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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Maastricht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AMGEN

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To evaluate the intracranial ORR of tarlatamab according to RANO-BM

Secondary objectives 6

1. - To evaluate the BM DCR and median CNS PFS of tarlatamab according to RANO-BM
2. - To evaluate the extracranial ORR and DCR of tarlatamab according to RECIST 1.1
3. - To evaluate the extracranial PFS of tarlatamab according to RECIST 1.1
4. - To evaluate the overall PFS of tarlatamab (RANO-BM for BM, RECIST 1.1 for extracranial lesions)
5. - To evaluate the OS of tarlatamab
6. - To evaluate the safety of tarlatamab according to CTCAE v5.0 criteria

Conditions and MedDRA coding

patients with asymptomatic active brain metastases from small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. - Patients with pathology proven metastatic SCLC
2. - Pretreated with at least platinum-doublet chemotherapy with or without immunotherapy, no max-imum of previous lines of systemic therapy
3. - At least one asymptomatic active (newly diagnosed or unequivocally progressive) untreated brain metastasis ≥ 5mm: o Subjects with largest measurable intracranial lesion ≥5 mm but <10mm may be allowed to enroll upon agreement with investigator (for patients with target lesions of ≥ 5mm but <10 mm, 1.5 mm slice thickness brain MRI is required). o "Untreated" refers to the lesion not being previously treated with stereotactic radiosur-gery/therapy (SRS/SRT) or surgery. o Prior treatment with whole brain radiation therapy or local surgery is permissible provided unequivocal progression in the lesion has since occurred
4. - WHO/ECOG PS 0-1 and estimated life expectancy 12 weeks or more
5. - For at least 7 days prior to study start: Patient must be asymptomatic from CNS metastases and on a stable dose of anti-epileptics and corticosteroids. Maximum dose of steroids is 10 mg predniso-lone or equivalent/day, dose should be noted.
6. - Adequate organ and bone marrow function, defined as: o Hematological function:  Absolute neutrophil count ≥1.5 x109/L  Platelet count ≥ 100 x109/L  Hemoglobin ≥ 5.6 mmol/l o Coagulation function:  Protrombin time (PT)/ international normalized ratio (INR) and partial thrombo-plastin time (PTT) or activated partial thromboplastin time (APTT) ≤ 1.5 x institu-tional upper limit of normal (ULN) except for subjects receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to start of study treatment. o Renal function:  Estimated glomerular filtration rate (eGFR) based on Modification of Dietin Renal Disease (MDRD) calculation < 30 mL/min/1.73 m2 o Hepatic function:  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3x ULN (or < 5x ULN for subjects with liver metastases)  Total bilirubin < 1.5x ULN (or < 2x ULN for subjects with liver metastases), except for subjects with Gilberts disease o Pulmonary function:  No oxygen supplementation o Cardiac function:  Cardiac ejection fraction ≥50%, no clinically significant pericardial effusion as de-termined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no clinically significant electrocardiogram (ECG) finding
7. - Age 18 years or older
8. - Signed and written informed consent

