Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Sarcoma

Pancreatic Cancer

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Antimetabolites

In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine.

In Part 1 (dose escalation), participants with sarcoma indications (regardless of AXL gene amplification status), non-small-cell lung cancer (NSCLC) (regardless of AXL gene amplification status), and solid tumors with AXL gene amplification, will receive ADCT-601 monotherapy.

In Part 2 (dose expansion), participants with selected sarcoma indications will receive ADCT-601 in combination with gemcitabine.

Participants will be split into 3 cohorts:

Cohorts 5 and 6: Sarcoma indications.

Cohort 7: Pancreatic cancer.

In Part 2 (dose expansion), participants with a selected indication will receive ADCT-601 monotherapy.

Participants will be split into cohorts:

Cohort 1: Soft tissue sarcoma (STS).

Cohort 2: Pancreatic adenocarcinoma (PAAD).

Cohort 3: NSCLC.

Cohort 4: Solid tumors with known AXL expression.

ADCT-601

Contact ADC Therapeutics

The primary objective of this study is to identify the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD), and characterize the safety and tolerability of ADCT-601 monotherapy and in combination with gemcitabine.

A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors

A Phase 1b, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Mipasetamab Uzoptirine (ADCT-601) Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Selected Advanced Solid Tumors

Adverse events (AEs) and serious adverse events (SAEs) are defined as any untoward medical occurrence in participants whether or not considered related to the investigational medicinal product. Any clinically significant changes in vital signs, laboratory values, 12-lead electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status results will be recorded as AEs and SAEs.

ADC Therapeutics S.A.

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Head and Neck Neoplasms

Carcinoma, Renal Cell

Lung Neoplasms

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles

MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water.

MGCD516

Richard Chao, MD

MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles.

During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations.

Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled.

During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed.

During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon the following cancer diagnosis:

Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL.

Head and neck squamous cell carcinoma with genetic alterations in MET.

Clear cell renal cell carcinoma refractory to angiogenesis inhibitors.

Metastatic prostate cancer with bone metastases.

Other cancer diagnosis having a selected genetic alteration in MGCD516 target RTKs.

Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer

A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies

Proteins include VEGF A, soluble VEGF-R2 and soluble MET

Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Mirati Therapeutics Inc.

Symptoms and General Pathology

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Testicular Neoplasms

Endometrial Neoplasms

Endocrine Gland Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Uterine Neoplasms

Uterine Diseases

Genital Neoplasms, Male

Genital Diseases, Male

Male Urogenital Diseases

Testicular Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Anticonvulsants

Vitamins

Antibodies

Niacinamide

Niacin

Nicotinic Acids

Cannabidiol

Immunoglobulins

Nicotinamide

Nicotinic Acid

Vitamin B3

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell therapy group.

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the IL7/CCL19 secreting CAR-NK cell therapy group.

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group.

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus CBD therapy group.

Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus NAD therapy group.

Engineering Claudin6, GPC3, Mesothelin, or AXL targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Lag3 secreting vector into NK cells, which are isolated from patients with advanced ovarian cancer or other cancers with expression of Claudin6, GPC3, Mesothelin, or AXL, and then transfusing them back the patients.

In some cases, the CAR-NK cells will be combined with CBD or NAD to enhance the therapeutic efficacy.

Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells

Zhenfeng Zhang, MD, PHD

Bingjia He, MD

This study is an open, exploratory clinical study to evaluate the safety and preliminary efficacy of Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells in patients with Claudin6, GPC3, Mesothelin, or AXL-positive advanced solid tumors (ovarian cancer and others)

1. Choose appropriate advanced cancer patients with Claudin6, GPC3, Mesothelin, or AXL expression, with written consent for the study;
2. Perform PBMCs apheresis from the patient and isolate NK cells, transfect the NK cells with Claudin6, GPC3, Mesothelin, or AXL targeting CAR, amplify the number of transfected NK cells as needed, test the quality and killing activity of the Claudin6, GPC3, Mesothelin, or AXL-CAR-NK cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
3. To enhance the killing capability, some CAR-NK cells are genetically engineered to express and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Lag3; some CAR-NK cells are combined with Cannabidiol(CBD) or Nicotinamide adenine dinucleotide (NAD);
4. Evaluate the clinical results as needed.
5. Will also perform the similar clinical trial on different cancer types with Claudin6, GPC3, Mesothelin, or AXL expression.

CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors

Phase I Trial to Evaluate Safety and Preliminary Efficacy of CLDN6/GPC3/Mesothelin/AXL-CAR-NK in Patients With CLDN6/GPC3/Mesothelin/AXL-positive Advanced Solid Tumors

The type, frequency, severity, and duration of adverse events as a result of Claudin6, GPC3, Mesothelin, or AXL- CAR-NK cells infusion will be summarized.

Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response, prior to progression or further anti-cancer therapy.

Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, SD assessed at least 6 weeks after the first dose) is observed as best overall response.

Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1/recurrence) or death from any cause, whichever occurs first.

Second Affiliated Hospital of Guangzhou Medical University

Adenocarcinoma

Neoplastic Cells, Circulating

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Neoplasm Metastasis

Neoplastic Processes

Gastrointestinal Agents

Pancrelipase

Pancreatin

Newly diagnosed major patients with metastatic pancreatic cancer, naïve of any treatment for metastatic disease

Detection of CTC-AXL(+) using 2 techniques:

* CellSearch®, FDA-USA approved technology
* EPIDROP System

CellSearch® (Menarini Company) The current gold-standard CellSearch® technique requires the use of CellSave tubes. This technique allows the isolation of fixed CTCs. This technique uses a positive (CellSearch® Epithelial Cell Kit) enrichment method from total blood using magnetic beads coupled to an EpCAM capture antibody. CTCs are then detected (anti-panCK antibodies, DAPI, anti-CD45 and characterized (anti-AXL antibody) by immunofluorescence (IF).

EPIDROP It requires the use of EDTA tubes. This technique is based on a method of negative enrichment of CTCs from total blood using a cocktail of tetrameric antibodies to eliminate unwanted blood cells and to preserve only purified tumor cells (RosetteSep - StemCell Technology).Then, cells are loaded in a microfluidic chip. The detection and characterization is done by IF to the single cell in micro-droplets.

Detection of circulating tumor cells expressing Axl: CTC-AXL(+)

Thomas Bardol, MD

Sarah Girot

Catherine Alix-Panabières, PhD

In solid cancers, some more aggressive tumor cells actively detach from the primary lesion and then travel through the circulating compartment to reach distant organs and form micro-metastases. These circulating tumor cells (CTCs) that have become disseminated tumor cells (DTCs) flourish in their new environments and may remain dormant for many years after the complete resection of the primary tumor. Detecting CTCs in the blood is also relevant for assessing tumor progression, prognosis and therapeutic follow-up. The non-invasive, highly sensitive for CTCs analysis is called "liquid biopsy". Pancreatic adenocarcinoma and breast cancer remain among cancers of very poor prognosis and thus represent a major therapeutic challenge. In recent years, the Axl membrane tyrosine kinase receptor has been the target of growing interest. Activation of the Gas6/Axl signaling pathway is associated with, among other things, tumor cell growth and survival, epithelial to mesenchymal transition (EMT) or drug resistances. In addition, Axl overexpression is frequently identified in patients with pancreatic adenocarcinoma and is associated with a poor prognosis. For example, the Laboratoire des Cellules Circulantes Rares Humaines (LCCRH) at the CHU and the University of Montpellier has developed two new "CTC-AXL" tests to detect CTCs expressing Axl: one using the CellSearch® (gold standard and FDA-approved) system and the other using the EPIDROP technique. The purpose of this research project is to assess the concordance of the "CTC-AXL" measurement by the innovative EPIDROP technique and the CellSearch® technique in patients with metastatic pancreatic or breast cancer.

In solid cancers, after the formation and growth of the primary tumor, some more aggressive tumor cells actively detach from it and then travel through the circulating compartment to reach distant organs (bone marrow - liver - lung - brain...) and constitute new foci or micro-metastases. These circulating tumor cells (CTCs) that have become disseminated tumor cells (DTCs) flourish in their new environments and may remain dormant for many years after the complete resection of the primary tumor. Due to events not fully elucidated, DTCs can develop on site giving rise to macroscopic metastases but also join again the circulating compartment in the form of CTCs, swarm, colonize other organs and cause secondary metastases.

Detecting CTCs in the blood is very relevant for assessing tumor progression but also promising in terms of cancer disease prognosis and therapeutic follow-up. This new approach, published for the first time in 2010 under the term liquid biopsy, is therefore defined as a non-invasive blood test, extremely sensitive, achievable in real time and that allows the analysis of CTCs.

Currently, the choice of targeted therapies for a given patient is made after analyzing the primary tumor for expression and/or genomic status of specific molecular targets.

Many studies show that metastatic cells have phenotypic and genotypic characteristics distinct from those of most of the primary tumor. This can be explained either because metastatic cells acquire new genomic skills over time, or because a subset of metastatic sub-clone pre-exists within the primary tumor but has escaped detection by standard tissue biopsy techniques.

