Phase 3 Trial of Tarlatamab (SC vs IV) In Extensive-Stage Small Cell Lung Cancer After Platinum based First-line Chemotherapy (DeLLphi-315)

Prior treatment

• More than 1 prior line of anticancer therapy for SCLC
• Participation in a tarlatamab clinical trial or prior therapy with any selective inhibitor of the DLL3 pathway
• Treatment in an alternative investigational trial within 28 days prior to enrollment
• Major surgical procedures within 28 days prior to first dose of study treatment
• Prior history of severe or life-threatening events from any immune-mediated therapy
• Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 14 days prior to first dose of study treatment
• Has received any live virus or live-attenuated vaccine, or inactive (eg, non-live or non-replicating agent) or live viral non-replicating vaccines such as JYNNEOS® (Modified Vaccinia Ankara) within 28 days prior to the first dose of study treatment
• symptoms and/or clinical signs and/or radiographic findings that indicate an acute and/or uncontrolled active systemic infection within the 7 days prior to the first dose of study treatment
• Prior systemic anticancer therapy within 30 days of enrollment
• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 6 months prior to first dose of study treatment. Participants with known history of atrial fibrillation are allowed if they are clinically stable and controlled under treatment
• History of arterial thrombosis (eg, stroke, limb ischemia, renal or mesenteric ischemia) within 6 months prior to first dose of study treatment. Participants who have suffered a single event of TIA (transient ischemic attack) can be eligible if completely resolved without lasting damage
• Receiving another anticancer therapy for a malignancy other than SCLC.  Adjuvant hormonal therapy for resected breast cancer is permitted

Other illness

• History of other malignancy other than SCLC within the past 2 years prior to enrollment with the following exceptions:  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
• Presence or history of viral hepatitis infection
• History of solid organ transplant
• History of allergy or hypersensitivity to similar products (eg, drugs with a similar chemical structure or other monoclonal antibody) or any excipient
• History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety
• Participants with HIV infection on antiviral therapy and undetectable viral load (HIV RNA undetectable) are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on study per local or institutional guidelines
• Current evidence or history of non-infectious pneumonitis/ILD (interstitial lung disease) that required steroids or other immunosuppressive treatment

Lab values

• Previous diagnosis of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutation that has transformed to SCLC, or mixed SCLC and NSCLC histology.  Participants with mixed histology tumors with predominant SCLC histology are allowed provided the NSCLC component does not harbor an EGFR-activating mutation

Other

• Participant has known sensitivity or a contraindication to any of the products or components to be administered during dosing
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than 1 time per month
• Participants unable to have SC injections administered in the abdomen or thigh
• Participant unlikely to be able to complete all protocol-required procedures, restrictions and requirements, in the judgment of the individual and investigator

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Toxicities attributed to prior anticancer therapy resolved to grade ≤ 1, unless otherwise specified, excluding alopecia (any grade), fatigue grade ≤ 2, anemia grade ≤ 2 (hemoglobin ≥ 9 g/dL) and hypothyroidism grade ≤ 2 (in need of hormone replacement) considered to be related to chemo-immunotherapy prior to screening
• Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years)
• Histologically or cytologically confirmed small-cell lung carcinoma with demonstrated radiographic progression or relapse after only 1 platinum-based regimen Documented disease progression must be following first-line platinum-based systemic chemotherapy with or without anti-PD-(L)1 therapies for ES-SCLC. In countries where SOC first-line systemic treatment for ES-SCLC disease includes platinum containing chemotherapy in combination with PD-(L)1 inhibitor, it is required that patients have failed PD-(L)1 inhibitor as part of their first-line systemic treatment or are ineligible to receive PD-(L)1 inhibitor therapy Participants treated with a platinum-based regimen for LS-SCLC may be eligible if relapse of the disease is documented within the 6 months after last dose of platinum-based chemotherapy
• Measurable disease as defined per investigator according to RECIST 1.1 criteria within the 21-day screening period
• Participants with history of central nervous system (CNS) metastases are allowed provided the following considerations are met:  Participants with untreated asymptomatic brain metastases that do not require corticosteroids and/or anticonvulsants and according to investigator´s assessment do not require immediate local therapy are considered eligible.  Participants with treated brain metastases are eligible provided the following criteria are met:  Radiation treatment was completed at least 14 days prior to first dose of study treatment (stereotactic radiosurgery completed at least 7 days prior to first dose of study treatment).  Clinically stable, with grade ≤1 toxicities from radiation therapy and on stable or decreasing doses of corticosteroids (maximum total daily dose of 10 mg prednisone or equivalent) and/or anticonvulsants  Participants have not been diagnosed with leptomeningeal carcinomatosis
• Available archival tumor tissue from diagnosis. If archival tumor tissue samples are unavailable, a new biopsy should be obtained during the screening period and submitted. Participants who do not have sufficient archived tissue and for whom a biopsy cannot be safely performed may be permitted to enroll if rationale for not providing tumor tissue is clearly documented by the treating investigator (eg, document unacceptable medical risks of all locations of disease considered for biopsy if pursued for a prospective participant).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Minimum life expectancy of 12 weeks as per investigator judgement
• Adequate organ function, defined as follows: Refer to protocol section 5.2 for more details - Hematological function: - Coagulation function: - Renal function: - Hepatic function: - Pulmonary function: - Cardiac function: