What Is Tarlatamab?
Tarlatamab is an investigational medication being developed as an anti-cancer drug. It is administered as an intravenous (i.v.) infusion. Clinical trials are currently evaluating its efficacy and safety in various cancer types. The drug is being studied for its potential to treat aggressive neoplasms, particularly neuroendocrine carcinomas.
As of the latest data, 32 clinical trials are investigating tarlatamab, with a total enrollment of 4,666 participants. These trials began as early as 2017 and are projected to continue until at least 2026. Tarlatamab is being developed by sponsors including Amgen, the National Cancer Institute (NCI), and various academic and network foundations.
Uses and Conditions Under Study
Tarlatamab is primarily under investigation for the treatment of various cancers, with a significant focus on lung and central nervous system tumors. The drug is being studied to determine how well it works and to identify any potential side effects.
- Small Cell Lung Cancer (SCLC): Tarlatamab is extensively studied for small cell lung cancer, including extensive stage SCLC and carcinoma, small cell lung. A total of 13 trials are exploring tarlatamab's role in this aggressive form of lung cancer, including its use as a maintenance treatment after chemo-radiotherapy.
- Central Nervous System (CNS) Tumors: This includes conditions such as astrocytic tumor, adult brain metastases, adult CNS tumor, and childhood CNS tumor. Tarlatamab is being investigated for its potential to treat these challenging brain and spinal cord cancers, with 4 trials specifically listed for these conditions.
- Other Cancers: Tarlatamab is also being explored in other cancer types, including bladder cancer and cervical cancer. These studies aim to assess its effectiveness across a broader range of malignancies.
Dosing
Tarlatamab is administered as an intravenous (i.v.) infusion. The dosing regimens being studied vary across trials, often involving an initial step-dosing phase followed by regular maintenance doses.
A common investigational dosing schedule involves:
- An initial dose of 1 mg on day 1 of the first cycle.
- Followed by 10 mg on day 8 and day 15 of the first cycle.
- Subsequent doses of 10 mg are then administered every two weeks (Q2W) in cycles of 28 days.
Treatment typically continues until the disease progresses, unacceptable toxicity occurs, or the patient decides to discontinue. Some trials also investigate tarlatamab as a maintenance treatment following sequential chemo-radiotherapy, or in combination with other therapies like durvalumab, carboplatin, and etoposide. Dose exploration and expansion parts are common in these studies to determine optimal dosing, including "low dose" and "high dose" strategies, though specific numerical values beyond 1 mg and 10 mg are not detailed.
Side Effects
In a study (NCT04702737) involving 40 participants with neuroendocrine prostate cancer, all participants experienced at least one treatment-emergent adverse event (TEAE) and one treatment-related adverse event (TRAE). One participant (2.5%) experienced a dose-limiting toxicity (DLT).
In another study (NCT04885998) evaluating Tarlatamab in combination with AMG 404 for small cell lung cancer, dose-limiting toxicities were observed in 0 participants in Part 1 Cohort 1, 1 participant (20%) in Part 1 Cohort 2, and 1 participant (33.3%) in Part 1 Cohort 3. Specific individual side effects and their frequencies, as well as comparisons to a placebo group, were not detailed in the provided data.
Clinical Trial Results
Tarlatamab for Neuroendocrine Prostate Cancer
In a study (NCT04702737) of Tarlatamab in participants with neuroendocrine prostate cancer, the objective response rate (ORR) was 12.0% of participants, meaning this percentage of patients experienced a significant reduction in their cancer. The disease control rate (DCR), which includes patients with stable disease, was 36.0%. The median overall survival (OS) was 7.9 months, and the median radiographic progression-free survival (PFS) was 2.1 months. The drug's terminal elimination half-life was approximately 7.23 days.
Tarlatamab in Combination for Small Cell Lung Cancer
A study (NCT04885998) investigating Tarlatamab in combination with AMG 404 for small cell lung cancer (SCLC) showed varying results across different dose cohorts:
- In Part 1 Cohort 3 (Tarlatamab Dose D + AMG 404), the objective response rate (ORR) was 66.7% of participants, with a disease control rate (DCR) also at 66.7%. The median duration of response (DOR) was 8.1 months, and median progression-free survival (PFS) was 6.5 months.
- In Part 2 Dose Expansion Cohort (Tarlatamab Dose B + AMG 404), the ORR was 37.5%, and the DCR was 50.0%. The median duration of response (DOR) was 11.2 months, and median progression-free survival (PFS) was 7.4 months.
