DPX-Survivac and Pembrolizumab With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

NCT04920617 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: P1605-SUR-D23KEYNOTE-C54
• Study Type: interventional
• Target: 102
• Locations: 10 countries
• Sites: 50

Brief Summary

This is a Phase 2b, randomized, open label study to assess the safety and efficacy of DPX-Survivac and pembrolizumab, with and without low-dose cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL.

Conditions

Relapsed Diffuse Large B-cell Lymphoma; Refractory Diffuse Large B-cell Lymphoma

Keywords

Immunotherapy; T cell activation; DLBCL; Anti-PD-1; CAR-T ineligible; ASCT ineligible

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) in each of the study arms

  Centrally evaluated using Lugano (2014)

  Approximately 24 months

Secondary Outcomes (8)

• Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms

  Approximately 24 months

• Duration of response (DOR) in each of the study arms

  Approximately 24 months

• Time to response in each of the study arms

  Approximately 24 months

• Progression-Free Survival in each of the study arms

  Approximately 48 months

• Disease control rate (DCR) in each of the study arms

  Approximately 24 months

Other Outcomes (6)

• Objective Response Rate (ORR) based on PD-L1 expression

  Approximately 24 months

• Time to next treatment (TTNT) in each of the study arms

  Approximately 48 months

• Overall survival (OS) in each of the study arms

  Approximately 48 months

Study Arms (2)

Arm 1: DPX-Survivac, pembrolizumab, CPA

EXPERIMENTAL

Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. CPA will be self-administered 50 mg BID for 7 days on and 7 days off starting on D0.

Drug: DPX-Survivac; Drug: Pembrolizumab; Drug: CPA

Arm 2: DPX-Survivac, pembrolizumab

EXPERIMENTAL

Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. Subjects randomized to Arm 2 will not receive CPA.

Drug: DPX-Survivac; Drug: Pembrolizumab

Interventions

DPX-Survivac DRUG

SC injection on D7 and D28, then every 8 weeks

Also known as: maveropepimut-S

Arm 1: DPX-Survivac, pembrolizumab, CPA; Arm 2: DPX-Survivac, pembrolizumab

Pembrolizumab DRUG

IV infusion every 3 weeks

Also known as: MK-3475, Keytruda

Arm 1: DPX-Survivac, pembrolizumab, CPA; Arm 2: DPX-Survivac, pembrolizumab

CPA DRUG

50 mg twice daily, week on then week off

Also known as: Intermittent, low-dose cyclophosphamide, Procytox, Cytoxan

Arm 1: DPX-Survivac, pembrolizumab, CPA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years of age who are willing and able to provide written informed consent
• Have an ECOG performance status of ≤ 1. Subjects with an ECOG performance status of 2 may be enrolled with Medical Monitor approval.
• Pathologically confirmed diagnosis of DLBCL, as defined by the 2016 World Health Organization classification including DLBCL NOS high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, Epstein-barr virus (EBV) positive DLBCL, and T cell rich B cell lymphoma (TCRBCL). Subjects with DLBCL transformed from indolent lymphoma (except for Richter's transformation) are eligible.
• Subjects must have progressive disease following at least two (2) lines of prior systemic therapy for DLBCL; prior treatment must have included an anthracycline and rituximab (or another CD20-targeted agent).
• Subjects must have failed or be ineligible for ASCT or CAR-T
• Have at least one bi-dimensionally measurable lesion per Lugano (2014)
• Willing to provide pre-treatment and on-treatment tumor biopsy tissue.
• Meet protocol-specified laboratory requirements
• Life expectancy \> 3 months.

You may not qualify if:

• Primary CNS lymphoma or active secondary CNS involvement and/or lymphomatous meningitis
• Chemotherapy, immunotherapy, major surgery, or investigational agent treatment within 28 days of D0 or 5 half-lives, whichever is shorter
• Radiotherapy within 14 days of day 0
• Autologous stem cell transplant (ASCT) within ˂100 days prior to D0
• Chimeric antigen receptor T cell (CAR-T) therapy within ˂28 days prior to D0
• Diagnosis of immunodeficiency disorder or history of active autoimmune disease that has required systemic treatment in the past 2 years
• Uncontrolled significant active infections (controlled Hepatitis B, Hepatitis C, or HIV may be eligible)
• Prior history of malignancy other than eligible lymphoma sub-types, unless the subject has been free of the disease for ≥ 2 years prior to the start of study treatment

Sponsors & Collaborators

• ImmunoVaccine Technologies, Inc. (IMV Inc.): lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (50)

Compassionate Cancer Care Medical Group

Fountain Valley, California, 92708, United States

RECRUITING

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

WITHDRAWN

BRCR Medical Center Inc.

