Pembrolizumab + Clostridium Novyi-NT for Cancer

Overseen By Rabia Khan

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Immunosuppressants, Antibiotics

Disqualifiers: Brain metastases, Autoimmune disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose of a new bacterial therapy, Clostridium novyi-NT, combined with pembrolizumab (an immunotherapy drug), for treating advanced solid tumors that are difficult to reach with traditional treatments like chemotherapy. Researchers aim to assess whether this combination can effectively combat cancer by breaking down tumor cells and enhancing the efficacy of other drugs. The trial seeks participants with advanced solid tumors that have not responded to previous treatments and can receive injections of the bacterial spores. Participants must also remain close to an emergency room and have a caregiver for 28 days after treatment. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic corticosteroids or other immunosuppressive medications. You also cannot have had chemotherapy, radiation, or biological cancer therapy within four weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using pembrolizumab with Clostridium novyi-NT is generally safe. In one study, the main issue was a serious side effect involving an abscess, a swollen, pus-filled area. This indicates that while some risks exist, the treatment was mostly well-tolerated. Pembrolizumab alone has already received FDA approval for several cancers, offering some reassurance about its safety. However, the safety of combining these two treatments remains under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Clostridium Novyi-NT for cancer because it offers a unique approach compared to traditional treatments like chemotherapy and radiation. Unlike conventional therapies, which often target cancer cells directly, this treatment uses a bacterium, Clostridium Novyi-NT, to infect and break down tumor cells from within. Pembrolizumab, an immunotherapy drug, helps boost the body's immune response to target and destroy cancer cells more effectively. This dual approach not only targets tumors more precisely but also has the potential to reduce side effects associated with broader treatments.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that combining pembrolizumab with Clostridium novyi-NT, the focus of this trial, may help treat certain cancers. In one study, three patients experienced tumor shrinkage, and one patient's tumor disappeared completely. Additionally, 69% of patients maintained stable disease, meaning their cancer did not worsen. The treatment's side effects were manageable, offering encouragement for patients. Clostridium novyi-NT breaks down tumor cells, potentially enhancing pembrolizumab's cancer-fighting ability. Pembrolizumab, already approved for some cancers, blocks a protein that prevents the immune system from attacking cancer cells, making it a strong partner in this combination. ^{1 2 6 7 8}

Who Is on the Research Team?

Sarina Piha-Paul, MD

Principal Investigator

M.D. Anderson Cancer Center

Sarina Piha-Paul, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who've had at least one systemic cancer therapy, can stay near an ER for 28 days post-treatment, have a caregiver, and meet specific health criteria. Pregnant women or those planning pregnancy are excluded.

Inclusion Criteria

I've had at least one cancer treatment when cure wasn't an option.

My advanced cancer can be seen or felt, or identified with imaging.

My cancer has a visible tumor larger than 1 cm but smaller than 12 cm.

Exclusion Criteria

Your oxygen levels are lower than 95% when breathing without extra oxygen.

I need to take medication that weakens my immune system.

I had an organ transplant less than 3 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab by vein every 3 weeks for up to 12 months and a single intratumoral injection of Clostridium novyi-NT on Day 8

12 months

In-person visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 3 months for up to 12 months

12 months

In-person visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Clostridium Novyi-NT
• Pembrolizumab

Trial Overview Researchers are testing the highest dose of Clostridium novyi-NT bacteria that's safe with pembrolizumab in patients with advanced tumors. They want to see if this combo helps control the disease better than current treatments.

How Is the Trial Designed?

Group I: Pembrolizumab + Clostridium novyi-NT Experimental Treatment 3 Interventions

Participants receive Pembrolizumab by vein over about 30 minutes on Day 0 and then every 3 weeks for up to 12 months. Clostridium novyi-NT injected into the tumor on Day 8. Starting on Day 15, participant takes Doxycycline by mouth 2 times a day for the rest of participant's life to lower the risk of further growth of Clostridium novyi-NT

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

BioMed Valley Discoveries, Inc

Industry Sponsor

Trials

19

Recruited

650+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab is a monoclonal antibody that blocks the PD-1/PD-L1 interaction, which is crucial for preventing the immune system from attacking tumors, making it a key player in cancer immunotherapy.

It has been approved by the FDA for treating patients with advanced melanoma who have not responded to previous treatments, highlighting its efficacy in managing difficult cases of this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. Improta, G., Leone, I., Donia, M., et al.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a study of 59 patients with relapsed/refractory extranodal natural killer/T-cell lymphoma treated with pembrolizumab, the overall response rate was 40.7%, with 28.8% achieving a complete response, indicating its potential efficacy as a salvage therapy.

While pembrolizumab showed modest effectiveness, it was associated with some grade 3 or 4 adverse events in 20.3% of patients, with neutropenia being the most common, suggesting that while it can be beneficial, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. Lee, JY., Kwon, JH., Hur, JY., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12434394/

Phase Ib Study of Pembrolizumab in Combination with ... In this study, we present the safety and efficacy results of an open-label, single-center phase Ib study combining pembrolizumab with intratumoral C. novyi-NT ...

2. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/pembrolizumab-cnv-nt-combo-study-results-in-solid-tumors/

Pembrolizumab & CNV-NT Combo Study Results in Solid ... Three partial responses and one complete response were observed; stable disease occurred in 69% of patients. Safety was largely manageable, with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03435952

NCT03435952 | Pembrolizumab With Intratumoral Injection ... This is an investigational study. Clostridium novyi-NT is not FDA approved or commercially available. It is currently being used for research purposes only.

4. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT107/725488/Abstract-CT107-Phase-Ib-Study-of-Pembrolizumab-in

Abstract CT107: Phase Ib Study of Pembrolizumab in ... This phase 1b dose escalation study assessed safety and potential synergistic effects of pembrolizumab and C. novyi-NT in advanced solid tumors.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40643985/

Phase Ib Study of Pembrolizumab in Combination with ... This study highlights the potential of the C. novyi-NT and pembrolizumab combination as a promising therapeutic strategy for ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/18/3864/764537/Phase-Ib-Study-of-Pembrolizumab-in-Combination

Phase Ib Study of Pembrolizumab in Combination with ... In this study, we present the safety and efficacy results of an open-label, single-center phase Ib study combining pembrolizumab with intratumoral C. novyi-NT ...

7. biomed-valley.com biomed-valley.com/news_releases/biomed-valley-discoveries-announces-publication-of-results-from-phase-1b-study-of-pembrolizumab-in-combination-with-clostridium-novyi-nt-cnv-nt-bvd-550-in-patients-with-advanced-solid-tumors-in-clin/

News & Events Led by researchers at MD Anderson Cancer Center, the study demonstrated an overall objective response rate of 25% (n=4) among patients with ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01924689

Safety Study of Intratumoral Injection of Clostridium Novyi- ... This investigational study will measure anti-tumor activity of C. novyi-NT administered intratumoral in patients with treatment-refractory solid tumor ...