Bortezomib and Pembrolizumab With or Without Pelareorep for the Treatment of Relapsed or Refractory Multiple Myeloma, AMBUSH Trial

NCT05514990 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 16M-22-1NCI-2022-06505P30CA014089
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial studies the safety of the combination of bortezomib, dexamethasone, and pembrolizumab with or without pelareorep in treating patients with multiple myeloma that has come back (relapsed) or does not response to treatment (refractory). Chemotherapy drugs, such as bortezomib and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. A virus modified in the laboratory, such as pelareorep, may be able to kill cancer cells without damaging normal cells. Giving the combination of bortezomib, dexamethasone, and pembrolizumab with pelareorep may work better in treating patient with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicities (DLTs) (Phase 1B)

  Incidence of dose-limiting toxicities resulting from pelareorep (PELA) in combination with bortezomib-dexamethasone (BOR-D) and pembrolizumab will be assessed. Severity of Adverse Events (AEs) will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  During the 21 days of cycle 1

• Incidence and severity of adverse events (AEs) (Phase 1B)

  Incidence and severity of adverse events (AEs) will be graded according to NCI CTCAE version 5.0, and changes in clinical laboratory parameters.

  Up to 30 days following cessation of study intervention

• Overall response rate (ORR) (complete response [CR] + partial response [PR]) (Phase 2)

  Overall response rate, complete response partial response per the International Myeloma Working Group (IMWG) Uniform Response Criteria for multiple myeloma (MM).

  Up to 3 years

Secondary Outcomes (6)

• ORR (CR + PR) (Phase 1B)

  Up to 3 years

• Duration of response (DOR) (Phase 2)

  Up to 3 years

• Progression-free survival (PFS) (Phase 2)

  Up to 3 years

• Overall survival (OS) (Phase 2)

  Up to 3 years

• Incidence of adverse events (Phase 2)

  From the time of intervention allocation through 90 days following cessation of study intervention or 30 days following cessation of study intervention

Other Outcomes (6)

• Changes in gene expression (Phase 1B, Phase 2)

  Up to 3 years

• Changes in the T cell repertoire within peripheral blood and the TME (Phase 1B, Phase 2)

  Up to 3 years

• Changes in the expression of immune-related biomarkers (Phase 1B, Phase 2)

  Up to 3 years

Study Arms (2)

Cohort I (standard therapy)

EXPERIMENTAL

Patients receive bortezomib SC) or IV and dexamethasone PO, IV, or IM on days 1, 8, and 15 of each cycle. Patients also receive pembrolizumab IV over 30 minutes on day 9 of each cycle. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Drug: Dexamethasone; Biological: Pembrolizumab

Cohort II (standard therapy, pelareorep)

EXPERIMENTAL

Patients receive bortezomib SC or IV and dexamethasone either PO, IV, or IM on days 1, 8, and 15 of each cycle. Patients also receive pelareorep IV over 60 minutes on days 1, 2, 8, 9, 15, and 16 and pembrolizumab IV over 30 minutes on day 9 of each cycle. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Drug: Dexamethasone; Biological: Pelareorep; Biological: Pembrolizumab

Interventions

Bortezomib DRUG

Given SC or IV

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Cohort I (standard therapy); Cohort II (standard therapy, pelareorep)

Dexamethasone DRUG

Given PO, IV, or IM

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Cohort I (standard therapy); Cohort II (standard therapy, pelareorep)

Pelareorep BIOLOGICAL

Given IV

Also known as: PO BB0209, PO-BB0209, Reolysin, Reovirus Serotype 3, Wild-type Reovirus

Cohort II (standard therapy, pelareorep)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Cohort I (standard therapy); Cohort II (standard therapy, pelareorep)

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory multiple myeloma (MM) after at least 3 previous lines of therapy. Previous treatment must have included a proteasome inhibitor (bortezomib, ixazomib or carfilzomib), an immunomodulatory agent (thalidomide, lenalidomide or pomalidomide) and an anti cd38 monoclonal antibody.
• Histologically confirmed diagnosis of MM with measurable disease, as defined by the presence of monoclonal immunoglobulin protein in serum electrophoreses of at least 0.5 g/dL for immunoglobulin G (IgG) or 0.25 g/dL for IgA, or measurable light chain in serum (100 mg/L) or urinary excretion of at least 200 mg monoclonal light chain per 24 hours.
• No continuing acute toxic effects (except alopecia) of any prior chemotherapy, radiotherapy or surgical procedures. All such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 grade =\< 1. Surgery (except minor procedures such as biopsies, intravenous \[IV\]-line placement, etc.) must have occurred at least 28 days prior to study enrollment.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Male or female \>= 18 years of age at the time of signing the informed consent form (ICF).
• Life expectancy of at least 3 months.
• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of relapse, refractory multiple myeloma will be enrolled in this study.
• A male participant must agree to use a contraception during the treatment period and for at least 7 months after the last dose of study treatment and refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 7 months after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial, indicating that the patient is aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, possible alternative therapies, potential benefits, side effects, risks, and discomforts.
• Be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests.
• Absolute neutrophil count (ANC) \>= 1000/uL (collected within 10 days prior to the start of study intervention).
• Platelets \>= 50,000/uL (collected within 10 days prior to the start of study intervention).

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
• Note: Participants must have recovered from all AEs due to previous therapies to =\< grade 1 or baseline. Participants with =\< grade 2 neuropathy may be eligible. Participants with endocrine -related AEs grade =\< 2 requiring treatment or hormone replacement may be eligible.
• Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease. Palliative radiotherapy is allowed while on study treatment for treatment of symptomatic lesions.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus calmette-guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 5 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) or other noninvasive or indolent hat have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients.

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; reolysin; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Kevin R Kelly, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: August 25, 2022
• Study Start: October 7, 2022
• Primary Completion (Estimated): August 22, 2026
• Study Completion (Estimated): August 22, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-11

Locations

US (2)