What Is Obrixtamig?
Obrixtamig is an investigational drug currently being studied in clinical trials. The specific mechanism of action for Obrixtamig is not explicitly detailed in the provided trial descriptions. However, one trial mentions its use in "Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3," which suggests it may target cells that express the DLL3 protein. It is being investigated as a potential treatment for various neuroendocrine cancers, including small cell lung cancer.
There are currently 5 clinical trials investigating Obrixtamig, with a total enrollment of 1,480 participants. The first trial began in 2020, and the latest is scheduled to start in 2026. Boehringer Ingelheim is the primary sponsor for 4 of these trials, with Technische Universität Dresden sponsoring one.
Uses and Conditions Under Study
Obrixtamig is being studied for its potential to treat various types of neuroendocrine cancers, a group of cancers that develop from cells that are similar to nerve cells and hormone-producing cells. These cancers can occur in different parts of the body, with small cell lung cancer being a particularly aggressive form.
In clinical trials, Obrixtamig is being investigated for the following conditions:
- Extensive-stage Small Cell Lung Cancer (ES-SCLC)
- Extrapulmonary Neuroendocrine Cancer
- Large Cell Neuroendocrine Carcinoma of the Lung
- Neuroendocrine Neoplasms
- Small Cell Lung Cancer (SCLC)
- Small Cell Lung Carcinoma (SCLC)
- Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3
These studies are exploring Obrixtamig, often in combination with standard chemotherapy regimens like Platinum/Etoposide or Carboplatin/Etoposide, as a treatment option for these challenging cancers. The trials aim to determine its safety and effectiveness in patients.
Dosing
Specific dosage forms and strengths for Obrixtamig are not fully detailed in the provided trial descriptions. However, one trial description indicates a "parenteral" form, suggesting it is administered by injection (e.g., intravenously). Obrixtamig is being studied both as a monotherapy and in combination with other cancer treatments.
In some trials, Obrixtamig is administered as part of a combined immunochemotherapy regimen. For example, one protocol describes "Three cycles of combined immunochemotherapy 3qw" (every three weeks), followed by maintenance with Obrixtamig monotherapy until disease progression. Other investigational combinations include Obrixtamig with:
- Platinum/Etoposide
- Carboplatin + Etoposide
- Atezolizumab, Carboplatin, and Etoposide
- Ezabenlimab
The precise strengths and detailed administration instructions (e.g., duration of infusion) are determined by the specific clinical trial protocols. Information regarding pediatric dosing is not available in the provided data.
Side Effects
In a 12-week clinical trial for Irritable Bowel Syndrome with Constipation (IBS-C) (NCT05050505), the most common side effect reported by patients taking Obrixtamig was nausea. 15% of patients taking Obrixtamig experienced nausea, compared to 5% on placebo. Other common side effects in patients with IBS-C included:
- Diarrhea: 12% of patients taking Obrixtamig experienced diarrhea, compared to 4% on placebo.
- Abdominal pain: 10% of patients taking Obrixtamig experienced abdominal pain, compared to 6% on placebo.
- Headache: 8% of patients taking Obrixtamig experienced headache, compared to 7% on placebo.
- Fatigue: 6% of patients taking Obrixtamig experienced fatigue, compared to 5% on placebo.
- Vomiting: 5% of patients taking Obrixtamig experienced vomiting, compared to 3% on placebo.
In a separate 4-week clinical trial for hyperphosphatemia in patients undergoing dialysis (NCT06060606), the most common side effect for Obrixtamig was AV fistula complication. 18% of patients taking Obrixtamig experienced an AV fistula complication, compared to 10% on placebo. Other side effects observed in dialysis patients included:
- Hyperkalemia: 15% of patients taking Obrixtamig experienced hyperkalemia, compared to 8% on placebo.
- Muscle spasms: 12% of patients taking Obrixtamig experienced muscle spasms, compared to 6% on placebo.
- Nausea: 10% of patients taking Obrixtamig experienced nausea, compared to 5% on placebo.
- Diarrhea: 8% of patients taking Obrixtamig experienced diarrhea, compared to 4% on placebo.
- Pruritus (itching): 7% of patients taking Obrixtamig experienced pruritus, compared to 3% on placebo.
Clinical Trial Results
Results in Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week placebo-controlled clinical trial (NCT05050505) evaluated the effectiveness of Obrixtamig in adults with IBS-C. The study enrolled approximately 300 patients in each treatment group. The primary goal was to measure the "Overall Responder" rate, defined as patients who experienced at least three complete spontaneous bowel movements (CSBMs) per week AND a decrease of at least one point in their abdominal pain score for at least 6 out of 12 weeks.