- Overall survival (OS) in Part 1 Cohort 3 was a median of 6.5 months.
Tarlatamab Monotherapy for Relapsed Small Cell Lung Cancer
A study (NCT05740566) comparing Tarlatamab to standard of care (SOC) chemotherapy in relapsed small cell lung cancer found that participants treated with Tarlatamab (1 mg to 10 mg every two weeks) had a median overall survival (OS) of 13.6 months, compared to 8.3 months for those receiving SOC chemotherapy.
Tarlatamab for Advanced Small Cell Lung Cancer in Chinese Participants
In a study (NCT06502977) of Tarlatamab in Chinese participants with advanced small cell lung cancer after two or more prior lines of treatment, the objective response rate (ORR) was 38.7% of participants.
Currently Recruiting Trials
Tarlatamab is currently being investigated in a range of clinical trials for various cancers, offering hope for patients with challenging diagnoses. These studies aim to understand how tarlatamab, often a bispecific antibody, can effectively target cancer cells and improve patient outcomes.
For patients with extensive-stage small cell lung cancer (SCLC), an aggressive form of lung cancer that has spread, several trials are actively recruiting. One Phase 2 study, NCT07423585, is evaluating tarlatamab as a treatment, aiming to enroll 39 participants. Another significant Phase 3 trial, NCT07005128, is comparing tarlatamab in combination with durvalumab, carboplatin, and etoposide against durvalumab, carboplatin, and etoposide alone, with a target enrollment of 330 patients. Additionally, a Phase 1 study, NCT06598306, is exploring the safety and tolerability of subcutaneous tarlatamab for extensive-stage SCLC in 220 participants.
Beyond extensive-stage SCLC, tarlatamab is also being studied for limited-stage SCLC. The Phase 3 trial NCT06117774 is comparing tarlatamab to placebo as a maintenance treatment after chemoradiotherapy, with plans to enroll 400 participants. Another Phase 2 study, NCT07242547, focuses on tarlatamab as maintenance treatment after chemo-radiotherapy for 37 limited-stage SCLC patients.
The research extends to neuroendocrine carcinomas (NECs), a diverse group of tumors. A Phase 3 trial, NCT06937905, is assessing tarlatamab against standard chemotherapy in 129 patients with pre-treated advanced pulmonary or gastroenteropancreatic poorly differentiated NECs. For advanced digestive NECs, the Phase 2 study NCT07061080 is investigating tarlatamab alone or in combination with FOLFIRI in 87 participants. Tarlatamab is also being explored for central nervous system (CNS) tumors, including gliomas, in a Phase 1/2 trial, NCT07243470, aiming for 70 participants, and for metastatic prostate cancer in the Phase 2 study NCT07111507, targeting 32 patients.
Where to Participate
Clinical trials for tarlatamab are currently accessible across a broad geographic area, with 86 sites located in 67 cities across 31 states. This wide reach aims to make participation convenient for more patients. Locations with multiple active studies include:
- Seattle, Washington (5 sites)
- Los Angeles, California (5 sites)
- Boston, Massachusetts (4 sites)
- Sioux Falls, South Dakota (3 sites)
- New Haven, Connecticut (3 sites)
Eligibility criteria for tarlatamab trials generally specify participants between 12 and 99 years of age, and all genders are welcome. These studies are specifically designed for patients with certain medical conditions, and healthy volunteers are not being recruited.
Development Timeline
The clinical development of tarlatamab began on October 24, 2017. Early investigations initially explored its potential for conditions such as IBS-C and hyperphosphatemia. However, the focus of tarlatamab's development soon shifted and significantly broadened, primarily driven by Amgen, which sponsors 16 of the 32 total trials. The research pipeline expanded to target a wide array of cancers, particularly small cell lung cancer (SCLC) and various neuroendocrine carcinomas. This strategic pivot towards oncology reflects tarlatamab's potential to treat aggressive and difficult-to-treat tumors.
As development progressed, trials moved through different stages, with 15 Phase 2 studies and 5 Phase 3 studies currently underway, indicating advanced stages of research. The total enrollment across all trials has reached 4,666 participants. The latest trial is projected to conclude in April 2026, highlighting the ongoing commitment to understanding tarlatamab's full potential across diverse cancer types, including gliomas, prostate cancer, and other DLL3-expressing tumors.