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A Study of AMG 355 Alone and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

Phase 1
Recruiting
Conditions
Advanced Solid Tumors
Interventions
Registration Number
NCT06131398
Lead Sponsor
Amgen
Brief Summary

The primary objectives of this study are to:

* Evaluate the safety and tolerability of AMG 355 as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors

* Determine the recommended phase 2 dose and the maximum tolerated dose for AMG 355 as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
535
Inclusion Criteria
  • Age ≥ 18 years at the time of signing informed consent.

  • Participants with histologically or cytologically confirmed metastatic or locally advanced solid tumors who have relapsed after and/or are refractory to or ineligible for established and available therapies with known clinical benefit at time of pre-screening:

    • Group A: NSCLC, CRC, GC, and melanoma.
    • Group B: NSCLC, CRC, GC.
  • Eastern Cooperative Oncology Group Performance status 0 or 1.

  • Life expectancy of > 3 months, in the opinion of the investigator.

  • At least 1 measurable lesion as defined by modified RECIST 1.1 guidelines. Note: this lesion should be avoided for the required biopsies on the study.

  • Participants must be willing to undergo 1 or more biopsies as follows:

    • Fresh biopsy prior to enrollment is preferred or, if fresh tissue is not obtainable, an archival tumor sample may be acceptable if the sample was obtained within 6 months of enrollment and participant has not received any other treatment since sample was obtained, consult the Medical Monitor.
    • Mandatory fresh biopsy during cycle 2 (before the restaging of CT-scan) of treatment with AMG 355 (± pembrolizumab).

Note: Where slides are accepted, samples must consist of a minimum of 11 (21 preferred) freshly-cut, serially, sectioned, unstained slides. A formalin-fixed, paraffin embedded block is preferred if available, but in lieu of a block, unstained slides or fresh wet tissue is acceptable.

Key

Exclusion Criteria
  • Participant who received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137), and was discontinued from that treatment due to an immune-related adverse events.
  • Untreated or symptomatic brain metastases and leptomeningeal disease Note: participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Chronic intake of systemic corticosteroids (eg prednisone > 10 mg/day or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine or insulin) is not considered a form of systemic treatment and is allowed.
  • History of organ transplantation.
  • History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • 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.

Other protocol-defined inclusion/exclusion criteria apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Group A: AMG 355 monotherapyAMG 355Specified dose on specified days
Group B: AMG 355 and pembrolizumabAMG 355Specified dose on specified days
Group B: AMG 355 and pembrolizumabPembrolizumabSpecified dose on specified days
Primary Outcome Measures
NameTimeMethod
Number of Participants Who Experience a Dose Limiting Toxicity (DLT)Day 1 to Day 21
Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)Up to 2 years

Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests, as assessed by the investigator, will also be reported as TEAEs.

Number of Participants Who Experience a Treatment-related AEUp to 2 years
Secondary Outcome Measures
NameTimeMethod
Area Under the Concentration-time Curve (AUC) of AMG 355Up to 85 days
Clinical Benefit per RECIST v1.1Up to 2 years
Confirmed Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).Up to 2 years
Duration of Response per RECIST v1.1Up to 2 years
Time to Progression by RECIST v1.1Up to 2 years
Maximum Observed Serum Concentration (Cmax) of AMG 355Up to 85 days
Progression-free Survival (PFS) by RECIST v1.1Up to 2 years
Overall SurvivalUp to 2 years
Change From Baseline in C-C motif chemokine receptor 8 (CCR8+) Expression Between Pre and On Treatment Tumor SamplesUp to 2 years
Minimum Observed Serum Concentration (Cmin) of AMG 355Up to 85 days

Trial Locations

Locations (25)

City of Hope National Medical Center

🇺🇸

Duarte, California, United States

Alliance for Multispecialty Research - Kansas City

🇺🇸

Merriam, Kansas, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Wake Forest University Health Sciences

🇺🇸

Winston-Salem, North Carolina, United States

South Texas Accelerated Research Therapeutics

🇺🇸

San Antonio, Texas, United States

St Vincents Hospital Sydney

🇦🇺

Darlinghurst, New South Wales, Australia

The Queen Elizabeth Hospital

🇦🇺

Woodville South, South Australia, Australia

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Institut Bergonie

🇫🇷

Bordeaux, France

Gustave Roussy

🇫🇷

Villejuif, France

National Cancer Center Hospital East

🇯🇵

Kashiwa-shi, Chiba, Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

🇯🇵

Koto-ku, Tokyo, Japan

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Radboud Universitair Medisch Centrum

🇳🇱

Nijmegen, Netherlands

Erasmus Medisch Centrum

🇳🇱

Rotterdam, Netherlands

Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

🇵🇱

Warszawa, Poland

Hospital Universitari Vall d Hebron

🇪🇸

Barcelona, Cataluña, Spain

Hospital Clinic i Provincial de Barcelona

🇪🇸

Barcelona, Cataluña, Spain

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

Istituto Oncologico della Svizzera Italiana

🇨🇭

Bellinzona, Switzerland

Kantonsspital St Gallen

🇨🇭

St. Gallen, Switzerland

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

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