A direct analysis of CTCs could provide important additional information to prevent patients from inappropriate, costly treatments and harmful side effects.

For several years, the AXL protein, a tyrosine kinase receptor, has emerged as a new strategic target in oncology. Over-expression of AXL has been frequently identified in patients with pancreatic adenocarcinoma. AXL is a member of the Tyro3-Axl-Mer family, like its ligand protein Gas-6 (growth arrest-specific). An activation of the Gas6/AXL signaling pathway results in the activation of several effector pathways such as RAS/RAF/MEK/ERK or PI3K/AKT and is associated with, among other things, tumor cell growth and survival, metastatic formation and dissemination, Epithelial-to-mesenchymal transition (EMT) or drug resistances. It has been shown clinically that the AXL protein is a factor of poor prognosis and resistance to reference treatments (radiotherapy, chemotherapy or targeted therapy). Thus, many therapeutic strategies have been proposed and developed to inhibit the AXL pathway, ranging from chemical molecules, blocking its kinase activity and therefore the underlying signaling pathways, to nucleotide aptamers, AXL fusion proteins, and monoclonal antibodies.

Pancreatic adenocarcinoma, the 4th leading of cancer related deaths, remains among cancers of very poor prognosis and thus represents a major therapeutic challenge. The median overall survival is 11.1 months after optimal treatment (FOLFIRINOX). The clinical relevance and oncogenic potential of AXL in the progression of different types of tumors have been largely evidenced. Indeed, 50% to 75% of pancreatic adenocarcinoma samples have overexpression of AXL and the level of expression of AXL is correlated with clinical parameters indicating tumor aggressiveness and poor prognosis such as frequency of distant metastases or the survival.

In this context, the LCCRH lab, which has specialized in the detection and analysis of CTCs for 20 years, has developed a CTC-AXL detection test using the CellSearch® system. The CellSearch® system is the only method approved by the Food and Drug Administration (FDA) for the detection of CTC in colorectal, breast and metastatic prostate cancers. In addition, the LCCRH holds a patent for another technology for the detection and characterization of live and functional CTCs, called EPIDROP. The implementation of the AXL research is already done for AXL labelling on CTCs in EPIDROP as well as the visualization of the AXL cleavage by live CTC.

Thanks to this unique functional test of CTCs, it is easy to imagine offering an oncology 'oncogram' by testing in real time the effectiveness of drugs on CTCs and personalized medicine to patients.

This real-time liquid biopsy proposal on functional CTCs is quite innovative in Oncology.

To date, there are no studies on the study of functional CTCs related to AXL.

Primary objective:

- Evaluate the concordance of the CTC-AXL measurement (inclusive) by the innovative EPIDROP technique and the CellSearch technique®

Secondary objectives:

* Evaluate the accuracy of the CTC-AXL measurement (inclusive) between EPIDROP and CellSearch®
* Assess the degree of agreement between CTC-AXL measurement (inclusive) by EPIDROP and CellSearch®
* Evaluate the overall survival of patients with metastatic pancreatic cancer based on the number of circulating tumour cells carrying the AXL marker measured by EPIDROP or CellSearch® at inclusion
* Evaluate the progression-free survival of patients with metastatic pancreatic cancer based on the number of circulating tumour cells carrying the AXL marker measured by EPIDROP or CellSearch® at inclusion
* Culture CTCs from the blood sample (EDTA 10mL)
* Creation of a single liquid biopsy bio-bank for pancreatic cancer involving only plasma storage

  * Study the expression of PD-L1 (at inclusion) and detect the CTC subgroup expressing PD-L1 using EPIDROP and CellSearch® techniques;
  * Study the circulating immune system in this cohort of patients with metastatic pancreatic cancer by performing immunological analysis on blood mononuclear cells;
  * Determine if there is a significant correlation between the detection of CTC and CTC-PD-L1 and the circulating immune system (T cells, NK cells, B cells, macrophages, immune checkpoints, platelets);
  * To assess the correlation between CTC, CTC-PD-L1 and immune cells and the clinical outcomes (progression-free survival, overall survival) of these patients with metastatic pancreatic cancer.

Single-centre prospective cohort Cohort of newly diagnosed major patients with metastatic pancreatic cancer, naïve of any treatment

Liquid Biopsy and Pancreas Cancer: Detection of AXL(+) CTCs (CTC-AXL-PANC)

Liquid Biopsy and Pancreas Cancer: Detection of AXL(+) Functional CTCs Using EPIDROP

CTC-AXL measurement concordance rate by EPIDROP (AXL(-): 0 vs AXL(+): 1) and CellSearch® (AXL(-): 0 vs AXL(+): 1)

Overall survival defined by the time between the date of diagnosis of the metastatic disease and the date of death regardless of the cause

Progression-free survival defined by the time between the date of diagnosis of the metastatic disease and the date of the 1st progression or the date of death regardless of the cause

Number of CTC labelled by anti-PD-L1 antibody detected by EPIDROP®

Number of CTC labelled by anti-PD-L1 antibody detected by CellSearch

University Hospital, Montpellier

Blood and Lymph Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

Carcinoma, Squamous Cell

Lymphoma

Melanoma

Microsatellite Instability

Carcinoma, Transitional Cell

Hodgkin Disease

Lymphosarcoma

Transitional Cell Carcinoma

Hodgkin Lymphoma

Patients will receive continuous daily oral doses of RXDX-106 in 21 day cycles. To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), study drug will be administered in an escalated fashion starting at dose of 10 mg/day and will proceed at the dose levels prespecified by the dose escalation schema. Once daily dosing for RXDX-106 will initially be tested. However, other dosing schedules (eg, every other day, weight based, etc) may be tested based on safety and PK data to optimize drug exposure.

RXDX-106

Pratik S. Multani, MD, MS

Sandra Pierina D'Angelo, MD

This is a first-in-human, open label, multicenter, dose escalation study of RXDX-106 in patients with locally advanced or metastatic solid tumors, who have no available therapy likely to convey clinical benefit.

This study will examine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary efficacy of RXDX 106.

The primary objective of Phase 1 is to assess safety and tolerability, determine the recommended phase 2 dose (RP2D) and assess the pharmacokinetics of RXDX-106. The secondary objective is to evaluate the preliminary antitumor activity of RXDX-106, as assessed by objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and Immune Response Related Criteria in Solid Tumors (iRECIST) in patients with advanced or metastatic solid tumors.

The proposed starting dose of RXDX-106 was calculated based upon nonclinical toxicology studies to determine a recommended first-in-human starting dose, which may be below the biologically active level. Therefore, in order to minimize the number of patients treated at this dose, an accelerated titration design will be used for the first cohort, after which, a conventional 3+3 scheme will be followed for enrollment in subsequent dose levels.

Final determination of the single agent RP2D will be based on available safety, tolerability, PK, pharmacodynamics, and efficacy data from different dose levels and schedules tested, but will be no higher than the maximum tolerated dose. After RP2D has been determined, additional expansion cohorts of patients (up to 15) with specific tumor types, treatment history, and/or expression of a specific biomarker may be enrolled.

Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors

A Study of RXDX-106, an Oral Immunomodulatory TYRO3, AXL, and MER (TAM) Tyrosine Kinase Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors

Determine dose-limiting toxicities of RXDX-106

Radiographic measurement per RECIST v1.1 and iRECIST as assessed by Investigator

Per RECIST v1.1 and iRECIST as assessed by Investigator

Hoffmann-La Roche

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

The safety and efficacy of CCT301-59 will be evaluated for subjects with ROR2 positive biopsy in a standard 3+3 dose escalation approach. 3 CAR T dosage will be tested in this study: 1×10\^5/kg, 1×10\^6/kg, 1×10\^7/kg CAR+ T cells.

The safety and efficacy of CCT301-38 will be evaluated for subjects with AXL positive but ROR2 negative biopsy in a standard 3+3 dose escalation approach. 3 CAR T dosage will be tested in this study: 1×10\^5/kg, 1×10\^6/kg, 1×10\^7/kg CAR+ T cells.

Subjects will undergo blood draw to isolate peripheral blood mononuclear cells (PBMCs) for the production of CCT301-38. During CCT301-38 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocyte depletion. After lymphodepletion, subjects will receive one dose treatment with CCT301-38 by intravenous (IV) injection.

CCT301-38

Subjects will undergo blood draw to isolate peripheral blood mononuclear cells (PBMCs) for the production of CCT301-59. During CCT301-59 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocyte depletion. After lymphodepletion, subjects will receive one dose treatment with CCT301-59 by intravenous (IV) injection.

CCT301-59

Tongyu Zhu

This is a two arm, open-label, dose escalation and dose expansion clinical study to evaluate the safety and efficacy of infusion of autologous CCT301-38 or CCT 301-59 T cells in adult subjects with relapsed and refractory stage IV metastatic renal cell carcinoma.Subjects with ROR2 positive biopsy will receive CCT301-59. Subjects with AXL positive biopsy that are ROR2 negative will receive CCT301-38.

Subjects with ROR2 positive biopsy will receive CCT301-59. Subjects with AXL positive biopsy that are ROR2 negative will receive CCT301-38.

