evaluated to identify the RP2D using the classic 3+3 dose escalation study design.

In Phase 2, dose expansion groups will further evaluate the efficacy, safety, and PK of the MTD or RP2D for TAC01-CLDN18.2 in subjects with gastric and esophageal AC (Group A), PDAC (Group B), and mucinous ovarian and NSCLC cancers (Group C). In Phase 2, definitions of eligible CLDN18.2+ IHC expression levels will be based on analysis of data from Phase 1 for signals of clinical activity since there are no formal CAP/ASCO guidelines for CLDN18.2+ expression levels. In Phase 2, a Simon 2-stage design will be used to enroll up to 57 subjects in Group A and 22 subjects in Group C. Group B (PDAC) will enroll up to 10 subjects as an exploratory cohort due to the historically low ORRs observed in PDAC. The 10 treated subjects in Group B are designed to seek evidence of potential clinical activity in this difficult to treat CLDN18.2+ subpopulation of PDAC.

STATUS: Active / Recruiting and Enrolling

PI: Gregory Bota, PhD

Contact Number: (858) 249-4020

Trial Sponsor: Triumviara Immunologics

A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment

The purpose of the study is to evaluate the overall survival of participants treated with imetelstat compared to best available therapy with intermediate-2 or high-risk Myelofibrosis (MF) who are relapsed/refractory to Janus Kinase (JAK)-Inhibitor treatment.

This is a multicenter study with 2 arms, and will include 3 phases: a) screening phase of up to 28 days before randomization during which participants will complete a 14-day washout period from all prior therapies including JAK-inhibitor treatment, and the participant's eligibility will be reviewed; b) treatment phase, from randomization until study treatment (imetelstat or BAT) discontinuation; and c) post treatment follow-up phase, that begins when the participant discontinues treatment, and will continue until death, lost to follow-up, withdrawal of consent, or study end, whichever occurs first. Participants will be randomized (2:1) into 2 Arms (Arm A will receive imetelstat and Arm B will receive BAT).

Participants who meet progressive disease criteria and discontinue BAT, may crossover to receive imetelstat treatment after sponsor's approval.

A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients With Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK) Inhibitor.

STATUS: Active / Recruiting 

PI: Michael Choi, MD

Contact Number: (858) 249-4020

Trial Sponsor: Geron

A Study of CNTY-101 in Participants With CD19-Positive B-Cell Malignancies (ELiPSE-1)

ELiPSE-1 is a Phase 1, multi-center, dose-finding study to evaluate the safety, pharmacokinetics, and preliminary efficacy of CNTY-101 in participants with relapsed or refractory cluster of differentiation (CD)19-positive B-cell malignancies.

The ELiPSE-1 Study: A Phase 1, Multicenter, Open-Label Study of CNTY-101 in Subjects With Relapsed or Refractory CD19-Positive B-Cell Malignancies.

STATUS: Active / Recruiting 

PI: Benjamin Heyman, MD

Contact Number: (858) 249-4020

Trial Sponsor: Century Therapeutics

A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Subjects With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression (EVEREST-1)

The goal of this study is to test A2B530,an autologous logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), pancreatic cancer (PANC), non-small cell lung cancer (NSCLC), and other solid tumors that express CEA and have lost HLA-A*02 expression.

The main questions this study aims to answer are:

• Phase 1: What is the maximum or recommended dose of A2B530 that is safe for patients
• Phase 2: Does the recommended dose of A2B530 kill the solid tumor cells and protect the patient's healthy cells

Participants will be required to perform study procedures and assessments, and will also receive the following study treatments:

• Enrollment and Apheresis in BASECAMP-1 (NCT04981119)
• Preconditioning Lymphodepletion (PCLD) Regimen
• A2B530 Tmod CAR T cells at the assigned dose

This is a phase 1/2, multi-center, open-label study that enrolls adult subjects with recurrent unresectable, locally advanced, or metastatic (considered non-curative) CRC, NSCLC, PANC, or other solid tumors with CEA expression. Subjects must be germline HLA-A*02 heterozygous, with tumors that express CEA and somatic loss of HLA-A*02. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of A2B530 (after PCLD) in participants with solid tumor disease. The purpose of Phase 2 of this study is to determine the further safety and efficacy (how well it treats the solid tumor disease) of A2B530.

