What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as bortezomib, dexamethasone, and pembrolizumab, often result in side effects including fatigue, gastrointestinal issues (diarrhea, constipation), peripheral neuropathy, and increased risk of infections. Bortezomib can cause neuropathy and thrombocytopenia, while dexamethasone may lead to hyperglycemia and mood changes. Pembrolizumab, an immunotherapy, can cause immune-related adverse events like pneumonitis and colitis. Lenalidomide and carfilzomib, other common agents, are associated with hematologic toxicities, fatigue, and increased risk of thromboembolic events.

What prior FDA approvals exist?

The FDA has approved several treatments for Multiple Myeloma, including combinations of chemotherapy drugs, immunotherapy, and targeted therapies. Bortezomib, a proteasome inhibitor, and dexamethasone, a corticosteroid, are commonly used in various combinations. Immunotherapy agents like pembrolizumab, a monoclonal antibody, have also been approved. Additionally, daratumumab, another monoclonal antibody targeting CD38, has shown efficacy in combination with other drugs like bortezomib and dexamethasone. While oncolytic virus therapy like Pelareorep is still under investigation, these existing treatments provide a robust framework for managing Multiple Myeloma.

What other types of research exist?

Promising novel alternatives to Pelareorep for Multiple Myeloma patients include the combination of bortezomib, dexamethasone, and pembrolizumab. This combination leverages chemotherapy and immunotherapy to target cancer cells and enhance the immune system's ability to fight the disease. Additionally, enfortumab vedotin-ejfv (Padcev) has received accelerated approval and may offer another innovative treatment option.

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Proteasome Inhibitor

Bortezomib + Pembrolizumab +/- Pelareorep for Multiple Myeloma

Phase 1 & 2

Recruiting

Led By Kevin R Kelly, MD

Research Sponsored by University of Southern California

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically confirmed diagnosis of MM with measurable disease

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Must not have

Clinically significant cardiac disease

History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of chemotherapy drugs, an immunotherapy drug, and a modified virus to treat patients with difficult-to-treat multiple myeloma. The goal is to see if this combination is safe and effective in killing cancer cells and helping the immune system fight the cancer.

Who is the study for?

Adults over 18 with relapsed or refractory multiple myeloma, who've had at least three prior treatments, can join this trial. They should be in good physical condition (ECOG 0-1), have normal thyroid and adrenal hormone levels, and a life expectancy of more than 3 months. People with HIV, active autoimmune diseases requiring recent treatment, certain infections or vaccinations, severe allergies to study drugs' ingredients, CNS metastases, another progressing cancer within the last five years or significant heart issues cannot participate.

What is being tested?

The AMBUSH trial is testing how safe and effective it is to combine bortezomib and dexamethasone (chemotherapy) with pembrolizumab (an immunotherapy antibody) either with or without pelareorep (a modified virus). The goal is to see if these combinations are better for treating patients whose multiple myeloma has returned after previous treatments or isn't responding anymore.

What are the potential side effects?

Possible side effects include reactions related to the immune system attacking normal organs due to pembrolizumab; nerve damage from bortezomib; infection risks from pelareorep; fatigue; hormonal imbalances; blood disorders from chemotherapy agents like dexamethasone; as well as general inflammation throughout the body.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My multiple myeloma is confirmed and measurable.

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I am fully active or can carry out light work.

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My multiple myeloma has returned or didn't respond after 3 treatments.

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I don't have ongoing side effects from past cancer treatments.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious heart condition.

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I have or had lung inflammation that needed steroids.

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I have an active tuberculosis infection.

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I had radiotherapy less than 2 weeks before starting the study treatment.

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I have an autoimmune disease treated with medication in the last 2 years.

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I have dementia or changes in my mental status.

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I have an immune system disorder or I'm on long-term steroids.

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I have another cancer that has gotten worse or needed treatment in the last 5 years.

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I have active brain metastases or carcinomatous meningitis.

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I am currently on medication for an infection.

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I experience significant numbness or pain in my hands or feet.

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I have received an organ or tissue transplant from another person.

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I have had a stem cell transplant from a donor.

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I have been diagnosed with HIV.

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I have received treatment with specific medications before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

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

Heart rate

Secondary study objectives

Duration of response (DOR) (Phase 2)

Incidence of adverse events (Phase 2)

ORR (CR + PR) (Phase 1B)

+3 more

Other study objectives

CD4 and CD8 T-cell reactivity (Phase 1B, Phase 2)

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

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

+3 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort II (standard therapy, pelareorep)Experimental Treatment4 Interventions

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.

Group II: Cohort I (standard therapy)Experimental Treatment3 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bortezomib

2005

Completed Phase 3

~1410

Dexamethasone

2007

Completed Phase 4

~2650

Pelareorep

2010

Completed Phase 2

~160

Pembrolizumab

2017

Completed Phase 3

~3130

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Multiple Myeloma treatments often involve a combination of drugs that target cancer cells through different mechanisms. Bortezomib is a proteasome inhibitor that disrupts protein degradation, leading to cancer cell death. Dexamethasone is a corticosteroid that reduces inflammation and can induce cancer cell apoptosis. Pembrolizumab is an immunotherapy drug that blocks the PD-1 pathway, enhancing the immune system's ability to attack cancer cells. Pelareorep, an oncolytic virus, selectively infects and kills cancer cells while stimulating an anti-tumor immune response. These mechanisms are crucial for Multiple Myeloma patients as they provide a multi-faceted approach to targeting and eliminating cancer cells, potentially improving treatment efficacy and patient outcomes.