A Phase 2 Study of Tarlatamab in Patients with Small Cell Lung Cancer (SCLC).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Dec 2021 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Amgen Inc.

External identifiers

EU CT number

2024-511837-37-00

EudraCT number

2021-002566-40

WHO UTN

U1111-1310-7798

ClinicalTrials.gov

NCT05060016

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Dose response

Part 1 only
To evaluate safety and efficacy (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1] by investigator) of 2 dose levels of tarlatamab.
Parts 1 and 2
Evaluate anti-tumor activity of tarlatamab as determined by objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR)
Part 3
Evaluate safety of reduced mandatory monitoring period in cycle 1 at selected dose of tarlatamab

Secondary objectives 5

1. Evaluate anti-tumor activity of Tarlatamab as determined by other measures per RECIST 1.1 by BICR
2. Evaluate anti-tumor activity of Tarlatamab as assessed by ORR and other measures per RECIST 1.1 by investigator
3. Characterize the pharmacokinetics (PK) of Tarlatamab
4. Evaluate the immunogenicity of Tarlatamab
5. Evaluate the safety and tolerability of Tarlatamab

Conditions and MedDRA coding

Relapsed/Refractory Small Cell Lung Cancer

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 101 Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
2. 102 Male and female subjects >= 18 years of age (or legal adult age within country) at the time of signing the informed consent.
3. 103 Histologically or cytologically confirmed relapsed/refractory SCLC
4. 104 Subjects who progressed or recurred following 1 platinum-based regimen and at least 1 other prior line of therapy Note: (1) re-treatment with a platinum-based regimen is considered a second line of therapy; (2) platinum-based regimen followed by checkpoint inhibitor/anti-programmed death ligand 1 (PD-L1) as maintenance therapy is considered 1 line of therapy; (3) in countries where standard of care first line systemic treatment includes platinum containing chemotherapy in combination with PD-L1 inhibitor, it is required that patients have failed PD-L1 inhibitor as part of their first line systemic treatment or are ineligible to receive PD-L1 inhibitor therapy.
5. 105 Subjects willing to provide archived tumor tissue samples (formalin fixed, paraffin embedded [FFPE] sample) or willing to undergo pretreatment tumor biopsy. Subjects who do not have archived tumor tissue available and are unable to undergo a pretreatment tumor biopsy due to extenuating circumstances (eg, cannot be performed safely or inaccessible, as determined by the investigator) may be allowed to enroll without a tumor biopsy upon agreement between the investigator and Amgen medical monitor.
6. 106 Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
7. 107 Minimum life expectancy of 12 weeks.
8. 108 Measurable lesions as defined per RECIST 1.1 within 21 days prior to the first dose of Tarlatamab.
9. 109 Subjects with treated brain metastases are eligible provided they meet the following criteria: - Definitive therapy was completed at least 2 weeks prior to the first dose of Tarlatamab. - There is no evidence of radiographic central nervous system (CNS) progression following definitive therapy and by the time of study screening. Patients manifesting progression in lesions previously treated with stereotactic radiosurgery may still be eligible if pseudoprogression can be demonstrated by appropriate means and after discussion with the medical monitor. - Any CNS disease is asymptomatic for at least 7 days (unless symptoms are deemed irreversible by the investigator), the patient is off steroids 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.
10. 110 Adequate organ function, defined as follows: hematological function: - absolute neutrophil count >= 1 x 10^9/L - platelet count >= 100 x 10^9/L - hemoglobin > 9 g/dL (90 g/L) coagulation function: - prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) <= 1.5 x institutional upper limit of normal (ULN). Subjects on chronic anticoagulation therapy who do not meet the criteria above may be eligible to enroll after discussion with the medical monitor. renal function: - estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) calculation > 30 mL/min/1.73 m2 hepatic function: - aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) < 3 X ULN (or < 5 X ULN for subjects with liver involvement) - total bilirubin < 1.5 X ULN (or < 2 X ULN for subjects with liver metastases). pulmonary function: - no clinically significant pleural effusion - baseline oxygen saturation > 90% on room air cardiac function: - cardiac ejection fraction >= 50%, no clinically significant pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no clinically significant electrocardiogram (ECG) findings

Exclusion criteria 16

1. 201 Untreated or symptomatic brain metastases and leptomeningeal disease.
2. 210 History of hypophysitis or pituitary dysfunction.
3. 211 Exclusion of hepatitis infection based on the following results and/or criteria: - Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis 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. - Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C
4. 212 Major surgery within 28 days of first dose Tarlatamab.
5. 214 Subject received prior therapy with Tarlatamab.
6. 215 Prior anti-cancer therapy within 28 days prior to first dose of Tarlatamab. Exceptions: - 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. - Prior palliative radiotherapy must have been completed at least 7 days before the first dose of Tarlatamab.
7. 216 Has a diagnosis of immunodeficiency (e.g. positive/non-negative test for human immunodeficiency virus) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of Tarlatamab.
8. 202 Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
9. 203 Subjects who experienced recurrent pneumonitis (grade 2 or higher) or severe, life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.
10. 204 Unresolved toxicity from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1, or to levels dictated in the eligibility criteria with the exception of alopecia or toxicities from prior anti-tumor therapy that are considered irreversible(defined as having been present and stable for > 21 days) which may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and Amgen.
11. 205 History of other malignancy within the past 2 years, with the following exceptions: - malignancy treated with curative intent and with no known active disease present for >= 2 years before enrollment and felt to be at low risk for recurrence by the treating physician. - adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. - adequately treated cervical carcinoma in situ without evidence of disease. - adequately treated breast ductal carcinoma in situ without evidence of disease. - prostatic intraepithelial neoplasia without evidence of prostate cancer. - adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
12. 206 Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of Tarlatamab (Section 11.9).
13. 207 History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of Tarlatamab.
14. 208 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 and after consultation with sponsor. 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.
15. 209 Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or peritoneal/pericardial catheter). NOTE: A pleural catheter or dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted.
16. Please refer to protocol for exclusion criteria 217 to 238.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part 1 only - objective response (OR) (complete response [CR] and partial response [PR]) •incidence of treatment-emergent adverse events (TEAEs) •serum concentrations of Tarlatamab
2. Part 1 and 2 - OR (CR and PR)
3. Part 3 - Incidence of TEAEs

Secondary endpoints 9

1. duration of response (DOR)
2. disease control (DC)
3. duration of DC
4. progression-free survival (PFS)
5. DOR
6. overall survival (OS)
7. incidence of TEAEs
8. serum concentrations of Tarlatamab
9. incidence of anti-Tarlatamab antibody formation

Investigational products

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

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1730

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 14

Locations

9 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 81 files

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

Application history

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