Loxo Oncology has shared interim clinical data from an ongoing study of the drug LOXO-292. The study, a Phase 1/2 clinical trial, involves patients with RET-mutant medullary thyroid cancer, as well as patients who have RET fusion-positive thyroid cancer. To read about these results in more detail, you can view the source press release here, at Loxo’s website.

About Thyroid Cancer

Thyroid cancer is a rare form of cancer that affects the thyroid, a small gland at the bottom of the neck that’s involved in producing hormones. There are several types of thyroid cancer, one of which is medullary thyroid cancer (MTC, many patients in the study had a subset of this form). Some thyroid cancers are associated with genetic changes to RET kinase, and, according to Loxo’s announcement, ~60% of MTCs have activated RET point mutations.

About LOXO-292

LOXO-293 is an investigational drug that’s being researched as a possible treatment for cancers that involve changes to RET kinase, including a subset of patients with thyroid cancer. The drug is being tested in an ongoing phase 1/2 trial called Libretto-001. This study is made up of a Phase 1 escalating dose portion, and a Phase 2 expanding dose portion. Researchers are trying to determine the best or maximum dose, and will also look at safety, duration of response, and overall response rate.


The interim results are based on 38 patients, 29 of who have RET-mutant MTC, and 9 of who have RET fusion-positive thyroid cancer. All patients had been heavily pre-treated before the study, and, since joining the trial, had been followed up for a median duration of about eight and a half months.

The overall response rate for the patients with RET-mutant MTC was 56% (15 of the 29), two of which were complete responses and thirteen of which were partial responses. There are also two more patients who are thought to have achieved partial responses but are still awaiting confirmation from assessments.

Seven of the nine patients who have RET fusion-positive thyroid cancer have shown partial responses (78%), and one more patient may have tumour regression.

Thyroid Cancer

What is thyroid cancer?

Thyroid cancer starts in the thyroid, a gland at the base of the throat (below the Adam’s apple). The thyroid makes hormones that help control blood pressure, heart rate, body temperature, and weight.  Thyroid cancer is a mass of accumulated abnormal cells (tumors) found inside the thyroid that have grown out of control. Tumors occur when genes that regulate normal cell growth are mutated or damaged, which leads to cells growing and dividing at an overaccelerated, unregulated pace. Thyroid cancer tends to occur in more women than men. On average, about 14 new cases per 100,000 people appear per year in the United States. While some statistics indicate that thyroid cancer is one of the most rapidly increasing cancers in the U.S., this is largely because physicians have started using thyroid ultrasounds more, which has allowed them to find cases that would have been left undetected in the past.

What are the types of thyroid cancer?

Different types of cancer develop from the different kinds of cells in the thyroid. These can affect how serious the cancer is and how the cancer will be treated. Many tumors that grow in the thyroid gland are benign, which means they are non-cancerous and won’t spread, but some are malignant, which are cancerous and can spread to other body parts. Lumps or bumps in the thyroid are called thyroid nodules; most of these are benign, but they can sometimes be malignant. There are multiple types of thyroid cancer. The most common type is papillary thyroid cancer. Rare types include:
  • Follicular: Starts in the follicular cells of the thyroid. Follicular cells help to make hormones that regulate a person’s metabolism. This cancer usually does not spread to lymph nodes, but can spread to other body parts. It usually affects people over the age of 50.
  • Medullary: Starts in the C cells of the thyroid. C cells produce a hormone called calcitonin, which helps control calcium in the body. High levels of calcitonin in the blood can indicate this kind of cancer at an early stage. It can spread to lymph nodes and other body parts.
  • Anaplastic: A very rare, fast-spreading form of thyroid cancer, thought to sometimes develop from an already existing thyroid cancer. It typically occurs in people older than 60.

What are the symptoms of thyroid cancer?

Symptoms may not appear early on in the disease, but they include:
  • A lump in the neck
  • Hoarseness and/or other voice changes
  • Difficulty swallowing
  • Difficulty breathing
  • Neck and throat pain/swelling
  • Chronic cough
  • Swollen lymph nodes in the neck

What causes thyroid cancer?

Normal, healthy cells grow at a steady rate, and die at a set time. However, sometimes healthy cells develop abnormalities; they grow and multiply at an out of control rate, and take much longer to die. When this happens to cells in the thyroid, they accumulate into a tumor there. The exact cause of thyroid cancer is not clear. One risk factor involves exposure to high radiation levels, including radiation treatments to the head and/or neck, as well as professions that involve exposure. Head and neck exposure to radiation can especially increase the risk of thyroid cancer in children. Other risk factors are genetic; genetic diseases like multiple endocrine neoplasia type 2A and type 2B syndromes, or just having a history of thyroid cancer in the family, can increase the likelihood of developing it.

How is thyroid cancer diagnosed?

Thyroid cancer is diagnosed using the following procedures:
  • Physical examination
  • Blood tests
  • Biopsy
  • CT scan
  • PET scan
  • Ultrasound
  • Radioiodine scan
  • Genetic counseling
After diagnosis, various imaging tests (CT scans, MRIs, X-rays) are used to find out if the cancer cells have spread to other parts of the body. This is called staging.

What are the stages of thyroid cancer?

Doctors use the information obtained during diagnosis to assign a patient’s cancer a stage. Thyroid cancer stages are, approximately:
  • Stage I: The cancer is confined to the thyroid.
  • Stage II: The cancer has likely spread to nearby lymph nodes, and might have spread to other parts of the body.
  • Stage III: The cancer is any size and has spread extensively beyond the thyroid gland into nearby tissues and lymph nodes
  • Stage IV: The cancer is any size and has spread extensively to distant parts of the body.

What are the treatments for thyroid cancer?

Thyroid cancer treatment includes, but is not limited to:
  • Surgical removal of all or most of the thyroid
  • Surgical removal of lymph nodes in the neck
  • Ongoing thyroid hormone therapy (medication)
  • Radioactive iodine treatment
  • Radiation therapy
  • Chemotherapy
  • Alcohol ablation
  • Targeted drug therapy

Where can I find out more about thyroid cancer?

Thyroid Cancer Articles