The treatment available for these cancers and other solid tumors can be toxic, debilitating, and fatal. In the recurrent unresectable, locally advanced, or metastatic setting, the intent of standard of care treatment is typically palliative rather than curative, and has not changed significantly in several decades. A2 Bio hypothesizes that A2B530 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express CEA and have LOH for HLA-A*02 protein). Additionally, normal healthy cells that maintain HLA-A*02 expression and co-express CEA (eg, gut mucosal tissue) will not be targeted due to the blocker portion of the Tmod CAR T cell that acts as a self-regulated safety switch that protects normal tissue from damage. A2 Bio believes this will provide a therapeutic safety window compared to previous solid tumor targeting therapies. This hypothesis will be explored in the study.

Participants for this study must enroll and have their T cells collected (apheresis) in the pre-screening BASECAMP-1 study (NCT04981119). T cells are collected, processed and stored for each participant. Upon disease progression the participant may screen for this study (EVEREST-1) and the participant's T cells are then manufactured and infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-1 based on their own disease course.

STATUS: Active / Recruiting 

PI: Sandip Patel, MD

Contact Number: (858) 249-4020

Trial Sponsor: A2 Biotherapeutics, Inc.

Phase 1 Clinical Trial of Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer

This is a phase I study of an agonistic CD40 antibody (mitazalimab) injected intratumorally at the time of surgical IRE in patients with locally advanced pancreatic cancer. Intratumoral delivery has potential to be more effective than systemic (intravenous) delivery while decreasing the systemic side effects of immunotherapy. We hypothesize that local delivery of mitazalimab at the time of IRE in patients with locally advanced pancreatic cancer will be safe, augment the immune effects of IRE, and decrease the risk of recurrence.

Irreversible electroporation (IRE) is a form of non-thermal ablation (tissue destruction) that is being used to treat locally advanced pancreatic cancers. Locally advanced pancreatic cancers are tumors that have not spread (metastasized to distant locations) but cannot be surgically resected. There is evidence that IRE can help to generate anti-tumor immune responses by releasing tumor antigens in the setting of inflammation. CD40 is an immune receptor that helps to stimulate antigen presentation to the immune system. Preclinical data from the PI's laboratory have shown that combination of IRE with an antibody that stimulates the CD40 receptor improves responses to IRE and inhibits metastatic tumor growth.

This is a phase I study of an agonistic CD40 antibody (mitazalimab) injected intratumorally at the time of surgical IRE in patients with locally advanced pancreatic cancer. Intratumoral delivery has potential to be more effective than systemic (intravenous) delivery while decreasing the systemic side effects of immunotherapy. We hypothesize that local delivery of mitazalimab at the time of IRE in patients with locally advanced pancreatic cancer will be safe, augment the immune effects of IRE, and decrease the risk of recurrence.

STATUS: Active / Recruiting 

PI: Rebecca White, MD

Contact Number: (858) 249-4020

Trial Sponsor: UCSD

A Phase 1 Basket Study Evaluating the Safety and Feasibility of T-Plex, Autologous Customized T Cell Receptor-Engineered T Cells Targeting Multiple Peptide/HLA Antigens in Participants With Antigen-positive Locally Advanced (Unresectable) or Metastatic Solid Tumors

TScan Therapeutics is developing cellular therapies across multiple solid tumors in which autologous participant-derived T cells are engineered to express a T cell receptor that recognizes cancer-associated antigens presented on specific Human Leukocyte Antigen (HLA) molecules.

This is a multi-center, non-randomized, multi-arm, open-label, basket study evaluating the safety and preliminary efficacy of single and repeat dose regimens of TCR'Ts as monotherapies and as T-Plex combinations after lymphodepleting chemotherapy in participants with locally advanced, metastatic solid tumors disease.

Participants will be screened in a separate screening study, TSCAN-003 (NCT05812027), to assess their HLA type, tumor-associated antigen (TAA) expression and loss of heterozygosity (LOH) status. The results of these tests will be used to determine initial eligibility in this study.

Depending on the genetic type, participants will be assigned to one of the following study groups:

Monotherapy:

• COHORT A: TSC-204-A0201 targeting MAGE-A1 on HLA-A*02:01
• COHORT B: TSC-204-C0702 targeting MAGE-A1 on HLA-C*07:02
• COHORT C: TSC-200-A0201 targeting HPV16 E7 on HLA-A*02:01
• COHORT D: TSC-203-A0201 targeting PRAME on HLA-A*02:01
• COHORT E: TSC-204-A0101 targeting MAGE-A1 on HLA-A*01:01
• COHORT F: TSC-201-B0702 targeting MAGE-C2 on HLA-B*07:02

T-Plex Combination:

