Clinical trial NCT06131398: A Study of AMG 355 Alone and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced Solid Tumors
AMG 355
Pembrolizumab
Pharmacokinetics
Non-small Cell Lung Cancer (NSCLC)
Colorectal Cancer (CRC)
Gastric Cancer (GC)
Melanoma (MEL)
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2023-11-14
Enrollment: 535
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.
  * 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.

Primary outcomes:
measure: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
timeFrame: Day 1 to Day 21
measure: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Up to 2 years
measure: Number of Participants Who Experience a Treatment-related AE
timeFrame: Up to 2 years
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of AMG 355
timeFrame: Up to 85 days
measure: Minimum Observed Serum Concentration (Cmin) of AMG 355
timeFrame: Up to 85 days
measure: Area Under the Concentration-time Curve (AUC) of AMG 355
timeFrame: Up to 85 days
measure: Confirmed Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
timeFrame: Up to 2 years
measure: Clinical Benefit per RECIST v1.1
timeFrame: Up to 2 years
measure: Duration of Response per RECIST v1.1
timeFrame: Up to 2 years
measure: Time to Progression by RECIST v1.1
timeFrame: Up to 2 years
measure: Progression-free Survival (PFS) by RECIST v1.1
timeFrame: Up to 2 years
measure: Overall Survival
timeFrame: Up to 2 years
measure: Change From Baseline in C-C motif chemokine receptor 8 (CCR8+) Expression Between Pre and On Treatment Tumor Samples
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Merriam
country: United States
facility: Alliance for Multispecialty Research - Kansas City
state: Kansas
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Darlinghurst
country: Australia
facility: St Vincents Hospital Sydney
state: New South Wales
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Bordeaux
country: France
facility: Institut Bergonie
city: Villejuif
country: France
facility: Gustave Roussy
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
city: St. Gallen
country: Switzerland
facility: Kantonsspital Sankt Gallen
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: