Tarlatamab

The primary objective of this trial is to evaluate the safety and tolerability of tarlatamab in combination with ZL-1310 with or without durvalumab and to determine the maximum tolerated combination dose (MTCD) and/or recommended phase 2 dose (RP2D) of ZL-1310 in combination with tarlatamab.

The main objective of the study is to compare the efficacy of tarlatamab in combination with durvalumab, carboplatin and etoposide to the combination of durvalumab, carboplatin and etoposide on prolonging overall survival (OS).

The primary objective for dose exploration and dose expansion is to evaluate the safety and tolerability of tarlatamab in combination with AB248. The primary objective for dose exploration only is to determine the recommended dose for expansion and/or maximum tolerated combination dose (MTCD) of AB248 in combination with tarlatamab.

Extrapulmonary small cell carcinoma (EPSCC) or neuroendocrine carcinoma (NEC) is a rare but fatal disease. The prognosis of patients with advanced EPSCC or NEC failed platinum-etoposide chemotherapy is poor with median overall survival ranged 6 to 9 months. High expression levels of DLL3 has been demonstrated in many EPSCC or NEC. As tarlatamab, a bispecific T-cell engager with dual affinity for DLL3 on tumor cells and CD3 on T cells, has demonstrated clinically meaningful activity for patients with advanced small cell lung cancer. We thus hypothesize that tarlatamab also has clinically activity for patients with advanced EPSCC and NECs.

UNLOCK TARLATAMAB is an open-label, single arm, multicenter, phase 2 platform study that aims to evaluate the mechanisms of action and resistance to tarlatamab in metastatic/locally advanced Small-Cell Lung Cancer (SCLC) with any level of DLL3 expression and in other poorly differentiated Neuroendocrine Carcinomas (NECs) DLL3 positive. The two cohorts of patients are the following: i. cohort 1: patients with SCLC with any level of DLL3 expression. ii. cohort 2: patients with other poorly differentiated NECs whatever the primary or high grade medullary thyroid carcinoma DLL3 positive by immunohistochemistry (IHC). Patients enrolled in both cohorts will receive treatment with tarlatamab at the dose of 1 mg on D1, 10 mg on D8 and D15 and Q2W thereafter in a 28-day cycle. Tarlatamab will be administrated in intravenous route until disease progression, unacceptable toxicity, or consent withdrawal. Tumor and blood samples will be collected at baseline, on-treatment and at progression in order to identify biomarkers of drug response

The SPACE-T study is a clinical trial for people with advanced small-cell lung cancer (SCLC) whose cancer has returned or spread despite previous treatment and whose general health is reduced (ECOG performance status 2). The study will include 57 participants at about 15 sites in Germany. The study is testing tarlatamab, a treatment that helps the immune system recognize and attack cancer cells. Participants will receive tarlatamab through a vein, starting with a lower dose of 1 mg, followed by doses of 10 mg. Treatment will then generally be given every two weeks. The main purpose of the study is to find out how effective tarlatamab is in this group of patients by assessing how many participants are alive 12 months after starting the study. The study will also examine how well the treatment controls the cancer, including cancer that has spread to the brain, how well participants tolerate the treatment, its side effects, and its impact on quality of life. Patients with poorer general health are often not included in clinical trials, even though they represent an important part of the people treated for SCLC in everyday clinical practice. The SPACE-T study aims to provide more information about whether tarlatamab is effective and feasible for these patients.

The researchers are doing this study to find out whether tarlatamab is an effective treatment for Delta-like Protein 3 (DLL3)-positive prostate cancer that has spread to other parts of your body (metastasized) and has either come back after treatment (relapsed) or not responded to treatment (refractory).

The primary objective of this study is to demonstrate non-inferiority in pharmacokinetic (PK) parameters of subcutaneous (SC) vs intravenous (IV) tarlatamab administration and to characterize the efficacy, safety, and tolerability of SC tarlatamab in participants with relapsed extensive-stage small-cell lung cancer (ES-SCLC) after platinum-based chemotherapy.

A single arm phase II study evaluating intracranial efficacy of tarlatamab in patients with asymptomatic active brain metastases from small cell lung cancer (SCLC).

Phase I study to examine safety of the addition of concurrent tarlatamab with standard palliative and consolidative RT regimens , with a main cohort of N=20-24 patients with extracranial anatomic radiation sites. I) After lead in of 10 patients demonstrating safety of treatment, allow for expansion to cranial sites of disease (N=6-10) with continued enrollment in main cohort II) If toxicity criteria is not met in concurrent RT tarlatamab cohort, we will continue with sequential RT, either A) delivered within 7 days prior to cycle 1 day 1, or B) delivered during cycle 1 -2 but with pre- and post-RT washout of 7 days with no drug during RT, to examine safety in a temporally spaced setting. III) If sequential tarlatamab and radiation is not deemed safe, we would allow for continued enrollment to assess efficacy of drug sans radiation treatment, enriching for tumors not of small cell lung cancer histology and allowing for patients without sites amenable to RT. A nested phase II study will attempt to assess for ORR and safety of study intervention amongst tumors not of small cell lung cancer histology.

START-lung is an international, multicentre, single-arm phase II trial. Protocol treatment consists of tarlatamab administered as an intravenous infusion until disease progression according to RECIST v1.1 criteria, unacceptable toxicity, or patient decision, whichever comes first. The primary objective of the trial is to assess the clinical efficacy of tarlatamab, in terms of 12-month OS rate, in patients with ES-SCLC and ECOG PS 2 who have previously received only one line of platinum-etoposide doublet chemotherapy with immune-checkpoint inhibition and whose disease has progressed.

This is an open-label, phase II, exploratory and multi-centre clinical trial. 37 Limited stage SCLC patients not eligible for concurrent chemo-radiotherapy will be enroll. Patients will be enrolled in the trial after receiving sequential chemo-radiotherapy, if there is no progression disease, patients will be treated with maintenance Tarlatamab. Patients will receive maintenance with Tarlatamab IV until disease progression unacceptable toxicity, patient or physician decision to discontinue or death. The primary objective is to evaluate the Progression free survival (PFS). Patient accrual is expected to be completed within 2 years. Treatment and follow-up are expected to extend the study duration to a total of 5 years. Patients will be followed for 2 years after enrollment. The study will end once survival follow-up has concluded.

This phase II trial tests the effect of tarlatamab in treating patients with small-cell lung cancer (SCLC) that has spread from where it first started to other parts of the body (extensive-stage). SCLC is an aggressive cancer that has a low 5-year survival rate. Tarlatamab is a bispecific antibody that can bind to two different antigens at the same time. Tarlatamab binds to DLL3, a protein found on the surface of some types of tumor cells, including small-cell lung cancer, and to CD3, which is present on immune system T-cells (a type of white blood cell), and may interfere with tumor cell ability to grow and spread. This may increase the time to progression (growing, spreading, or worsening) and help patients with extensive-stage SCLC live longer.