AVID100 in Advanced Epithelial Carcinomas

Study Overview
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Brief Summary
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Approximately 90 male and female patients with documented solid tumor malignancies of epithelial origin that are locally advanced or metastatic, and either refractory to standard therapy or for whom no standard therapy is available, will be entered into this Phase 1a/2a, multicenter, open-label, dose-escalation, cohort study of AVID100. Phase 2a will include evaluation of patient with EGFR-overexpressing squamous histology non-small cell lung cancer, squamous cell carcinoma of the head and neck, and triple negative breast cancer

Detailed Description
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On Day 1 of study, patients will receive study drug administered by 2-hour IV infusion. AVID100 will be administered once every 3 weeks (Q3W) with administration on Day 1 of the first week, followed by a 3-week recovery period. In Phase 2a AVID100 will be administered at a dose of 220 mg/m2. Evidence of progressive disease at any point in the study will necessitate withdrawal of the patient from further participation so that alternative management of their malignancy may be considered. All patients will be followed to further evaluate safety as well as evidence of the anti-tumor effects of AVID100 in these selected patient populations. If anti-tumor activity is observed additional patients may be added to the planned Phase 2a patient populations to further characterize these effects.

Official Title
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Phase 1a/2a Dose Escalation Trial to Determine Safety, Tolerance, MTD, and Preliminary Antineoplastic Activity of AVID100, in Patients With Advanced or Metastatic Solid Tumors of Epithelial Origin

Conditions
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Solid Tumor, Adult, Triple Negative Breast Cancer, Head and Neck Squamous Cell Carcinoma, Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: AVID100 IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Phase 1): Patients with a documented (histologically- or cytologically-proven) solid tumor epithelial carcinoma that is locally advanced or metastatic Patients with a malignancy that is either refractory to standard therapy, or for which no standard therapy is available Patients with a malignancy that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor Phase 1a Dose-Escalation Cohorts: Patients with measurable or non-measurable disease according to RECIST, v1.1 criteria. To include patients reasonably likely to express EGFR. Inclusion Criteria (Phase 2a) Patients with measurable disease according to RECIST, v1.1 criteria. Patients with triple negative breast cancer who are either EGFR 2+ or EGFR 3+ by validated IHC assay. Patients with squamous non-small cell lung cancer who are EGFR 3+ by validated IHC assay. Patients with squamous cell carcinoma of the head and neck who are EGFR 3+ by validated IHC assay. Patients whose malignancy is either refractory to standard therapy, or for which no standard therapy is available Patients whose malignancy is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor Patients to be Excluded (patients must not meet any of the following criteria Phase 1 only) Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a medically effective method of contraception. Patients with known central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required Patients with a malignancy other than that of epithelial origin Patients with hematologic abnormalities at baseline Patients with a significant cardiovascular disease or condition Patients with a significant ocular disease or condition Patients with a significant pulmonary disease or condition History of pneumonia within 6 months prior to the first study drug administration Patients with significant gastrointestinal (GI) abnormalities Patients with non-healing wounds on any part of the body Patients to be Excluded (patients must not meet any of the following criteria Phase 2a only) Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a medically effective method of contraception. Patients with known central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required Patients with a malignancy other than EGFR-overexpressing triple negative breast cancer, squamous histology non-small cell lung cancer, or squamous cell carcinoma of the head and neck. Patients with hematologic abnormalities at baseline Patients with a significant cardiovascular disease or condition Patients with a significant ocular disease or condition Patients with a significant pulmonary disease or condition History of pneumonia within 6 months prior to the first study drug administration Patients with significant gastrointestinal (GI) abnormalities Patients with non-healing wounds on any part of the body Patients without measurable disease according to RECIST v1.1 Patients with an active second malignancy within the last 2 years prior to entry Drugs and Other Treatments to be Excluded Any antineoplastic agent for the primary malignancy (standard or investigational), without delayed toxicity, within 4 weeks, 5 plasma half-lives, or twice the duration of the biological effect, whichever is shortest, prior to first study drug administration and during study with the exception of: Nitrosoureas and nitrogen mustard within 6 weeks prior to first study drug administration and during study Any other investigational treatments during study. This includes participation in any medical device or other therapeutic intervention clinical trials. Radiotherapy for target lesions within 4 weeks prior to first study drug administration and during study Herbal preparations or related over-the-counter (OTC) preparations/supplements containing herbal ingredients aimed at treating the underlying malignancy within 2 weeks prior to first study drug administration and during study Strong inhibitors and/or inducers of cytochrome P450 (CYP) isoenzyme 3A4 within 2 weeks prior to first study drug administration and during study Immunosuppressive or systemic hormonal therapy within 2 weeks prior to first study drug administration and during study. Prophylactic use of hematopoietic growth factors within 1 week prior to first study drug administration and during Cycle 1 of study; thereafter prophylactic use of growth factors is allowed as clinically indicated

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Uncontrolled, open label, non-randomized, Enrollment in the order of confirmation of eligibility, Escalating doses of study drug in sequential patient cohorts (Phase 1a). Uncontrolled, open label, non-randomised. Enrollment into three individual Phase 2a study cohorts
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>Minimum of 1 to 3 patients per dose cohort; approximately 4 dose cohorts to be evaluated to establish the Maximum tolerated dose. | Drug: AVID100 IV<br>* AVID100 is administered once every 3 weeks<br>|
| Experimental: Phase 2a Triple Negative Breast Cancer<br>Addition of up to 15 patients in each of 2 subpopulations of patients with triple negative breast cancer (30 total). One group of 15 patients will have 3+ EGFR over-expression. The second group will have 2+ EGFR over-expression. | Drug: AVID100 IV<br>* AVID100 is administered once every 3 weeks<br>|
| Experimental: Phase 2a Head and Neck Carcinoma<br>Addition of 15 patients with squamous head and neck carcinoma. Patients will have 3+ EGFR over-expression. | Drug: AVID100 IV<br>* AVID100 is administered once every 3 weeks<br>|
| Experimental: Phase 2a Non-Small Cell Lung Carcinoma<br>Addition of 15 patients with squamous histology non-small cell lung carcinoma. Patients will have 3+ EGFR over-expression | Drug: AVID100 IV<br>* AVID100 is administered once every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a: Determine safety and tolerability of AVID100 | Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment | 6 months | 
| Phase 2a: Evaluation of the preliminary antineoplastic effects of AVID100 | Number of participants with objective response or stable disease | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Profile of Total Antibody | Characterization of the pharmacokinetic profile of total antibody | 18 months |