This is a phase 1b study to assess the safety and tolerability of tarlatamab in combination with programmed death ligand (PD-L1) inhibition with and without chemotherapy

JRCT ID: jRCT2031220277

Registered date:18/08/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Extensive Stage Small Cell Lung Cancer
• Date of first enrollment: 24/08/2022
• Target sample size: 340
• Countries of recruitment: United States,Japan,Australia,Japan,Belgium,Japan,Canada,Japan,France,Japan,Germany,Japan,Korea,Japan,Spain,Japan,Switzerland,Japan,Denmark,Japan,Israel,Japan,Italy,Japan,Netherlands,Japan,Taiwan,Japan
• Study type: Interventional

Intervention(s)

- Experimental: Part 1: Dose Exploration Combination Regimen 1
Tarlatamab+Atezolizumab+Carboplatin+Etoposide
Interventions:
- Drug: Tarlatamab
- Drug: Carboplatin
- Drug: Etoposide
- Drug: Atezolizumab

- Experimental: Part 2: Dose Exploration Combination Regimen 2
Tarlatamab+Atezolizumab+Carboplatin+Etoposide
Interventions:
- Drug: Tarlatamab
- Drug: Carboplatin
- Drug: Etoposide
- Drug: Atezolizumab

- Experimental: Part 3: Dose Exploration Combination Regimen 3
Tarlatamab+Atezolizumab+Carboplatin+Etoposide
Interventions:
- Drug: Tarlatamab
- Drug: Carboplatin
- Drug: Etoposide
- Drug: Atezolizumab

- Experimental: Part 4: Dose Expansion
Expansion of Part 1, Part 2, or Part 3 with Atezolizumab
Interventions:
- Drug: Tarlatamab
- Drug: Carboplatin
- Drug: Etoposide
- Drug: Atezolizumab

- Experimental: Part 5: Dose Exploration Maintenance
Tarlatamab+Atezolizumab
Interventions:
- Drug: Tarlatamab
- Drug: Carboplatin
- Drug: Etoposide
- Drug: Atezolizumab

- Experimental: Part 6: Dose Expansion Maintenance
Expansion of Part 5 with Atezolizumab
Interventions:
- Drug: Tarlatamab
- Drug: Carboplatin
- Drug: Etoposide
- Drug: Atezolizumab

- Experimental: Part 7: Dose Expansion
Expansion of Part 1, 2, or 3 with Durvalumab
Interventions:
- Drug: Tarlatamab
- Drug: Carboplatin
- Drug: Etoposide
- Drug: Durvalumab

- Experimental: Part 8: Dose Expansion Maintenance
Expansion of Part 5 with Durvalumab
Interventions:
- Drug: Tarlatamab
- Drug: Durvalumab

- Experimental: Part 9: Dose Expansion Maintenance
Expansion with Tarlatamab+Durvalumab
Interventions:
- Drug: Tarlatama
- Drug: Durvalumab

Outcome(s)

Primary Outcome

1. Number of Participants with a Dose Limiting Toxicity (DLT) [ Time Frame: 24 months ]
2. Number of Participants with Treatment-emergent Adverse Events (TEAE) [ Time Frame: 24 months ]
3. Number of Participants with Treatment-related Adverse Events [ Time Frame: 24 months ]
4. Number of Participants with Clinically Significant Changes in Vital Signs [ Time Frame: 24 months ]
5. Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Measurements[ Time Frame: 24 months ]
6. Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [ Time Frame: 24 months ]

Secondary Outcome

1. 6-month Progression-free Survival (PFS) [ Time Frame: 24 months ]
2. Objective Response (OR) [ Time Frame: 24 months ]
Per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
3. Duration of Response (DOR) [ Time Frame: 24 months ]
4. Disease Control Rate(DCR) [ Time Frame: 24 months ]
5. Overall Survival (OS) [ Time Frame: 24 months ]
6. Serum Concentration of Tarlatamab [ Time Frame: 24 months ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Participant has provided informed consent prior to initiation of any study specific activities/procedures.
2. Age greater than or equal to 18 years old at the same time of signing the informed consent.
3. Histologically or cytologically confirmed Extended Stage Small Cell Lung Cancer (ES-SCLC) and no prior systemic treatment for ES-SCLC.
4. Participants with prior treatment for limited-stage SCLC (LS-SCLC) are permitted.
5. Eastern Cooperative Oncology Group (ECOG) 0 to 1.
6. Participants with treated asymptomatic brain metastases are eligible provided they meet defined criteria.
7. Adequate organ function as defined in protocol.

Exclude criteria

1. History of other malignancy within the past 2 years with exceptions.
2. Major surgery within 28 days of study day 1.
3. Untreated or symptomatic brain metastases and leptomeningeal disease.
4. Participants who experienced recurrent grade 2 pneumonitis or severe or life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.
5. History of immune-related colitis.
6. History or evidence of interstitial lung disease or active, non-infectious pneumonitis.
7. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
8. History of solid organ transplantation.
9. History of hypophysitis or pituitary dysfunction.
10. History of solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
11. Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type I diabetes, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted.

Related Information

• Primary Sponsor: Tagashira Shuzo
• Secondary ID(s): NCT05361395