Exclusion criteria 30

1. - Symptomatic BM (if asymptomatic with corticosteroids with a maximum dose of steroids of 10 mg prednisolone or equivalent/day, the patient is eligible). If in doubt, discussion with the sponsor is necessary
2. - Leptomeningeal metastases (evaluated with MRI brain)
3. - BM in eloquent area (to be discussed with neuro-oncologist)
4. - Contra-indication for MRI
5. - Prior history of severe or life-threatening events from any immune-mediated therapy
6. - Grade 2 or higher toxicity from previous systemic therapy, except for alopecia
7. - History of other malignancy within the past 2 years, with the following exceptions: o Malignancy treated with curative intent before enrolment, with no known active disease and felt to be at low risk for recurrence by the treating physician, after discussion with the sponsor o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of dis-ease o adequately treated cervical cancer in situ without evidence of disease o adequately treated breast ductal carcinoma in situ without evidence of disease o prostatic intraepithelial neoplasia without evidence of prostate cancer o adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
8. - Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn’s disease], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc), autoimmune pneumonitis, and autoimmune myocarditis. The following are exceptions to this criterion: o Subjects with vitiligo or alopecia o Subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone re-placement o Any chronic skin condition that does not require systemic therapy o Subjects without active disease in the last 5 years may be included but only after consulta-tion with the sponsor o Subjects with coeliac disease controlled by diet alone
9. - Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II, appendix 2), within 6 months prior to first dose of study treatment
10. - History of arterial thrombosis (e.g. stroke or transient ischemic attack) within 6 months prior to first dose of study treatment
11. - Evidence of ILD or active, non-infectious pneumonitis
12. - History of solid organ transplant
13. - Major surgical procedures within 28 days prior to first dose of study treatment
14. - Presence of active HIV or hepatitis infection o HIV infection: subjects with HIV infection on antiviral therapy and undetectable viral load are permitted with a requirement for regular monitoring for reactivation for the duration of the treatment on study per local or institutional guidelines o Active hepatitis C infection (subjects with detectable hepatitis C antibody [HCV Ab] and hepatitis C virus (HCV) RNA viral load above the limit of quantification) are not allowed. Subjects with presence of HCV antibody (HCV Ab positive) and HCV RNA viral load below the limit of quantification (HCV RNA negative) with or without prior treatment are allowed o Active hepatitis B infection (subjects with presence of hepatitis B surface antigen [HBsAg-positive] and hepatitis B virus (HBV) DNA viral load above the limit of quantification [HBV DNA positive) are not allowed. Subjects with resolved HBV infection, defined as absence of HBV surface antigen (HBsAg-negative) and presence of HBV core antibody (anti-HBc posi-tive) followed by an HBV DNA viral load below the limit of quantification (HBV DNA nega-tive) are allowed with a requirement for regular monitoring for reactivation for the dura-tion of treatment on the study and assessing the need for HBV prophylaxis therapy per lo-cal or institutional guidelines. Subjects with inactive HBV infection inactive carrier state, de-fined as presence of HBV surface antigen (HBsAg-positive) and HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed with the requirement for regular monitoring for reactivation for the duration of the treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines.
15. - Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 14 days prior to first dose of study treatment o Low-dose corticosteroids (prednisone ≤ 10 mg per day or equivalent is permitted during the study) o Additionally, for CNS metastases specifically a maximum dose of steroids is 4 mg dexame-thasone or equivalent/day, dose should be noted.
16. - Subjects 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 study treat-ment o Note: simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. Subjects requiring oral antibiotics who have been afe-brile > 24 hours, have no leukocytosis, nor clinical signs of an infection are eligible. Screen-ing for chronic infectious conditions is not required unless otherwise noted as exclusion cri-teria.
17. - Treatment with live virus, including live-attenuated vaccination, within 4 weeks prior to the first dose of study treatment. Inactive vaccines (e.g. non-live or non-replication agent) and live viral non-replicating vaccines (e.g. Jynneos for mpox infection) within 30 days prior to first dose of study treatment
18. - Prior therapy with any selective inhibitor of the DLL3 pathway
19. - Receiving another anticancer therapy. Adjuvant hormonal therapy for resected breast cancer is permitted.
20. - Treatment in an alternative investigational trial within 28 days prior to enrollment
21. - Female subjects of childbearing potential unwilling to use protocol specified method of contracep-tion (appendix 3) during treatment and for an additional 60 days after the last dose of tarlatamab
22. - Female subjects who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of tarlatamab
23. - Female subjects planning to become pregnant or donate eggs while on study through 60 days after the last dose of tarlatamab
24. - Female subjects of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test
25. - Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 60 days after the last dose of tarlatamab
26. - 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
27. - Male subjects unwilling to abstain from donating sperm during treatment and for an additional 60 days after the last dose of tarlatamab
28. - Subject has known sensitivity to any of the products or components to be administered during dos-ing of tarlatamab.
29. - History or evidence of any other clinically significant disorder, condition or disease (with the excep-tion of those outlined above) that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
30. - Subjects likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigators knowledge.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - BM ORR (RANO-BM). This will be evaluated with MRI brain after six weeks of treatment and there-after every six weeks. Confirmed BM ORR according to RANO-BM will be measured at 12 weeks.

Secondary endpoints 1

1. All imaging related endpoints will be measured with MRI brain for BM related outcomes and CT chest and upper abdomen for extracranial related outcomes after six weeks of treatment and thereafter eve-ry six weeks. - Key secondary: BM DCR (RANO-BM), CNS PFS (RANO-BM) - Extracranial ORR and DCR (RECIST 1.1) - extracranial PFS (based on RECIST 1.1) - overall PFS (based on RANO-BM for BM and RECIST 1.1 for extracranial lesions) - OS - Safety according to CTCAE v 5.0 during every visit

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Maastricht

Sponsor organisation

Academisch Ziekenhuis Maastricht

Address

P Debyelaan 25

City

Maastricht

Postcode

6229 HX

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Maastricht

Contact name

Lizza Hendriks

Public contact point

Organisation

Academisch Ziekenhuis Maastricht

Contact name

Lizza Hendriks

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications