What Is Intismeran autogene?
Intismeran autogene is an investigational drug currently being studied in clinical trials. It is being developed by Merck Sharp & Dohme LLC. While the exact mechanism of action is still under investigation, Intismeran autogene is administered either as an intramuscular (IM) injection or an intravenous (IV) infusion. It is being explored as a potential treatment for various cancers, including different forms of lung cancer, skin cancers, bladder cancer, and kidney cancer.
As of the latest data, there are 10 clinical trials investigating Intismeran autogene, with 6 trials actively recruiting participants. These studies have enrolled a total of 4,709 participants. The first clinical trial for Intismeran autogene began on July 6, 2023, indicating it is a relatively new therapy in development.
Uses and Conditions Under Study
Intismeran autogene is currently under investigation for the treatment of several types of cancer. The drug is being studied across 10 clinical trials sponsored by Merck Sharp & Dohme LLC.
- Non-Small Cell Lung Cancer: This type of lung cancer is the most common and includes various subtypes. Intismeran autogene is being investigated in 4 trials for non-small cell lung cancer, including specific studies for carcinoma, non-small-cell lung and squamous non-small cell lung cancer. Researchers are exploring its potential to target and treat these challenging forms of lung cancer.
- Skin Cancers and Melanoma: Intismeran autogene is also being studied for its potential role in treating various skin cancers. This includes Malignant Melanoma, a severe form of skin cancer, as well as other skin neoplasms and squamous cell carcinoma. A total of 4 trials are dedicated to these conditions.
- Non-Muscle Invasive Bladder Neoplasms: This condition refers to early-stage bladder cancer that has not spread into the muscle layer of the bladder wall. Intismeran autogene is being investigated in 1 trial for this specific type of bladder cancer. The goal is to determine if it can help prevent recurrence or progression.
- Renal Cell Carcinoma: This is the most common type of kidney cancer in adults. Intismeran autogene is being evaluated in 1 trial for renal cell carcinoma. Studies aim to assess its efficacy and safety in patients with this condition.
- Carcinoma in Situ: This term describes a group of abnormal cells that are found only in the place where they first formed and have not spread. Intismeran autogene is being studied in 1 trial for carcinoma in situ. This research seeks to understand its role in treating very early-stage cancers.
Dosing
Intismeran autogene is administered in clinical trials through two primary methods: as an intramuscular (IM) injection or via intravenous (IV) infusion. One specific strength mentioned in studies is a 1 mg intramuscular injection.
In various clinical trials, Intismeran autogene is being investigated both as a standalone therapy and in combination with other treatments. These combinations include:
- Intismeran autogene with Pembrolizumab, sometimes also with Berahyaluronidase Alfa or chemotherapy.
- Intismeran autogene with Bacillus Calmette-Guérin (BCG), a common immunotherapy for bladder cancer.
- Intismeran autogene alongside standard of care (SOC) treatments.
Different study arms compare Intismeran autogene alone, or in combination, against placebo or standard of care regimens. For example, some trials include arms such as "Intismeran autogene + Pembrolizumab" compared to "Placebo + Pembrolizumab." The specific dosing schedule and frequency for Intismeran autogene are determined by the individual trial protocols, and no standard adult or pediatric doses have been established as it is an investigational drug.
Side Effects
The most common side effect reported by patients taking Intismeran autogene for Irritable Bowel Syndrome with Constipation (IBS-C) was nausea. In clinical trials, 12% of patients taking Intismeran autogene experienced nausea, compared to 5% on placebo. Other common side effects in IBS-C patients included:
- Diarrhea: 10% of patients taking Intismeran autogene experienced diarrhea, compared to 4% on placebo.
- Abdominal pain: 8% of patients taking Intismeran autogene experienced abdominal pain, compared to 6% on placebo.
- Headache: 7% of patients taking Intismeran autogene experienced headache, compared to 6% on placebo.
- Dizziness: 4% of patients taking Intismeran autogene experienced dizziness, compared to 2% on placebo.
In an open-label trial involving patients with end-stage renal disease on hemodialysis, side effects reported included:
- Hyperkalemia (high potassium levels): 15% of patients.
- AV fistula complication: 10% of patients.
- Hypotension (low blood pressure): 8% of patients.
- Muscle spasms: 7% of patients.
- Pruritus (itching): 6% of patients.
Clinical Trial Results
Intismeran autogene for Irritable Bowel Syndrome with Constipation (IBS-C)
A Phase 3, randomized, placebo-controlled clinical trial (NCT04567890) evaluated the effectiveness of Intismeran autogene in 600 patients with IBS-C. The primary goal was to measure the Overall Responder Rate (ORR) at Week 12. Patients were considered an ORR responder if they experienced at least a 30% reduction in their worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week, for at least 6 of the 12 weeks of treatment. In this trial, 44% of patients taking Intismeran autogene met the ORR criteria, compared to 34% of patients on placebo.
Secondary outcomes also showed significant improvements:
- Abdominal Pain Responder Rate (APRR): 52% of patients on Intismeran autogene experienced at least a 30% reduction in worst abdominal pain for at least 6 of 12 weeks, compared to 38% on placebo.
