A Phase 1/2 interventional study of Tarlatamab and Concurrent Radiation Therapy in Melanoma, Medullary Thyroid Cancer and Sinonasal Undifferentiated Carcinoma, sponsored by University of Arizona. Recruiting at 3 sites in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-10-06.
Sponsored by University of Arizona · Phase 1/2, Interventional, and Treatment
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.
This is a Phase I, Open label, Single Arm, Multi-center Study, with nested Phase II to examine safety of standard palliative and consolidative RT regimens in a main cohort of patients with tumor histologies with high prevalence of DLL3 (N=20-24) with an extracranial site (primary or metastatic) amenable to radiation (not allowing for re-irradiation of the same lesion, with a minimum of 10 thoracic sites. Given the potential toxicity of ICANS with tarlatamab, once deemed safe in the main cohort, we will allow for expansion for treatment of cranial sites amenable to radiation (excluding lesion re-irradiation except for stereotactic radiosurgery / fractionated stereotactic radiosurgery [SRS/fSRS] after prior whole brain RT or prophylactic cranial irradiation [PCI]) with continued enrollment in the main cohort.
Given the need to determine safety of administration of tarlatamb with RT, if safety is not met for concurrent administration in the main cohort, we would discontinue concurrent treatment, and assess safety in a sequential RT and tarlatamab cohort, as temporal de-escalation. If safety is not met in the sequential cohort, treatment with RT will be discontinued and enrollment will continue with tarlatamab monotherapy, not requiring patients having a site amenable to RT and enriching for patients without SCLC.
In the nested phase II, we will assess efficacy of radiation and tarlatamab amongst patients with tumors with high prevalence of DLL3 or those who have positive DLL3 (≥1% per IHC), including but not exclusive to SCLC. This would allow for potential evaluation of safety and response for tumors beyond the DeLLPhi 300/301 studies.
The study population will include patients ≥18 years of age with primary/metastatic sites amenable to external beam radiation treatment refractory solid tumors of:
Up to 30 patients will be enrolled.
3,370 studies on the registry are indexed under Melanoma; 578 are open to participants now.
This study's planned enrollment of 30 is below the median of 40 across 2,649 interventional studies indexed under Melanoma.
Browse Melanoma studies →University of Arizona is the lead sponsor of 476 studies on the registry; 88 are open to participants now.
Of its 51 completed or terminated interventional studies of FDA-regulated products, 30 (59%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
or cytologically confirmed :
Eligible for external beam radiation therapy to a previously unirradiated, measurable lesion as per standard of care.
a. For the concurrent / sequential cohort of extracranial RT sites: i. A minimum of 10 subjects with thoracic lesions (lung, mediastinum, thoracic spine, rib, or other thoracic sites) will be treated ii. Subjects with treated are eligible (untreated brain metastases are ineligible) provided they meet the following criteria:
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Any CNS disease is asymptomatic for at least 7 days (unless symptoms are deemed irreversible by the investigator), the patient is off for at least 7 days (physiologic doses of steroids are permitted), and the subject is off or on stable doses of anti-epileptic drugs for malignant CNS disease for at least 7 days.
b. For the concurrent/sequential cohort of cranial RT sites: i. Previously untreated brain lesions / are eligible ii. Subjects with previously irradiated brain lesions are eligible provided they meet one of the following criteria:
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1. Patients with previously irradiated lesions that have recurred or progressed are eligible 11. Adequate organ function, defined as follows:
a. Hematological function: i. ≥ 1.5 x 109/L ii. count ≥ 100 x 109/L iii. > 9 g/dL (90 g/L) b. Coagulation function: i. (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) ≤ 1.5 x institutional (ULN). Subjects on chronic anticoagulation therapy who do not meet the criteria above may be eligible to enroll after discussion with the medical monitor.
c. Renal function: i. Estimated (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculation > 30 mL/min/1.73 m2 d. hepatic function: i. (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) \< 3 x ULN (or \< 5 x ULN for subjects with liver involvement) ii. Total \< 1.5 x ULN (or \< 2 x ULN for subjects with liver metastases) e. Pulmonary function: i. No pleural effusion ii. Baseline oxygen saturation > 90% on room air f. cardiac function (if obtained as part of standard of care): i. Cardiac ≥ 50%, no clinically significant pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no clinically significant (ECG) findings
Exclusion Criteria:
Re-irradiation, unless it is SRS/hfSRT after whole-brain radiation therapy (WBRT) or PCI or WBRT after SRS/hfSRT; re-irradiation of same lesion, unless verified with the Principal Investigator; patients with lesions not amenable to RT (including previously irradiated) will be only allowable on the tarlatamab monotherapy cohort.
