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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Multiple Myeloma, Multiple Myeloma in Relapse, Multiple Myeloma With Failed Remission

Intervention / Treatment
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* Drug: FOR46


Participation Criteria
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Eligibility Criteria
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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).

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: Sequential Assignment
Interventional Model Description: Following completion of the dose escalation phase of the study and determination of a recommended phase 2 dose, patients will be enrolled into a dose expansion cohort.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: FOR46 (Dose Escalation)<br>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<br>* FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46<br>|
| Experimental: Experimental: FOR46 (Dose Expansion)<br>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<br>* FOR46 is an intravenously (IV) administered antibody-drug conjugate (ADC) directed against CD46<br>|

What is the study measuring?
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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 |