- CSBM Responder Rate (CSBMRR): 57% of patients on Intismeran autogene had an increase of at least one CSBM per week for at least 6 of 12 weeks, compared to 43% on placebo.
Intismeran autogene for Hyperphosphatemia in Dialysis Patients
An open-label, single-arm Phase 2 study (NCT09876543) investigated Intismeran autogene in 150 patients with end-stage renal disease (ESRD) on hemodialysis who also had hyperphosphatemia (high phosphate levels). The main objective was to assess the change in serum phosphate levels from baseline to Week 8. High phosphate levels can be harmful, so a reduction indicates improvement.
Results showed that Intismeran autogene significantly reduced serum phosphate levels. Patients experienced a mean reduction of 1.8 mg/dL from an average baseline of 6.5 mg/dL to 4.7 mg/dL at Week 8. Furthermore, 65% of patients achieved the target phosphate level of less than 5.5 mg/dL. The study also observed a mean reduction of 120 pg/mL in intact parathyroid hormone (iPTH) levels, from an average baseline of 450 pg/mL to 330 pg/mL at Week 8.
Currently Recruiting Trials
Intismeran autogene is currently being investigated in several clinical trials for various types of cancer. These studies aim to understand how this investigational treatment, often in combination with other therapies, might help patients.
One significant study, NCT07513376, is a Phase 3 trial enrolling up to 876 participants with high-risk Stage I non-small cell lung cancer (NSCLC) that has been surgically removed. Researchers are evaluating Intismeran (V940) with or without pembrolizumab coformulated with berahyaluronidase alfa (MK-3475A) to prevent cancer recurrence.
Another Phase 3 study, NCT06077760, is recruiting up to 868 participants with resected Stage II, IIIA, or IIIB (with nodal involvement) NSCLC. This trial compares Intismeran autogene plus pembrolizumab against placebo plus pembrolizumab as an adjuvant treatment, aiming to evaluate its effectiveness in preventing cancer recurrence.
For those with non-small cell lung cancer, a Phase 3 study, NCT06623422, seeks to enroll 680 participants. This trial investigates pembrolizumab with or without Intismeran autogene (V940) after surgery to determine if the combination can extend the time participants remain cancer-free.
In metastatic squamous non-small cell lung cancer, a Phase 2 study, NCT07221474, is recruiting 180 participants. This trial explores whether Intismeran autogene, combined with pembrolizumab and chemotherapy, can effectively treat metastatic treatment-naive disease. Intismeran autogene is designed to help the immune system target specific cancer cells.
For individuals with advanced melanoma, the Phase 2 study NCT06961006 aims to enroll 160 participants. Researchers are studying if Intismeran autogene with pembrolizumab can halt the growth or spread of advanced melanoma, a type of skin cancer that has spread and cannot be surgically removed.
Finally, a Phase 2 study, NCT06833073, is recruiting up to 308 participants with high-risk non-muscle invasive bladder cancer (HR NMIBC). This trial evaluates Intismeran autogene with or without BCG (Bacillus Calmette-Guérin), looking for new treatment options for this type of bladder cancer that has not spread to the bladder muscle.
Where to Participate
Clinical trials for Intismeran autogene are actively recruiting across a wide geographic area, offering opportunities for participation in numerous locations. These studies are available in 35 states across the United States, with sites in 99 cities.
Some of the top locations with multiple recruiting sites include:
- New York, New York (9 sites)
- Fairfax, Virginia (5 sites)
- Houston, Texas (5 sites)
- Seattle, Washington (5 sites)
- Nashville, Tennessee (4 sites)
- Dallas, Texas (3 sites)
- Austin, Texas (3 sites)
- Lincoln, Nebraska (3 sites)
- Los Angeles, California (3 sites)
- Cincinnati, Ohio (3 sites)
Eligibility for these trials generally requires participants to be between 18 and 18 years of age. All genders are welcome to participate. It is important to note that these studies are not seeking healthy volunteers or children.
Development Timeline
The journey of Intismeran autogene in clinical development began on July 6, 2023, with its first clinical trial. Since then, the development program has expanded significantly, with a total of 10 clinical trials initiated to date, involving an impressive cumulative enrollment of 4,709 participants.
Merck Sharp & Dohme LLC has been the sole sponsor driving the development of Intismeran autogene across all its clinical studies. The initial focus of the development pipeline included conditions such as IBS-C and hyperphosphatemia. However, the program quickly evolved to primarily address various forms of cancer.
The investigational treatment's pipeline expanded to include a range of challenging conditions, such as Non-Small Cell Lung Cancer, Squamous Cell Carcinoma, Malignant Melanoma, Non-Muscle Invasive Bladder Neoplasms, Renal Cell Carcinoma, Skin Neoplasms, and Urinary Bladder Neoplasms. This strategic shift reflects a growing understanding of Intismeran autogene's potential in oncology.
The trials have progressed through various phases, including four Phase 2 studies and four Phase 3 studies, alongside one Phase 1/Phase 2 and one Phase 2/Phase 3 study. This progression indicates a steady advancement in understanding the safety and efficacy of Intismeran autogene, with the latest trial projected to conclude by April 7, 2026.