Carcinoma, Small Cell Lung, Limited-stage Small-cell Lung Cancer, Respiratory Tract Neoplasms, Thoracic Neoplasms
Conditions
Keywords
Non small cell lung cancer, Tarlatamab, Maintenance treatment, Antineoplastic Agents, Chemo-radiotherapy, Immunotherapy
Brief summary
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.
Detailed description
The study MERLIN is a phase II clinical trial intending to enroll 37 patients, who will receive will receive Tarlatamab as maintenance treatment. This is an open-label, phase II, exploratory and multi-centre clinical trial. Limited stage SCLC patients not eligible for concurrent chemo-radiotherapy will be selected. 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. For all patients, tumor response data collection will continue until disease progression, even if the patient stops study treatment prior to disease progression. Patients who still benefit from the drug treatment at the end of the study or at early termination of the clinical trial, will continue receiving the drug until progression disease. The primary objective is to evaluate the Progression free survival (PFS) in the intent-to-treat population. Progression free survival (PFS) defined as the time from enrollment to the date of the first documentation of disease progression according to RECIST 1.1 or death from any cause, whichever is earlier 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.
Interventions
DRUGTarlatamab
Patients will be enrolled in the trial after receiving sequential chemo-radiotherapy, if there is no progression disease, patients will receive tarlatamab maintenance treatment. Patients will receive maintenance with tarlatamab IV until disease progression unacceptable toxicity, patient or physician decision to discontinue or death. Patients who still benefit from the drug treatment at the end of the study or at early termination of the clinical trial, will continue receiving the drug until progression disease.
Sponsors
Fundación GECP
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented new diagnosis of LS-SCLC by histology or cytology from brushing, washing, or needle aspiration. Mixed tumors are not eligible. * Patients who: 1. were treated with sequential chemo-radiotherapy 2. were treated only with chemotherapy * Have at least one lesion that meets criteria for being measurable or non-measurable, as defined by RECIST 1.1. * Has completed chemo-radiation or chemotherapy alone without progression of disease per RECIST v1.1 * Be male or female ≥18 years of age inclusive, on the day of signing informed consent. * Have a life expectancy of at least 3 months from the study start. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to the first dose of study intervention. * Toxicities attributed to chemo-radiotherapy treatment have to be resolved to grade ≤1, unless otherwise specified. * No clinically significant electrocardiogram (ECG) findings * Correct pulmonary function without oxygen supplementation * Have voluntarily agreed to participate by giving written consent for the study prior to any specific protocol procedures. * Have adequate organ function (hematological and biochemistry parameters).
Exclusion criteria
* Patients expected to require any other form of radiation therapy for LS-SCLC as concurrent radiotherapy. * Extensive-stage SCLC (ES-SCLC) or any previous diagnosis of transformed non-small cell lung cancer. Mixed tumors (SCLC-NSCLC) are not eligible. * Has known history of, or active, neurologic paraneoplastic syndrome of autoimmune nature. * Has had major surgery within 4 weeks prior to first dose of study interventions. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. * Has known history of a second malignancy other than SCLC, unless potentially curative treatment has been completed with no evidence of malignancy for at least 3 years since the initiation of that therapy. * Uncontrolled intercurrent active infection at the time of enrollment requiring systemic therapy. * Evidence of interstitial lung disease or active, non-infectious pneumonitis. * History of solid organ transplantation. * Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association \>class II) within 6 months prior to first dose of study treatment. * Has a known history of Human Immunodeficiency Virus (HIV) infection. * Has a known history of Hepatitis B or known active Hepatitis C virus infection. * Has a known history of active tuberculosis. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Has serious nonhealing wound, ulcer, or bone fracture within 28 days before first dose of study intervention. * Female subjects of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 60 days after the last dose of study treatment. * Female subjects who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of study treatment. * Female subjects planning to become pregnant or donate eggs while on study through 60 days after the last dose of study treatment. * Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test. * Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence or use contraception during treatment and for an additional 60 days after the last dose of study treatment. * Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 60 days after the last dose of study treatment. * Subject has known sensitivity to any of the products or components to be administered during dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | From date of enrollment until the date of last follow up, assessed up to 24 months. | Efficacy of Tarlatamab as maintenance treatment assessed by progression free survival Progression-free survival, defined as the time from enrollment to the date of the first documentation of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death from any cause, whichever is earlier. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | From the date of enrollment to the date of last follow up, assessed up to 24 months | ORR: Describe the efficacy of Tarlatamab as maintenance treatment as assessed by objective response rate (ORR) Investigator-assessed ORR, defined as a confirmed complete response (CR) plus partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). According to RECIST 1.1, a complete response is the disappearance of all target lesions, and a partial response is defined as at least a 30% decrease in the sum of the target lesions. |
| Overall Survival (OS) | From the date of enrollment to 6 months, 1 and 2 years | OS at 6 months and 1 and 2 years, defined as the time from enrollment to the date of death from any cause |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | From the subject's written consent to participate in the study through 90 days after the final administration of the drug. | Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria. |
Countries
Spain
Contacts
CONTACTEva Pereira
STUDY_CHAIRMariano Provencio, MD
President of Grupo Español de Cáncer de Pulmón
Outcome results
None listed