AVID100 in Advanced Epithelial Carcinomas

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

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

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer; Triple Negative Breast Cancer; Head and Neck Squamous Cell Carcinoma; Solid Tumor, Adult
• Intervention / Treatment: Drug: AVID100 IV

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Start Midwest
  • New York
    • New York, New York, United States, 10029
      • The Tisch Cancer Institute-Mt. Sinai
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology Midtown
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor -Charles A. Sammons Cancer Center
    • McAllen, Texas, United States, 78503
      • Texas Oncology McAllen
    • San Antonio, Texas, United States, 78217
      • Texas Oncology NE San Antonio
    • Tyler, Texas, United States, 75702
      • Texas Oncology Tyler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (Phase 1):

1. Patients with a documented (histologically- or cytologically-proven) solid tumor epithelial carcinoma that is locally advanced or metastatic
2. Patients with a malignancy that is either refractory to standard therapy, or for which no standard therapy is available
3. Patients with a malignancy that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor
4. 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)

1. Patients with measurable disease according to RECIST, v1.1 criteria.
2. Patients with triple negative breast cancer who are either EGFR 2+ or EGFR 3+ by validated IHC assay.
3. Patients with squamous non-small cell lung cancer who are EGFR 3+ by validated IHC assay.
4. Patients with squamous cell carcinoma of the head and neck who are EGFR 3+ by validated IHC assay.
5. Patients whose malignancy is either refractory to standard therapy, or for which no standard therapy is available
6. 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)

1. 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.
2. 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
3. Patients with a malignancy other than that of epithelial origin
4. Patients with hematologic abnormalities at baseline
5. Patients with a significant cardiovascular disease or condition
6. Patients with a significant ocular disease or condition
7. Patients with a significant pulmonary disease or condition
8. History of pneumonia within 6 months prior to the first study drug administration
9. Patients with significant gastrointestinal (GI) abnormalities
10. 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)

1. 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.
2. 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
3. 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.
4. Patients with hematologic abnormalities at baseline
5. Patients with a significant cardiovascular disease or condition
6. Patients with a significant ocular disease or condition
7. Patients with a significant pulmonary disease or condition
8. History of pneumonia within 6 months prior to the first study drug administration
9. Patients with significant gastrointestinal (GI) abnormalities
10. Patients with non-healing wounds on any part of the body
11. Patients without measurable disease according to RECIST v1.1
12. Patients with an active second malignancy within the last 2 years prior to entry

Drugs and Other Treatments to be Excluded

1. 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
2. Any other investigational treatments during study. This includes participation in any medical device or other therapeutic intervention clinical trials.
3. Radiotherapy for target lesions within 4 weeks prior to first study drug administration and during study
4. 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
5. Strong inhibitors and/or inducers of cytochrome P450 (CYP) isoenzyme 3A4 within 2 weeks prior to first study drug administration and during study
6. Immunosuppressive or systemic hormonal therapy within 2 weeks prior to first study drug administration and during study.
7. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; 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; AVID100 is administered once every 3 weeks
Experimental: Phase 2a Triple Negative Breast Cancer; 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; AVID100 is administered once every 3 weeks
Experimental: Phase 2a Head and Neck Carcinoma; Addition of 15 patients with squamous head and neck carcinoma. Patients will have 3+ EGFR over-expression.	Drug: AVID100 IV; AVID100 is administered once every 3 weeks
Experimental: Phase 2a Non-Small Cell Lung Carcinoma; Addition of 15 patients with squamous histology non-small cell lung carcinoma. Patients will have 3+ EGFR over-expression	Drug: AVID100 IV; AVID100 is administered once every 3 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Formation Biologics

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): November 28, 2020
• Study Completion (Actual): January 30, 2021

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (Actual): March 29, 2017

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Breast Diseases; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Breast Neoplasms; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms
• Other Study ID Numbers: AVID100-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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