Disease Related
Subjects are excluded from the study if any of the following criteria apply:
a. No lesion(s)/site(s) amenable to radiation therapy (only eligible for tarlatamab monotherapy if open) b. Planned re-irradiation of a previously irradiated site c. requiring craniospinal irradiation
Other Medical Conditions
Subject with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of tarlatamab.
NOTE: Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. Subjects requiring oral antibiotics who have been afebrile > 24 hours, have no leukocytosis and have no clinical signs of infection are eligible. Subjects who meet these criteria and who were previously on IV antimicrobials should have been off IV antimicrobials for > 48 hours.
Exclusion of hepatitis infection based on the following results and/or criteria:
a. Positive for surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B).
b. Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.
c. Positive virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
NOTE: Testing required as per standard of care in suspected or known patients.
NOTE: Testing required as per standard of care in suspected or known patients.
Prior/Concomitant Therapy
Prior anti-cancer therapy within 30 days prior to first dose of tarlatamab.
Exceptions:
a. Subjects who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to grade ≤ 1.
The following vaccines (live and ) are excluded during the following study periods:
Other Exclusions
1. Female subjects of unwilling to use protocol specified method of during treatment and for an additional 60 days after the last dose of tarlatamab. Contraception methods for female subjects include:
Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments; the reliability of sexual abstinence must be evaluated in relation to the duration of the trial and the preferred and usual lifestyle of the subject) 2. Female subjects who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of tarlatamab.
3. Female subjects planning to become pregnant while on study through 60 days after the last dose of tarlatamab.
4. Female subjects of childbearing potential with a positive pregnancy test assessed at screening and/or day 1 by a highly sensitive urine or serum pregnancy test.
5. Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception (use a condom) during treatment and for an additional 60 days after the last dose of tarlatamab.
6. 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 tarlatamab.
7. Male subjects unwilling to abstain from donating sperm during treatment and for an 60 days after the last dose of tarlatamab.
8. Subject has known sensitivity to any of the products or components to be administered during dosing.
9. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (i.e., Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.
10. History or evidence of any other disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients enrolled to this cohort will receive tarlatamab with concurrent radiation therapy (RT) to extracranial sites (n=20-24 extracranial RT with a minimum of 10 thoracic patients). Patients will receive tarlatamab at a step-up dose of 1 mg on Cycle 1 Day 1 and then 10 mg on cycle 1 Day 8 and Cycle 1 Day 15 and every 2 weeks thereafter (on days 1 and 15 of each cycle) until radiographic progression or disease progression or 24 months, whichever is earlier. Patients will receive concurrent RT to extracranial sites as per standard of care starting as early as Cycle 1 Day 16 and as late as Cycle 2 Day 28, assuming there is no ongoing cytokine release syndrome (CRS) or immune-effector cell-associated neurotoxicity Syndrome (ICANS).
Drug: Tarlatamab · Radiation: Concurrent Radiation Therapy
If the safety endpoint in the Concurrent Main Cohort is met, enrollment will expand to the Concurrent Cranial Cohort. 6-10 patients will receive tarlatamab with concurrent radiation therapy to cranial sites as described in the Concurrent Main Cohort.
Drug: Tarlatamab · Radiation: Concurrent Radiation Therapy
If the concurrent main cohort safety endpoint is not met, then the study will proceed to de-escalation, where 20 patients will be enrolled on the sequential radiation therapy cohort. In this cohort patients will receive sequential tarlatamab and RT to cranial and extracranial RT sites. Standard of care RT can occur prior to Cycle 1 Day 1(if radiation treatment is completed \<7 days prior to the start of tarlatamab) or be interdigitated with tarlatamab with a 7-day washout between RT and infusion, with RT to begin as early as Cycle 1 Day 22 and as late as cycle 2 Day 28, assuming no ongoing CRS/ICANS.
