A Study of FOR46 in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)

A Phase I Study of FOR46 Administered Every 21 Days in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)

This study will test the safety and efficacy of FOR46 given every 21 days to patients with relapsed or refractory multiple myeloma.

The name of the study drug involved in this study is: FOR46 for Injection

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Multiple Myeloma in Relapse; Multiple Myeloma With Failed Remission
• Intervention / Treatment: Drug: FOR46

Detailed Description

This study is designed to evaluate the safety, tolerability and antitumor activity of FOR46 in patients with relapsed or refractory multiple myeloma. This study will be conducted in two parts:

Dose escalation:

This part will evaluate increasing doses of FOR46 to identify the maximum tolerated dose (MTD). The first patient enrolled on the study will receive the lowest dose of FOR46. Once this dose is shown to be safe, a second patient will be enrolled at the next higher dose. Patients will continue to be enrolled into either single or multiple patient groups receiving increasing doses until the MTD is reached.

Dose expansion:

This part of the study will further evaluate the safety, tolerability and antitumor activity of FOR46 at a dose shown to be safe in the dose escalation part of the study.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63310
      • Washington University in St. Louis-Siteman Cancer Center
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mt. Sinai

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:

• Male or female ≥ 18 years of age
• Measurable MM that is relapsed or refractory to established therapies with known clinical benefit in RRMM or intolerant of those established MM therapies. Prior lines of therapy must include a proteasome inhibitor (PI), an immunomodulatory imide drug (IMiD) and a CD38-directed therapy in any order of combination.
• ECOG performance status of 0 or 1
• Adequate hematologic, renal and hepatic function
• Females of child-bearing potential must have a negative serum pregnancy test and use a medically acceptable form of contraception
• Male patients with with female partners of childbearing potential must agree to use 2 effective methods of contraception
• Patients must provide signed informed consent

Exclusion Criteria:

• Persistent clinically significant toxicities from previous anticancer therapy
• NCI CTCAE Grade ≥ 2 peripheral neuropathy from any etiology or has a genetic disorder that is associated with peripheral neuropathy even without current neuropathic manifestations
• Has received treatment with a stem cell transplant within 12 weeks before administration of patient's first dose of FOR46
• Has had radiation or systemic anticancer therapy within 14 days before first dose of FOR46
• Has received treatment with an investigational drug within 28 days before first dose of FOR46
• Has had a major surgical procedure within 28 days before administration of the patient's first FOR46 dose
• Is breastfeeding
• Clinically significant cardiovascular disease
• Uncontrolled, clinically significant pulmonary disease
• Uncontrolled intercurrent illness
• Has known positive status for HIV or either active/chronic hepatitis B/C
• Requires anticoagulation with warfarin or direct thrombin inhibitor; a washout of 7 days before the administration of a patient's first FOR46 dose is required for patients removed from these treatments
• Requires medications that are strong inhibitors or strong inducers of CYP3A4
• Has a history of episodic atrial fibrillation or flutter; patients with chronic atrial fibrillation are not excluded.
• Prior treatment with an ADC containing Monomethyl auristatin E (MMAE) or Monomethyl auristatin F (MMAF).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: FOR46 (Dose Escalation); Eligible patients will receive FOR46 administered as an IV infusion every 21 days. Patients will be enrolled into escalating dose levels during the Dose Escalation period of the study.	Drug: FOR46; FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46
Experimental: Experimental: FOR46 (Dose Expansion); Eligible patients will receive FOR46 administered as an IV infusion every 21 days. Patients will receive the maximum tolerated dose during the Dose Expansion period of the study.	Drug: FOR46; FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Number of patients with treatment-related adverse events as assessed by NCI CTCAE v5.0.	Through 1 month following last dose
Occurrence of dose-limiting toxicities	The severity and incidence of dose-limiting toxicities related to escalating dose levels of FOR46	Through 1 month following last dose
Disease response	Overall response rate of FOR46, defined as all responses greater than or equal to a partial response, complete response, stringent complete response, or minimal residual disease negativity	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize FOR46 plasma concentration	FOR46 maximum plasma concentration	Through 1 month following last dose
Characterize the FOR46 area under the curve	FOR46 area under the plasma concentration-time curve	Through 1 month following last dose
Characterize FOR46 elimination	FOR46 elimination half-life	Through 1 month following last dose
Antidrug Antibodies	Change from baseline in serum levels of antidrug antibodies	Through 1 month following last dose
Duration of response	Assessed by IMWG criteria	From first dose through 6 months following last dose
Progression-free survival	Assessed by IMWG criteria	From first dose through 6 months following last dose
Time to progression	Assessed by IMWG criteria	From first dose through 6 months following last dose

Collaborators and Investigators

• Sponsor: Fortis Therapeutics, Inc.
• Investigators: Study Director: Andrew Dorr, MD, Fortis Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2019
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: August 21, 2018
• First Submitted That Met QC Criteria: August 26, 2018
• First Posted (Actual): August 28, 2018

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: FOR46-002

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