• COHORT AB: TSC-204-A0201 + TSC-204-C0702
• COHORT AC: TSC-204-A0201 + TSC-200-A0201
• COHORT AD: TSC-204-A0201 + TSC-203-A0201
• COHORT AE: TSC-204-A0201 + TSC-204-A0101
• COHORT AF: TSC-204-A0201 + TSC-201-B0702
• COHORT BC: TSC-204-C0702 + TSC-200-A0201
• COHORT BD: TSC-204-C0702 + TSC-203-A0201
• COHORT BE: TSC-204-C0702 + TSC-204-A0101
• COHORT BF: TSC-204-C0702 + TSC-201-B0702
• COHORT CD: TSC-200-A0201 + TSC-203-A0201
• COHORT CE: TSC-200-A0201 + TSC-204-A0101
• COHORT CF: TSC-200-A0201 + TSC-201-B0702
• COHORT DE: TSC-203-A0201 + TSC-204-A0101
• COHORT DF: TSC-203-A0201 + TSC-201-B0702
• COHORT EF: TSC-204-A0101 + TSC-201-B0702

Participants will undergo leukapheresis to collect cells to manufacture the TCR-T products. They will then undergo lymphodepletion and receive one or two doses of the TCR-T cell therapy product as a monotherapy or part of a combination of TCR-Ts (referred to as T-Plex combinations in this study).

STATUS: Active / Recruiting 

PI: Sandip Patel, MD

Contact Number: (858) 249-4020

Trial Sponsor: TScan Therapeutics

First-in-Human, Phase I, Open-label, Multicenter, Dose Escalation Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of FL115 Monotherapy in Patients With Locally Advanced/Metastatic Solid Tumors

First-in-Human, Phase I, open-label, multicenter, dose-escalation study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of FL115 in patients with advanced solid tumors who have progressed or are intolerant to current standard-of-care therapies, including immune check-point inhibitors administered in single-agent or combination use.

This is a First-in-Human, Phase I, open-label, multicenter, dose-escalation clinical study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of FL115 when administered IV to adult patients with locally advanced/metastatic solid tumors who have progressed on, cannot tolerate, or do not have a standard-of-care therapy. If a patient is intolerant to standard-of-care therapy, the reason that the treatment could not be tolerated will be documented in the electronic case report form (eCRF). Patients will receive the investigational drug FL115 on Days 1, 8, 15, and 22 of Cycle 1 for the observation of AEs/SAEs to assess dose-limiting toxicity (DLT) in first 28 days. FL115 will be administered IV QW (on Days 1, 8, 15, and 22) in Cycle 2 and beyond. All patients will be monitored in the clinic over 24-hours for the C1D1 dose for monitoring potential cytokine release syndrome (CRS). If no CRS symptoms are observed after first dose, patients will not be asked for 24-hour inpatient monitoring for future injections (i.e. 2nd, 3rd and 4th dosing) based on the investigator discretion.

Seven dosing cohorts are planned, with doses of 3, 10, 30, 60, 120, 180 and 240 µg/kg.

For ethical reasons, the first 2 dose cohorts (3 and 10 µg/kg) are planned to enroll 1 patient per cohort because these 2 doses are considered suboptimal treatment for late-stage cancer patients. The first 2 dose level cohorts will each enroll 1 patient using an accelerated titration dose escalation design. If no DLT is observed by the end of the first cycle (28 days) of treatment, the dose will be escalated to the next dose cohort. However, if 1 treatment-related National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) or American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading ≥ Grade 2 toxicity occurs in the safety evaluation window, the study will be converted to a 3 + 3 design. After the initial 2 cohorts are completed, the study will use modified Fibonacci 3 + 3 dose-escalation design.

STATUS: Active / Recruiting 

PI: Sandip Patel, MD

Contact Number: (858) 249-4020

Trial Sponsor: Suzhou Forlong Biotechnology Co, Ltd.

Phase 1/2a Dose Escalation Study of ANPD001 in Sporadic Parkinson Disease

This clinical trial is designed to test the safety and tolerability of injecting ANPD001 cells that will mature into dopamine-producing cells into the brain of participants with Parkinson Disease. All participants will have ANPD001 cells manufactured from their own previously collected cells.

Participants will undergo a surgical implantation of cells that will mature into dopamine-producing neurons under general anesthesia into a part of the brain where dopamine production is decreased in patients with Parkinson Disease. The effect on Parkinson Disease symptoms, safety and tolerability, and cell survival are assessed for 5 years post-transplant (with MRI and PET imaging scans of the brain). Safety and tolerability are assessed annually for an additional 10 years via telephone call (total follow-up of 15 years).

STATUS: Active / Recruiting 

PI: Sharona Ben-Haim, MD

Contact Number: (858) 249-4020

Trial Sponsor: Aspen Neuroscience