Hollywood, Florida, 33021, United States

WITHDRAWN

BRCR Medical Center Inc.

Plantation, Florida, 33322, United States

WITHDRAWN

Comprehensive Hematology and Oncology

St. Petersburg, Florida, 33709, United States

WITHDRAWN

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

RECRUITING

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

Tulane Cancer Center Office of Clinical Research

New Orleans, Louisiana, 70112, United States

RECRUITING

Oncology Hematology West, PC dba Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Christus St. Vincent Regional Cancer Center

Santa Fe, New Mexico, 87505, United States

RECRUITING

Brody School of Medicine at East Carolina University

Greenville, North Carolina, 27834, United States

RECRUITING

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

WITHDRAWN

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

WITHDRAWN

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

RECRUITING

Allegheny Health Network (AHN) West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Reading Hospital - McGlinn Cancer Institute

West Reading, Pennsylvania, 19611, United States

RECRUITING

Prairie Lakes Health Care System

Watertown, South Dakota, 57201, United States

WITHDRAWN

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Epworth Freemasons Hospital

Melbourne, Victoria, 3002, Australia

RECRUITING

Box Hill Hospital

Melbourne, Victoria, 3128, Australia

RECRUITING

Westmead Hospital

Westmead, 2145, Australia

RECRUITING

Saskatoon Cancer Center

Saskatoon, Saskatchewan, S7H 4H4, Canada

RECRUITING

Hôpital Avicenne

Bobigny, 93000, France

RECRUITING

Centre d'Oncologie de Gentilly

Nancy, 54000, France

RECRUITING

Hôpital Privé du Confluent

Nantes, 44277, France

RECRUITING

Centre Antoine Lacassagne

Nice, 06189, France

RECRUITING

Hôpital Saint-Antoine

Paris, 75012, France

RECRUITING

Hôpital de la Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

Hôpital Necker

Paris, 75015, France

RECRUITING

CHU Bordeaux- Hôpital Haut Lévêque

Pessac, 33600, France

RECRUITING

Centre Hospitalier de Périgueux

Périgueux, 24019, France

RECRUITING

Centre Hospitalier de Saint-Quentin

Saint-Quentin, 02321, France

RECRUITING

Debreceni Egyetem Klinikai Központ

Debrecen, 4032, Hungary

RECRUITING

SzSzBM Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, 4400, Hungary

RECRUITING

North Shore Hospital

Auckland, Auckland Province, 0622, New Zealand

RECRUITING

Palmerston North Hospital

Palmerston North, Manawatu, 4414, New Zealand

RECRUITING

Szpitale Pomorskie Sp. z o. o.

Gdynia, 85-519, Poland

RECRUITING

Wojewódzki Szpital Specjalistyczny w Legnicy

Legnica, 59-220, Poland

RECRUITING

SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, 10-228, Poland

RECRUITING

Centrum Medyczne Pratia Poznań

Skórzewo, 60-185, Poland

RECRUITING

Narodowy Instytut Onkologii im. Marii, Skłodowskiej-Curie

Warsaw, 02-781, Poland

RECRUITING

Bucharest Oncology Institute "Prof.Dr.Al. Trestioreanu"

Bucharest, 022328, Romania

RECRUITING

The Oncology Institute "Prof. Dr. Ion Chiricuţă" I.O.C.H.

Cluj-Napoca, 400015, Romania

RECRUITING

University Clinical Center of Serbia

Belgrade, 11000, Serbia

RECRUITING

Oncology Institute of Vojvodina

Kamenitz, 21204, Serbia

RECRUITING

University Clinical Center Kragujevac

Kragujevac, 34000, Serbia

RECRUITING

Clinical Hospital Center Zemun

Zemun, 11080, Serbia

RECRUITING

Hospital Santa Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

Hospital Universitario de Burgos

Burgos, 09006, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

pembrolizumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 10, 2021
• Study Start: June 18, 2021
• Primary Completion: October 1, 2024
• Study Completion: April 1, 2025
• Last Updated: April 7, 2023

Record last verified: 2022-08

Locations

CA (1); NZ (2); FR (10); US (17); AU (4); HU (2); PL (5); ES (3); RO (2); SE (4)