CAR-T clinical trials for Neuroendocrine Cancer (plus bonus section on CAR-NK)

Update 29th August 2025

Progress Seen in CDH17 CAR T Trial. Chimeric Therapeutics has reported that a neuroendocrine cancer patient in the Phase 1 clinical trial of CAR T cell therapy has experienced tumour shrinkage. In an update for investors on October 8, Chimeric reported 8 patients have been treated so far, with two more waiting for treatment. Two of the 8 have intestinal NETs. Read more here.

Update 4th June 2025

CAR T-Cell Therapy for Neuroendocrine Cancer, Now in Clinical Trial, Receives FDA FAST TRACK Designation. Read more here.

Update 17th October 2024

First patient dosed. Read more here.

Update October 31st, 2023

Chimeric Therapeutics, an Australian leader in cell therapy, announced today that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of CHM 2101, Chimeric’s first in class CDH17 CAR T cell therapy for gastrointestinal cancers. With the FDA IND clearance Chimeric will now begin the initiation of a phase 1 /2 multi-site clinical trial in patients with advanced Colorectal Cancer, Gastric Cancer and Neuroendocrine Tumours. The study is planned to begin patient enrolment in 2024 – see details of the trial below. See announcement – click here

This article indicates the preclinical in vivo trials look promising. Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues | Nature Cancer – Read more here

What is CAR-T?

CAR-T – chimeric antigen receptor T-cell – therapy is specifically developed for each individual patient and involves reprogramming the patient’s own immune system cells which are then used to target their cancer, i.e. it’s an immunotherapy. It is a highly complex and potentially risky treatment, but it has been shown in trials to cure some patients, even those with quite advanced cancers and where other available treatments have failed.

The treatment involves several steps over a number of weeks. First the patient’s blood is taken and is sent off to the manufacturer’s laboratory. Here the patient’s blood is ‘trained’ to fight the cancer cells. The CAR-T blood is then transported back to the hospital and the patient is administered with the CAR-T to treat their condition.

It has not been deployed in clinical trials for Neuroendocrine Neoplasms but leading CAR-T company Chimeric recently announced the expansion of their pipeline with the exclusive licensing of CHM 2101, a novel, 3rd generation CDH17 CAR T invented at the University of Pennsylvania. CHM 2101 (CDH17 CAR T) is currently in preclinical development with a planned phase 1 clinical trial in 2022 in Neuroendocrine Tumours, Colorectal, Pancreatic and Gastric Cancer.

ANNOUNCEMENT: CHIMERIC ACHIEVES FIRST MILESTONE ON THE PATH TO CDH17 CAR T CLINICAL TRIAL

● Phase 1 plasmid manufacturing commenced
● Phase 1 clinical trial for neuroendocrine & colorectal tumours planned for 2022
● Positions Chimeric to have a minimum of two Phase 1 trials underway during 2022

Chimeric Therapeutics (ASX:CHM, “Chimeric”), a clinical-stage cell therapy company and the ASX leader in cell therapy, is pleased to announce the successful completion of the manufacturing for CHM 2101 research-grade plasmids, a critical first step in the development of CDH17 CAR T. Manufacturing of CAR T therapies is dependent upon plasmids and viral vectors that hold the genetic instructions for each specific CAR T product. Plasmids are small DNA molecules that carry genetic instructions and their successful manufacture marks an important early step for all CAR T therapies.

In collaboration with the University of Pennsylvania, all of the research-grade helper and transfer plasmids for the CDH17 CAR T have been completed and released. The achievement of this first step in CAR T manufacturing enables progression to research vector manufacturing, GMP plasmid and vector manufacturing and advancement of technical operations in readiness for the CDH17 CAR T phase 1 clinical trial.

Chimeric’s CEO and Managing Director Jennifer Chow said: “We are very pleased that we have been able to achieve this key first step so rapidly after licensing. This accomplishment speaks to the commitment and drive that the Chimeric and University of Pennsylvania teams share to move this important CAR T forward to Phase 1 clinical trials.”

In addition to commencing the CDH17 CAR T Phase 1 trial in 2022, Chimeric is also progressing its CLTX CAR T Phase 1 clinical trial in glioblastoma (brain cancer) at The City of Hope Cancer Centre in California, where patients are now receiving second dose levels.

Interest point. The UK NHS is already using CAR-T for treating relapsed or refractory B-cell acute lymphoblastic leukaemia (ALL) in people up to the age of 25 years. A second one has been approved for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after 2 or more systemic therapies. Read here.

A more in-depth summary of CAT-T tech is given here.

A Phase 1/2 Study to Evaluate CHM-2101, an Autologous Cadherin 17 Chimeric Antigen Receptor (CAR) T Cell Therapy

Detailed Description:

This is a Phase 1/2 open-label study to evaluate CHM-2101, an autologous CDH17 CAR T-cell therapy for the treatment of advanced gastrointestinal (GI) cancers that are relapsed or refractory to at least 1 standard treatment regimen in the metastatic or locally advanced setting. The study has 2 parts: Phase 1, Dose Escalation and Expansion, and Phase 2.

Potential participants will provide written consent and be screened for study eligibility prior to undergoing any screening procedures, including leukapheresis. Protocol-specified criteria must be met prior to the start of leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). Eligible participants will undergo leukapheresis to collect PBMCs for product manufacturing, which comprises enrichment of T cells, lentiviral transduction, ex vivo expansion, and cryopreservation of the CHM-2101 cell product. Participants who have a leukapheresis or manufacturing failure may be permitted a second attempt at leukapheresis.

Bridging chemotherapy (treatment between the time of leukapheresis and first dose of lymphodepleting chemotherapy [LDC]) is permitted at the discretion of the investigator, if needed to maintain disease stability during CHM-2101 manufacturing time. Bridging chemotherapy is prohibited within the 2 weeks prior to leukapheresis and 2 weeks prior to planned CHM-2101 infusion.

