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

A Phase 1 First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 355 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AMG 355; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 515
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Recruiting
      • The Queen Elizabeth Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
  • Kansas
    • Merriam, Kansas, United States, 66204
      • Recruiting
      • Alliance for Multispecialty Research Kansas City
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key 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. Additional indications may be explored in consultation with Medical Monitor.
  • Group B: NSCLC, CRC, GC. Additional indications may be explored in consultation with Medical Monitor.
• 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 must not be used 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: Samples must consist of a minimum of 10 (20 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, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: AMG 355 monotherapy; Specified dose on specified days	Drug: AMG 355; Short-term intravenous (IV) infusion
Experimental: Group B: AMG 355 and pembrolizumab; Specified dose on specified days	Drug: AMG 355; Short-term intravenous (IV) infusion; Drug: Pembrolizumab; Short-term IV infusion; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Up to 2 years
Number of Participants Who Experience a Treatment-related AE		Up to 2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Estimated): February 8, 2027
• Study Completion (Estimated): February 8, 2028

Study Registration Dates

• First Submitted: November 9, 2023
• First Submitted That Met QC Criteria: November 9, 2023
• First Posted (Actual): November 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Pembrolizumab; Advanced Solid Tumors; Gastric Cancer (GC); Colorectal Cancer (CRC); Melanoma (MEL); Non-small Cell Lung Cancer (NSCLC); AMG 355
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 20220028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No