Hotspot TCR-T study of gene-engineered adoptive cell therapy for incurable cancers

Hotspot TCR-T study of gene-engineered adoptive cell therapy for incurable cancers

Update October 2023: No additional patients will be enrolled to this study. We hope to open more adoptive cellular therapy clinical trials in the future. More information will be posted as it becomes available.

Update July 2023: Patient accrual has been completed for the Hotspot TCR-T study.

Update September 2022: Participation in the Hotspot TCR-T study is limited to 24 patients from the United States. The study is not accepting international patients at this time. Eligible patients who meet the screening criteria will be placed on a waiting list. There is currently a waiting period of six to twelve months before patients who meet the HLA and KRAS matching criteria are consented and screened for the study.

Earle A. Chiles Research Institute is among a limited number of centers in the world capable of developing and administering adoptive cell therapy, a highly personalized type of immunotherapy. We are recruiting U.S. adult patients with certain solid cancers for a phase I clinical trial to evaluate the safety and effectiveness of gene-engineered, adoptively transferred T cells.

T cells are a type of immune cell which, under the right circumstances, can recognize and attack cancer cells. T-cell transfer therapy is a form of adoptive cell therapy that enhances T cells in a laboratory so they can find and destroy cancer cells more effectively. While T-cell transfer therapy has been successful in treating some blood cancers, many solid cancers do not respond and continue to grow.  

Our researchers are studying whether T-cell transfer therapy and genetic engineering can shrink solid cancers that are resistant to therapy. In their landmark New England Journal of Medicine article Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer, Rom Leidner, M.D., Eric Tran, Ph.D., and Providence colleagues provide the world’s first report of metastatic pancreatic cancer regression through T-cell transfer therapy with genetically-engineered T cells.  

Drs. Tran and Leidner have opened a phase 1 clinical trial to evaluate this therapy in a small group of patients with solid cancers that are unresponsive to standard care. 

Targeting KRAS hotspot for incurable epithelial cancers 

Epithelial cancers are carcinomas that originate in the epithelial tissue found in the skin and organs throughout the body. They account for a broad array of the most common solid cancers – including breast, colon and lung – and are responsible for 85% of annual cancer deaths. 

In this study known as Hotspot TCR-T, T cells from patients are genetically engineered to express a T-cell receptor (TCR) that redirects the T cells to target a common cancer mutation called a hotspot. One such hotspot is a mutated form of the KRAS oncogene.  

In healthy cells, the KRAS protein supports normal cell growth and proliferation. Mutated KRAS variants result in uncontrolled cell growth and are present in 30% of epithelial cancers.  

Triple combination therapy 

To develop this therapy, T cells are obtained from a patient’s blood. In our Adoptive Cell Therapy Lab, the T cells undergo TCR gene-engineering to target hotspot mutations expressed by the patient’s cancer. Then they are amplified in magnitude and potency, and returned to the patient through intravenous infusion. This therapy is experimental. 

Patients enrolled in the study will also receive two additional immunotherapy agents that may enhance the activity and effectiveness of the transferred T cells: pembrolizumab and CDX-1140.  

This investigator-initiated study is led by Rom Leidner, M.D., medical director, Providence Head and Neck Cancer Program, and Eric Tran, Ph.D., assistant member and leader of the Adoptive Cell Therapy Lab at the Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon.

Providence Portland Medical Center in Portland, Oregon, is the only location to offer the study.

Get the full details here:   

Hotspot TCR-T: A Phase I/Ib Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T) Targeting Tumor-Specific Neoantigens, with in Vivo CD40 Activation and PD-1 Blockade, for Patients with Incurable Cancers 


Up to 24 U.S. patients will be enrolled to the study. Patients with metastatic or locoregionally advanced epithelial cancers which are considered incurable (have failed prior treatments or are not candidates for surgery) may be eligible.  

These include certain cancers of the breast, gastrointestinal tract (colon, stomach, gallbladder, bile ducts, pancreas and liver), lung, prostate and bladder. Patients with melanoma or cancers of the blood, soft tissue (sarcomas) or neurological tissue are not eligible. 

To qualify, participants must meet several eligibility criteria, including the following KRAS mutations and human leukocyte antigen (HLA) typing:

  • KRAS G12V with HLA-A*11:01 or HLA-DRB1*07:01 

  • KRAS G12D with HLA-A*11:01 or HLA-C*08:02 

To help determine patient eligibility, oncologists can coordinate two required, pre-screening tests:  

  1. Tumor next-generation sequencing (NGS) looking for KRAS G12D or KRAS G12V mutation. If the test is positive for KRAS, proceed to step 2 for HLA typing.
  2. High Resolution HLA Typing. For KRAS G12V, order HLA Typing A and DRB1. For KRAS G12D, order HLA Typing A and C. Note: Intermediate Resolution is not sufficient. 

One lab that offers high resolution HLA typing is Kashi Clinical Laboratories. It offers both physician ordering and direct patient ordering by phone. Call (877) 879-1815 to request the High Resolution Combination A, C, DRB1.

The cost of these tests is not covered by the Hotspot TCR-T research study and will be the responsibility of the patient or their insurance. 

There is approximately a 10% chance of meeting the HLA typing criteria. For those patients who do meet the KRAS and HLA screening criteria, we anticipate a waiting period of six to twelve months before eligible patients are enrolled to the study.

For these reasons, it is important for patients to contact their oncologist regarding their KRAS and HLA statuses. Patients and their oncologists should discuss the costs and appropriate time for testing and to evaluate other treatment options if there is not a match.

Oncology referral information 

Patients must have their NGS testing and HLA typing completed before being referred to the Clinical Research team at Providence Cancer Institute. We are not accepting Hotspot TCR-T study referrals through our oncology clinics.

For patients whose NGS testing and HLA typing match the requirements listed above, oncologists can contact our Clinical Research team by phone or email:

We are receiving a high volume of inquiries and responses may be delayed.  

Related resources

Immunotherapy at Providence 

Novel immunotherapy for pancreatic cancer employed by Providence researchers featured in New England Journal of Medicine

The National Cancer Institute (NCI) offers T-cell transfer clinical trials. Here is a listing NCI studies that are similar to the Providence Hotspot TCR-T study:

A study for people with GI cancers and two studies for people with advanced and early-stage lung cancer hope to develop better treatment options with the help of immunotherapy.
JACC earned re-accreditation for stem cell therapy treatment program.
Providence researchers say comprehensive genomic profiling can be pivotal in identifying gene mutations in a patient and tailoring personalized treatment strategies.
SITC 2023 provides a glimpse into scientific advances and breakthroughs in cancer immunotherapy by researchers from around the world.