Safety and Efficacy of CCT301 CAR-T in Adult Subjects With Recurrent or Refractory Stage IV Renal Cell Carcinoma

A Dose Escalation and Dose Expansion Trial to Assess the Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) CCT 301-38 or CCT 301-59 in Patients With Recurrent or Refractory Stage IV Renal Cell Carcinoma

Incidence of adverse events defined as dose-limiting toxicities (DLT)

Objective Response Rate of confirmed complete and partial remission by independent radiology review RECIST (1.1)

Shanghai Public Health Clinical Center

Shanghai PerHum Therapeutics Co., Ltd.

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Camurati-Engelmann Disease

Immunomodulating Agents

Patients will receive 3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1x10e6/kg-10x10e6/kg weight.

CAR-T cells injection: (1-10×10e6/kg CAR-T for each treatment; 3 or more cycles.

CAR-T cells targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR

Zhenfeng Zhang, MD,PhD

Peng Li, PhD

Xianhong Xiang, MD,PHD

Yonghui Huang, MD,PHD

Deji Chen, MD,PhD

The third generation of CAR-T cells that target GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function of the these individual or combination of the CAR-T cells for immunotherapy of human cancer patients with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR

-CAR-T cell immunotherapy on human cancers will firstly be tested.

1. Choose appropriate patients with advanced lung or other cancers,with written consent for this study;
2. Perform biopsy to determine the expression of HER2, Mesothelin, Lewis-Y, PSCA, MUC1, GPC3, AXL, EGFR, Claudin18.2, or B7-H3 of the tumor by western blotting or IHC;
3. Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed;
4. To enhance the killing capability, CD4+ T cells are genetically engineered to express TGFβ-CAR and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Tigit; CD8+T cells are constructed to express GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR

   -DAP10-CAR with knockdown of PD1/HPK1;
5. Other cancers with these cell surface antigen expressions are also recruited if needed;
6. Evaluate the clinical results as needed.

Use engineered CAR-T cells to kill cancer cells with certain targets.

GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers

CAR-T Targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR for Immunotherapy of Lung Cancer: Phase I Clinical Trial

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors	NCT05389462	Advanced Solid ...	ADCT-601 Gemcitabine	18 Years -	ADC Therapeutics S.A.
Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer	NCT02219711	Advanced Cancer	MGCD516	18 Years -	Mirati Therapeutics Inc.
CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors	NCT05410717	Stage IV Ovaria... Testis Cancer, ... Endometrial Can... CAR NK	Claudin6, GPC3,...	18 Years - 75 Years	Second Affiliated Hospital of Guangzhou Medical University
Liquid Biopsy and Pancreas Cancer: Detection of AXL(+) CTCs (CTC-AXL-PANC)	NCT05346536	Pancreatic Duct... Metastatic Panc... Circulating Tum...	Detection of ci...	18 Years -	University Hospital, Montpellier
A Study of Mipasetamab Uzoptirine (ADCT-601) in Participants With Solid Tumors	NCT05389462	Advanced Solid ...	ADCT-601 Gemcitabine	18 Years -	ADC Therapeutics S.A.
Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors	NCT03454243	Advanced or Met...	RXDX-106	18 Years -	Hoffmann-La Roche
Safety and Efficacy of CCT301 CAR-T in Adult Subjects With Recurrent or Refractory Stage IV Renal Cell Carcinoma	NCT03393936	Renal Cell Carc...	CCT301-38 CCT301-59	18 Years - 70 Years	Shanghai PerHum Therapeutics Co., Ltd.
Safety and Efficacy of CCT301 CAR-T in Adult Subjects With Recurrent or Refractory Stage IV Renal Cell Carcinoma	NCT03393936	Renal Cell Carc...	CCT301-38 CCT301-59	18 Years - 70 Years	Shanghai PerHum Therapeutics Co., Ltd.
Liquid Biopsy and Pancreas Cancer: Detection of AXL(+) CTCs (CTC-AXL-PANC)	NCT05346536	Pancreatic Duct... Metastatic Panc... Circulating Tum...	Detection of ci...	18 Years -	University Hospital, Montpellier
GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR-CAR-T Cells Against Cancers	NCT03198052	Lung Cancer Cancer Immunotherapy CAR-T Cell	CAR-T cells tar...	18 Years - 75 Years	Second Affiliated Hospital of Guangzhou Medical University
Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors	NCT03454243	Advanced or Met...	RXDX-106	18 Years -	Hoffmann-La Roche

Spots Global Cancer Trial Database for axl

Every month we try and update this database with for axl 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 axl

Every month we try and update this database with for axl 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 axl 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.