AVID100 in Advanced Epithelial Carcinomas

• ClinicalTrials.gov Identifier: NCT03094169
• Recruitment Status: Terminated
• First Posted: March 29, 2017
• Last Update Posted: March 24, 2021
• Sponsor: Formation Biologics
• Information provided by (Responsible Party): Formation Biologics

Tracking Information

• First Submitted Date: February 6, 2017
• First Posted Date: March 29, 2017
• Last Update Posted Date: March 24, 2021
• Actual Study Start Date: February 1, 2017
• Actual Primary Completion Date: November 28, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 28, 2019)

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

Original Primary Outcome Measures (submitted: March 22, 2017)

Determine safety and tolerability of AVID100 [ Time Frame: 6 months ]

Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Current Secondary Outcome Measures (submitted: August 28, 2019)

PK Profile of Total Antibody [ Time Frame: 18 months ]

Characterization of the pharmacokinetic profile of total antibody

Original Secondary Outcome Measures (submitted: March 22, 2017)

• PK Profile of Total Antibody [ Time Frame: 9 months ]
  Characterization of the pharmacokinetic profile of total antibody (AVID100 plus mAb100)
• Evaluation of the preliminary anti-neoplastic effects of AVID100 [ Time Frame: 9 months ]
  Number of Participants with evidence of objective response or stable disease and duration of response

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: AVID100 in Advanced Epithelial Carcinomas
• Official Title: 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
• Brief Summary: 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

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
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment

Condition

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

Intervention

Drug: AVID100 IV

AVID100 is administered once every 3 weeks

Study Arms

• 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.
  Intervention: Drug: AVID100 IV
• 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.
  Intervention: Drug: AVID100 IV
• Experimental: Phase 2a Head and Neck Carcinoma
  Addition of 15 patients with squamous head and neck carcinoma. Patients will have 3+ EGFR over-expression.
  Intervention: Drug: AVID100 IV
• 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
  Intervention: Drug: AVID100 IV

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 22, 2021): 49
• Original Estimated Enrollment (submitted: March 22, 2017): 30
• Actual Study Completion Date: January 30, 2021
• Actual Primary Completion Date: November 28, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03094169
• Other Study ID Numbers: AVID100-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Formation Biologics
• Original Responsible Party: Same as current
• Current Study Sponsor: Formation Biologics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Nehal Lakhani, MD; START Midwest

• PRS Account: Formation Biologics
• Verification Date: March 2021