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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: AMG 355
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Overall Survival |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumors, AMG 355, Pembrolizumab, Pharmacokinetics, Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Gastric Cancer (GC), Melanoma (MEL)