A Study of SGN-EGFRd2 in Advanced Solid Tumors

Study Overview
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Brief Summary
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This study will test the safety of a drug called SGN-EGFRd2 in participants with advanced solid tumors. It will also study the side effects of this drug. A side effect is anything a drug does to the body besides treating the disease. Participants will have cancer that cannot be removed (unresectable) or has spread through the body (metastatic). This study will have three parts. Parts A and B of the study will find out how much SGN-EGFRd2 should be given to participants. Part C will use the dose found in parts A and B to find out how safe SGN-EGFRd2 is and if it works to treat solid tumor cancers.

Official Title
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A Phase 1 Study of SGN-EGFRd2 in Advanced Solid Tumors

Conditions
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Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of the Head and Neck, Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: SGN-EGFRd2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Tumor types: For Part A: Participants must have disease that is relapsed, refractory, or be intolerant to standard of care therapies, and in the judgement of the investigator must have no appropriate standard therapy available at the time of enrollment. Participants must have histologically- or cytologically confirmed metastatic or unresectable solid malignancy from one of the following tumor types: Colorectal cancer (CRC) Non-small cell lung cancer (NSCLC) Head and neck squamous cell cancer (HNSCC) For Part B: Participants must have disease that is relapsed, refractory, or be intolerant to standard of care therapies, and in the judgement of the investigator must have no appropriate standard therapy available at the time of enrollment. The tumor type(s) to be enrolled in dose optimization will be identified by the sponsor from among those specified in Part A. For Part C: Participants must have disease that is relapsed or refractory or be intolerant to standard of care therapies as specified below, unless contraindicated: CRC Participants must have unresectable locally advanced or metastatic CRC. Prior therapy: Participants must have received prior fluoropyrimidine, oxaliplatin and irinotecan. Participants with defective mismatch repair and microsatellite instability high (dMMR/MSI-H) should have received prior treatment with pembrolizumab, a nivolumab-containing regimen, or other available anti-PD-1 (programmed cell death protein 1) or anti PD L1 (programmed cell death 1 ligand) agents. NSCLC Participants must have unresectable locally advanced or metastatic NSCLC. Prior therapy: Participants must have received platinum-based therapy and at least 1 PD-1/PD-L1 inhibitor. These agents may have been administered either as single agents or in combination. Participants with an activating mutation or rearrangement (eg, EGFR, anaplastic lymphoma kinase [ALK], etc.) must have received available targeted agents if eligible by biomarker status and local standard of care. HNSCC Participants must have unresectable locally advanced or metastatic HNSCC Prior therapy: Participants must have received platinum-based therapy and a PD-1/PD-L1 inhibitor, if eligible by biomarker status and local standard of care. These agents may have been administered either as single agents or in combination. Pancreatic ductal adenocarcinoma (PDAC) Participants must have unresectable locally advanced or metastatic PDAC. Prior therapy: Participants must have received gemcitabine- or FOLFIRINOX-based therapy. Participants should provide archival tumor tissue if available and also agree to biopsies, if medically feasible An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. Measurable disease at baseline per RECIST 1.1 criteria. Exclusion Criteria: History of another malignancy within 3 years before the first dose of study treatment, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death Known active central nervous system metastases or leptomeningeal disease. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry after brain metastases treatment, they have no new or enlarging brain metastases, and are off of corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study drug. Treatment with an aminobisphosphonate IV (eg ibandronate, pamidronate, zoledronate, etc.) within 4 weeks of the first dose of study treatment. Participants with history of thromboembolic phenomena (pulmonary embolism, deep vein thrombosis, stroke, or ischemic attack) within 6 months prior to the first dose of study drug, currently receiving chronic anticoagulation therapy, or with contraindication to treatment for thromboembolism prophylaxis.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGN-EGFRd2<br>SGN-EGFRd2 monotherapy | Drug: SGN-EGFRd2<br>* Given into the vein (IV; intravenously)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention | Through 90 days after last study treatment, up to approximately 1 year | 
| Number of participants with laboratory abnormalities |  | Through 30-37 days after last study treatment, up to approximately 1 year | 
| Number of participants with dose limiting toxicities (DLTs) |  | Up to 35 days | 
| Number of participants with DLTs by dose level |  | Up to 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with antidrug antibodies (ADAs) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, up to approximately 1 year | 
| Pharmacokinetic (PK) parameter - Area under the curve (AUC) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, up to approximately 1 year | 
| PK parameter - Maximum concentration (Cmax) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, up to approximately 1 year | 
| PK parameter - Time to maximum concentration (Tmax) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, up to approximately 1 year | 
| PK parameter - Apparent terminal half-life (t1/2) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, up to approximately 1 year | 
| PK parameter - Trough concentration (Ctrough) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, up to approximately 1 year | 
| Objective response rate (ORR) | ORR is defined as the proportion of participants with an objective response per Response Evaluation in Solid Tumors (RECIST) 1.1 per investigator. A participant is determined to have an objective response if, based on RECIST 1.1, they achieve a complete response (CR) or partial response (PR) after initiation of treatment and at or prior to the EOT disease assessment. | Up to approximately 2 years | 
| Duration of response (DOR) | DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per RECIST 1.1 or to death due to any cause, whichever comes first | Up to approximately 2 years | 
| Progression-free survival (PFS) | PFS is defined as the time from start of SGN-EGFRd2 to first documentation of disease progression or death due to any cause, whichever comes first | Up to approximately 2 years | 
| Overall survival (OS) | OS is defined as the time from start of SGN-EGFRd2 to date of death due to any cause | Up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRC, Colon Cancer, Rectal Cancer, NSCLC, HNSCC, PDAC, Seattle Genetics