AMG 757 and AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)

Amgen

Status and phase: Completed; Phase 1

Conditions: Small Cell Lung Cancer

Treatments: Drug: Tarlatamab; Drug: AMG 404

Study type: Interventional

Funder types: Industry

Identifiers

NCT04885998

2020-005957-26 (EudraCT Number)

20200439

Details and patient eligibility

About

The main purpose of this study is to evaluate the safety, tolerability, and recommended phase 2 target dose of tarlatamab in combination with AMG 404.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures
• Age greater than or equal to 18 years old at the same time of signing the informed consent
• Participants with histologically or cytologically confirmed Small Cell Lung Cancer (SCLC) who progressed or recurred following at least 1 platinum-based regimen
• Eastern Cooperative Oncology Group (ECOG) 0 to 1
• Participants with treated brain metastases are eligible provided they meet defined criteria
• Adequate organ function as defined in protocol

Exclusion criteria

• History of other malignancy within the past 2 years with exceptions
• Major surgery within 28 days of first dose of tarlatamab
• Untreated or symptomatic brain metastases and leptomeningeal disease
• Prior anti-cancer therapy, including anti-PD1 or anti-PDL1 antibody therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and the first planned dose of tarlatamab

Exceptions:

• Participants who received prior chemotherapy must have completed at least 14 days before the first dose of tarlatamab and all treatment-related toxicity resolved to grade ≤ 1.

• Participants who received prior palliative radiotherapy must have completed at least 7 days before the first dose of tarlatamab

  • Participants who received prior tarlatamab therapy or prior delta-like ligand 3 (DLL3) x cluster of differentiation 3 (CD3) bispecific therapy are not eligible
  • 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
  • History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis
  • Participants with evidence of interstitial lung disease or active, non-infectious pneumonitis
  • 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 tarlatamab
  • History of solid organ transplantation
  • History of hypophysitis or pituitary dysfunction
  • 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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23 participants in 2 patient groups

Phase 1: Dose Exploration

Experimental group

Description:

The recommended phase 2 target dose (RP2D) of tarlatamab in combination with AMG 404 will be estimated using a modified toxicity probability interval (mTPI-2) design. A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).

Treatment:

Drug: AMG 404

Drug: Tarlatamab

Phase 2: Dose Expansion

Experimental group

Description:

Participants will receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1 (dose exploration) of the study.

Treatment:

Drug: AMG 404

Drug: Tarlatamab