Drug: Tarlatamab · Radiation: Sequential Radiation therapy
If the sequential safety endpoint is not met, then the study will proceed to another de-escalation phase, where 10 patients will receive tarlatamab alone.
Drug: Tarlatamab
Tarlatamab will be administered at a step-up dose of 1mg on Cycle 1 Day 1 and then 10 mg on Cycle 1 Day 8 and Cycle 1 Day 15 and every 2 weeks thereafter. For cycle 2 onwards, tarlatamab infusion will occur every 2 weeks on days 1 and 15 of each cycle.
Standard of care RT can begin as early as Cycle 1 Day 16 and as late as Cycle 2 Day 28, assuming there is no ongoing CRS (extracranial)/ICANS (cranial).
Standard of care radiation therapy can occur prior to Cycle 1 Day 1 (if radiation treatment is completed \<7 days prior to the start of tarlatamab) or be interdigitated with tarlatamab with a 7-day washout between RT and infusion, with RT to begin as early as Cycle 1 Day 22 and as late as cycle 2 Day 28, assuming no ongoing CRS (extracranial)/ICANS (cranial).
Percentage of participants experiencing dose limiting toxicities (DLT) attributed to radiation or combination of radiation and tarlatamab.
The primary endpoint is safety, which will be measured by DLT using adverse events graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and ASTCT (CRS and ICANS). DLT will be defined as having 1) grade 3 - 5 non-hematologic adverse events (AEs) possibly, probably or definitely related to protocol treatment (radiation or combination of radiation and tarlatamab) by 8 weeks from start of radiation therapy; or 2) AEs possibly, probably, or definitely related to radiation or combination of radiation and tarlatamab leading to early termination of radiation or permanent discontinuation of tarlatamab. Grade 3+ AEs (or discontinuation) due to tarlatamab alone (not attributable to combination therapy) will not contribute to the primary endpoint. Frequency (%) of the patients with DLT will be reported by cohort.
Time frame: Until radiographic or disease progression or up to 24 months, whichever is earlier.
Objective response rate (ORR) using RESIST/iRECIST and RANO/RANO-BM criteria of radiated and non-radiated sites stratified by anatomic RT site and tumor histology.
ORR is defined as the percentage of subjects with measurable disease who have at least 1 confirmed response of complete response (CR) or partial response (PR) prior to any evidence of progression. ORR will be reported by cohort and site.
Time frame: Until radiographic or disease progression or up to 24 months, whichever is earlier.
Toxicity of tarlatamab in tumors in all patients, not of SCLC histology, and stratified by histology in accordance with CTCAE v5.
Assess toxicity of therapy (tarlatamab with radiation therapy) by the incidence of treatment emergent adverse events reported (to include SAEs and AEs leading to discontinuation) based on CTCAE v5 and ASTCT (CRS and ICANS), stratified by histology and by SCLC vs. tumors that are not SCLC. Counts of all AEs by grade will be provided by cohort.
Time frame: Until radiographic or disease progression or up to 24 months, whichever is earlier.
Overall survival (OS)
OS is defined as the time from registration to death and will be estimated using the Kaplan Meier method by cohort.
Time frame: Until radiographic or disease progression or up to 24 months, whichever is earlier.
Progression free survival (PFS)
PFS according to RECIST guidelines is defined as the time from registration to progressive disease or death, whichever occurs first, and will be estimated using the Kaplan Meier method by cohort and site if applicable.
Time frame: Until radiographic or disease progression or up to 24 months, whichever is earlier.
Duration or Response (DOR)
DOR will only be evaluated in participants with objective response of CR or PR. All confirmed responders will be followed for at least 6 months from the onset of initial response. The end of response will match with the date of progression or death from any cause used for the PFS endpoint. The DOR estimate will be summarized using Kaplan-Meier method by cohort.
Time frame: Until radiographic or disease progression or up to 24 months, whichever is earlier.
Plan to share: No
No publications or documents are linked to this record.
Started Sep 2025 (actual). Primary completion is estimated for May 2030, 56 months after the start.
Of 85 non-industry phase 1/2 interventional studies under Melanoma, half reached primary completion within 59 months of starting (the median), counting those still running; a quarter within 47 and three quarters within 98. This study's planned 56 months is close to that.
Counting every sponsor, half of 220 studies reached it within 61 months; a quarter within 42 and three quarters within 85.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: AMG 757