Specific criteria to proceed should be reviewed prior to leukapheresis, LDC, and CHM-2101 infusion.

Participants will be followed in this study for 18 months or until disease progression.

Click the blue link below to see the clinical trials document:

A Phase 1/2 Study to Evaluate CHM-2101, an Autologous Cadherin 17 Chimeric Antigen Receptor (CAR) T Cell Therapy – Full Text View – ClinicalTrials.gov – (ClinicalTrials.gov ID: NCT06055439)

Gene Modified Immune Cells (IL13Ralpha2 CAR T Cells) After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma or Metastatic Solid Tumors

This is a phase 1 multiple cancer clinical trial taking place in UCLA California. The list includes Metastatic Malignant Solid Neoplasm (technically includes all Stage IV Neuroendocrine Neoplasms) but individual types mentioned below. Inclusion criteria indicates conditions must be ‘relapsed’ or ‘refractory’.

The list from clinical trials document.

Metastatic Malignant Solid NeoplasmMetastatic MelanomaPathologic Stage IIIC Cutaneous Melanoma AJCC v8Pathologic Stage IV Cutaneous Melanoma AJCC v8Recurrent Malignant Solid NeoplasmRefractory Malignant Solid NeoplasmUveal MelanomaAcral MelanomaNeuroendocrine TumorsParagangliomaPheochromocytomaAdrenocortical CarcinomaPancreatic Neuroendocrine TumorThyroid CancerBreast CancerLung AdenocarcinomaHead and Neck Squamous Cell Carcinoma

For more see the Net Research Foundation summary by clicking here.

CAR-T vs CAR-NK

Chimeric Antigen Receptor (CAR) immunotherapy has emerged as a promising approach for cancer treatment. In fact, having demonstrated substantial efficacy in pre-clinical and clinical studies, the U.S. Food and Drug Administration (FDA) has approved, to date, seven CAR-T cell therapies for the treatment of various hematologic cancers.. Despite this encouraging progress, CAR-T cell-based therapies face several challenges, including risk of severe side effects, such as cytokine release syndrome (CRS), neurotoxicity, and graft-versus-host disease (GvHD). By combining CAR specificity with NK (natural killer) cell natural cytotoxicity, CAR-NK cells may tackle some of the challenges faced by CAR-T cell therapies.

So what are the differences. CAR‑T and CAR‑NK differ in cell type, safety profile, manufacturing model, and suitability for solid tumours, and those differences matter a lot when thinking about hard‑to‑treat solid malignancies.

How the two platforms fundamentally differ

1) Cell biology and target recognition

CAR‑T cells come from the adaptive immune system and normally require MHC‑restricted antigen presentation. Tumours often evade this by down‑regulating MHC.
CAR‑NK cells come from the innate immune system and do not depend on MHC, allowing them to attack cells that have escaped T‑cell surveillance.

This is one of the reasons CAR‑NK is being explored for solid tumours, where immune evasion is common.

Safety and toxicity differences

2) Toxicity profile

CAR‑T can cause severe cytokine release syndrome (CRS) and ICANS neurotoxicity, sometimes life‑threatening.
CAR‑NK has a much lower risk of CRS and neurotoxicity because NK cells have a shorter lifespan and a different cytokine signature.

This is why CAR‑NK is considered potentially safer for frailer patients or those with heavy tumour burden.

Manufacturing and availability

3) Autologous vs off‑the‑shelf

CAR‑T is usually autologous: cells must be collected from the patient, engineered, expanded, and reinfused. This is slow and expensive.
CAR‑NK can be allogeneic from donors, cord blood, iPSCs, or NK cell lines, enabling off‑the‑shelf products.

This is a major advantage for aggressive cancers like pancreatic adenocarcinoma, where waiting weeks for manufacturing is often not feasible.

Persistence and durability

4) How long the cells last

CAR‑T cells can expand massively and persist for years, giving long‑term remission in blood cancers.
CAR‑NK cells persist for a shorter time, which reduces toxicity but may require repeat dosing or engineering to improve survival.

For solid tumours, shorter persistence may actually be beneficial if the tumour microenvironment is highly inflammatory.

Performance in solid tumours

5) Current evidence

CAR‑T has struggled in solid tumours due to poor trafficking, hostile microenvironment, and antigen heterogeneity.
CAR‑NK may overcome some of these barriers because NK cells naturally infiltrate stressed tissues and can kill without antigen presentation.

Summary of CAR-NK.

Early‑phase CAR‑NK trials in solid tumours (glioblastoma, ovarian, pancreatic preclinical models) show promising but still early signals but CAR-T is ahead in the clinical trials arena. Yes — CAR‑T is ahead of CAR‑NK today in approvals, evidence, and infrastructure. But — CAR‑NK is advancing quickly, and many researchers believe it may ultimately be more suitable for solid tumours, including NETs, because of its safety, off‑the‑shelf nature, and innate biology. Clinical trials for CAR-NK are sparse and the only CAR-NK worth mentioning is based in China. Click here. First check inclusion and exclusion criteria as there are many contraindications to being accepted. e.g. the only one mentioning Neuroendocrine Neoplasms is focused on DLL-3 positive cases.

Read this summary of CAR-NK – of dos Reis FD, Saidani Y, Martín-Rubio P, Sanz-Pamplona R, Stojanovic A and Correia MP (2025) CAR-NK cells: harnessing the power of natural killers for advanced cancer therapy. Front. Immunol. 16:1603757. doi: 10.3389/fimmu.2025.1603757

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General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net

The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.

Finally

Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product. Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document. Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET