| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed/Refractory Small Cell Lung Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Relapsed/Refractory Small Cell Lung Cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10041070 |
| E.1.2 | Term | Small cell lung cancer recurrent |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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 |
|
| E.2.2 | Secondary objectives of the trial |
•Evaluate anti-tumor activity of Tarlatamab as determined by other measures per RECIST 1.1 by BICR
•Evaluate anti-tumor activity of Tarlatamab as assessed by ORR and other measures per RECIST 1.1 by investigator
•Evaluate the safety and tolerability of Tarlatamab
•Characterize the pharmacokinetics (PK) of Tarlatamab
•Evaluate the immunogenicity of Tarlatamab |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
101 Subject has provided informed consent/assent prior to initiation of any study
specific activities/procedures.
102 Male and female subjects >= 18 years of age (or legal adult age within country) at the time of signing the informed consent.
103 Histologically or cytologically confirmed relapsed/refractory SCLC
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.
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.
106 Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
107 Minimum life expectancy of 12 weeks.
108 Measurable lesions as defined per RECIST 1.1 within 21 days prior to the first
dose of Tarlatamab.
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.
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 |
|
| E.4 | Principal exclusion criteria |
Disease Related
201 Untreated or symptomatic brain metastases and leptomeningeal disease.
202 Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
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.
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 day) 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.
Other Medical Conditions
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.
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).
207 History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of Tarlatamab.
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 (UTI) 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.
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.
210 History of hypophysitis or pituitary dysfunction.
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
212 Major surgery within 28 days of first dose Tarlatamab.
213 History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Subject is eligible if no acute symptoms of coronavirus disease 2019 (COVID-19) within 14 days prior to first dose of Tarlatamab (counted from day of positive test for asymptomatic subjects)
Prior/Concomitant Therapy
214 Subject received prior therapy with Tarlatamab.
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.
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.
217 Live and live-attenuated vaccines within 4 weeks prior to the start of Tarlatamab treatment.
Please refer to protocol for exclusion criteria 217 to 228. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1 only
•objective response (OR) (complete response [CR] and partial response [PR])
•incidence of treatment-emergent adverse events (TEAEs)
•serum concentrations of Tarlatamab
Part 1 and 2
•OR (CR and PR)
Part 3
•Incidence of TEAEs |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis is planned when all subjects have been enrolled and have had the opportunity to have at least 6 months of follow up from the first post-baseline tumor assessment.
The final analysis will occur when enrollment is complete and each subject completes the study, including long-term follow up. |
|
| E.5.2 | Secondary end point(s) |
•duration of response (DOR)
•disease control (DC)
•duration of DC
•progression-free survival (PFS)
•DOR
•overall survival (OS)
•incidence of TEAEs
•serum concentrations of Tarlatamab
•incidence of anti-Tarlatamab antibody formation |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
The primary analysis is planned when all subjects have been enrolled and have had the opportunity to have at least 6 months of follow up from the first post-baseline tumor assessment.
The final analysis will occur when enrollment is complete and each subject completes the study, including long-term follow up. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 42 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Japan |
| Korea, Republic of |
| Singapore |
| Taiwan |
| United States |
| Switzerland |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
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