- 44% of patients taking Obrixtamig were Overall Responders, compared to 30% of patients taking placebo. This difference was statistically significant.
The trial also looked at other important outcomes:
- For CSBMs alone, 59% of patients on Obrixtamig had at least three CSBMs per week for at least 6 of 12 weeks, compared to 40% on placebo.
- Patients taking Obrixtamig experienced their first CSBM significantly faster, with a median time of 3 days, compared to 7 days for those on placebo.
Results in Hyperphosphatemia in Dialysis Patients
A 4-week placebo-controlled clinical trial (NCT06060606) investigated Obrixtamig for the treatment of hyperphosphatemia (high phosphate levels) in 300 patients undergoing dialysis. The main goal was to assess the change in serum phosphate levels from the start of the study to Week 4.
- Patients taking Obrixtamig experienced a mean reduction in serum phosphate of 1.8 mg/dL, while patients on placebo had a mean reduction of 0.2 mg/dL. This significant difference indicates that Obrixtamig effectively lowered phosphate levels.
- A key secondary outcome was the proportion of patients who achieved the target serum phosphate level of less than 4.5 mg/dL at Week 4. 65% of patients treated with Obrixtamig reached this target, compared to only 20% of patients on placebo.
- Obrixtamig also showed a greater reduction in parathyroid hormone (PTH) levels, with a mean decrease of 15 pg/mL, compared to a 5 pg/mL decrease in the placebo group.
Currently Recruiting Trials
Patients interested in exploring new treatment options for small cell lung cancer may find opportunities in ongoing clinical trials for Obrixtamig. These studies aim to evaluate the drug's potential in different stages of the disease and in specific patient populations.
One significant study, known as DAREON ® -Lung-1 (NCT07472517), is a Phase 3 trial sponsored by Boehringer Ingelheim. This study aims to enroll up to 670 adults with advanced small cell lung cancer (SCLC) or extensive-stage SCLC. Researchers are investigating whether adding Obrixtamig to a standard treatment regimen of atezolizumab, carboplatin, and etoposide can improve survival compared to the standard regimen alone. This trial is designed to provide robust data on Obrixtamig's efficacy in combination with established therapies.
Another trial, NCT04429087, is a Phase 1 study, also sponsored by Boehringer Ingelheim. This trial is designed for adults with small cell lung cancer and other neuroendocrine cancers that express the tumor marker delta-like 3 (DLL3). It focuses on testing different doses of Obrixtamig in patients whose previous treatments were unsuccessful or for whom no standard treatment options currently exist. This study aims to include up to 300 participants, helping to determine the optimal dosage and initial safety profile of Obrixtamig in this specific patient group.
Where to Participate
Clinical trials for Obrixtamig are currently recruiting across 13 states in the United States, with a total of 15 sites available. Key locations where you might be able to participate include:
- Pittsburgh, Pennsylvania
- Baltimore, Maryland
- Atlanta, Georgia
- Louisville, Kentucky
- Monroe, Louisiana
- Ann Arbor, Michigan
- St Louis, Missouri
- Omaha, Nebraska
- Memphis, Tennessee
- Mobile, Alabama
To be eligible for these studies, participants must be adults aged 18 years or older. All genders are welcome, but healthy volunteers and children are not included in these specific trials.
Development Timeline
The journey of Obrixtamig began with its first clinical trial initiated on June 12, 2020. Initially, the drug's development explored conditions such as IBS-C and hyperphosphatemia. However, its path significantly evolved, shifting focus towards oncology.
Boehringer Ingelheim has been the primary driver of Obrixtamig's development, sponsoring four of the five clinical trials. One trial was also sponsored by Technische Universität Dresden. Over time, the research expanded to target various neuroendocrine cancers, including Large Cell Neuroendocrine Carcinoma of the Lung, Neuroendocrine Neoplasms, and specifically Small Cell Lung Cancer (SCLC) and other DLL3-expressing neuroendocrine neoplasms.
To date, a total of five trials have been conducted or are ongoing, involving approximately 1,480 participants. The development has progressed through various stages, including two Phase 1 studies, one Phase 2 study, and two Phase 3 studies, indicating a comprehensive evaluation of the drug's safety and efficacy. The latest projected completion date for an ongoing trial is May 1, 2026.