A Study of OPD5 Followed by Autologous Stem Cell Transplant for Patients With Relapsed Refractory Multiple Myeloma (COAST)

An Open-label Phase I, Dose Escalation Study of the Safety and Tolerability of OPD5 as Myeloablative Conditioning Regimen Followed by Autologous Stem Cell Transplant (ASCT) for Patients With Relapsed Refractory Multiple Myeloma (RRMM)

The purpose of this study is to evaluate the safety and tolerability of a single infusion of OPD5 before Autologous Stem Cell Transplant in patients with RRMM. The study will evaluate increasing doses of OPD5 to find the best dose and to assess any side effects. Each patient will be assigned to a dose cohort of 3-6 patients to receive one single dose of OPD5. Each patient will be hospitalized for about 14 days from the OPD5 infusion and then have monthly visits to the clinic for 3 months and then every third month until disease progression or starting new myeloma treatment, maximum up to 2 years.

Study Overview

• Status: Withdrawn
• Conditions: Multiple Myeloma; Relapse Multiple Myeloma
• Intervention / Treatment: Drug: OPD5

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 62500
    • University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
  • Ostrava, Czechia
    • University Hospital Ostrava, Clinic of Hematooncology
  • Praha, Czechia
    • Charles University and General Hospital in Prague, 1st Department of Medicine - Department of Hematology, First Faculty of Medicine

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, between the ages of 18 years and 70 years at the planned time of study treatment; patients greater than 70 years of age may qualify on a case by case basis
• Diagnosis of multiple myeloma
• Received a previous Autologous Stem Cell Transplantation ( ASCT) (single or tandem) that resulted in disease progression within 24 months
• Received at least 2 prior lines of therapy
• Refractory to previous treatment with a Proteasome Inhibitor (PI), an immunomodulatory drug (IMiD) and an anti-Cluster of Differentiation 38 monoclonal antibody (anti-CD38 mAb)
• Male and women of childbearing potential agrees to use contraception during the treatment period and during a specified time period after the last dose

Exclusion Criteria:

• Prior treatment with melphalan flufenamide (melflufen) or OPD5
• Any medical condition that may interfere with safety or participation in this study
• Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance
• Prior allogeneic stem cell transplantation or prior salvage ASCT

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

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose cohort 1; In dose cohort 1, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level of 30 mg/m2 (dose based on body surface area)	Drug: OPD5; OPD5 solution for i.v. infusion
Experimental: Dose cohort 2; In dose cohort 2, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 1	Drug: OPD5; OPD5 solution for i.v. infusion
Experimental: Dose cohort 3; In dose cohort 3, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 2	Drug: OPD5; OPD5 solution for i.v. infusion
Experimental: Dose cohort 4; In dose cohort 4, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 3	Drug: OPD5; OPD5 solution for i.v. infusion
Experimental: Dose cohort 5; In dose cohort 5, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 4	Drug: OPD5; OPD5 solution for i.v. infusion
Experimental: Dose cohort 6; In dose cohort 6, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 5	Drug: OPD5; OPD5 solution for i.v. infusion
Experimental: Dose cohort 7; In dose cohort 7, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 6	Drug: OPD5; OPD5 solution for i.v. infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and grade of Treatment Emergent Adverse Events (TEAEs)	Including frequency and grade of defined Dose Limiting Toxicities	30 days post OPD5 treatment with ASCT
Incidence of clinically significant changes in clinical laboratory parameters		30 days post OPD5 treatment with ASCT
Magnitude of clinically significant changes in clinical laboratory parameters		30 days post OPD5 treatment with ASCT
Incidence of clinically significant adverse findings in vital signs		30 days post OPD5 treatment with ASCT
Severity of clinically significant adverse findings in vital signs		30 days post OPD5 treatment with ASCT
Incidence of clinically significant adverse findings in electrocardiograms (ECGs)		30 days post OPD5 treatment with ASCT
Severity of clinically significant adverse findings in electrocardiograms (ECGs)		30 days post OPD5 treatment with ASCT
Incidence of clinically significant adverse findings in other physical examination parameters		30 days post OPD5 treatment with ASCT
Severity of clinically significant adverse findings in other physical examination parameters		30 days post OPD5 treatment with ASCT
Incidence of mucositis		30 days post OPD5 treatment with ASCT
Severity of mucositis	Using World Health Organization (WHO) oral toxicity scale, from 0 (no change) to 4 (oral feeding is not possible)	30 days post OPD5 treatment with ASCT
The number of deaths not related to relapse or progression		100 days post OPD5 treatment with ASCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response	Best response for a single patient. Best response will include the following categories: stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) and Progressive Disease (PD) as assessed by the investigator according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC)	30 days post OPD5 treatment with ASCT
Overall Response Rate (ORR)	Proportion of patients who achieve response of CR, sCR, VGPR or PR as their best response.	approximately 100 days post OPD5 treatment with ASCT
Duration of response (DOR)	Time from the first confirmed response of sCR, CR, VGPR or PR to first confirmed disease progression, or death due to any cause	approximately 12 months
Time to progression (TTP)	Time from the date of OPD5 administration to the date of the first documented confirmed PD	approximately 12 months
Time to next treatment (TTNT)	Time from the date of OPD5 administration start to the start of first post study myeloma therapy (maintenance MM treatment not considered as new line of therapy)	approximately 12 months
Progression Free Survival (PFS)	Time from the date of OPD5 dosing to the date of first documentation of confirmed progressive disease (PD) or death due to any cause	approximately 12 months
Pharmacokinetics Area under the curve AUC(0-t) for OPD5 and the metabolites desethyl-melflufen and melphalan		Day -1 (the day of OPD5 infusion)
Pharmacokinetics AUC(0-infinity) for OPD5 and the metabolites desethyl-melflufen and melphalan		Day -1 (the day of OPD5 infusion)
Pharmacokinetics elimination half-life (t½) for OPD5 and the metabolites desethyl-melflufen and melphalan		Day -1 (the day of OPD5 infusion)
Pharmacokinetics Cmax for OPD5 and the metabolites desethyl-melflufen and melphalan		Day -1 (the day of OPD5 infusion)
Time to hematological recovery	defined as the return of Absolute Neutrophil Count (ANC) ≥ 0.5 x 10^9/L and platelets ≥ 20 x 10^9/L for two consecutive days	approximately Day 14
Time to myeloablation	defined as the first of at least two consecutive days with ANC < 0.5 x 10^9/L and platelets <20 x 10^9/L	approximately Day 14
Minimal Residual Disease (MRD) status by Next Generation sequencing (NGS) in patients that achieve a CR or VGPR.		approximately Day 100

Collaborators and Investigators

• Sponsor: Oncopeptides AB
• Investigators: Principal Investigator: Sergio Giralt, MD, Memorial Sloan Kettering Cancer Centre, New York City, United States

Study record dates

Study Major Dates

• Study Start (Anticipated): May 27, 2021
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: June 4, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): November 26, 2021
• Last Update Submitted That Met QC Criteria: November 17, 2021
• Last Verified: November 1, 2021

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: OP-501

Drug and device information, study documents

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