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

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Some tumors are difficult to treat with chemotherapy or radiation. One of the reasons is that areas of the tumor do not have many blood vessels, which makes it difficult for drugs to reach those areas. One way that researchers have recently tried to overcome this problem is by injecting special kinds of bacteria into the tumors. These bacteria have been genetically changed to remove the chemicals that are poisonous to humans, but are still able to cause tumor cells to break down and die. The idea is that these bacteria may be able to assist chemotherapy drugs in fighting cancer. The goal of this clinical research study is to find the highest tolerable dose of one of these bacterial therapies (Clostridium novyi-NT spores) that can be given in combination with pembrolizumab to patients with advanced solid tumors. The safety of this drug will also be studied, as well as whether it can help to control the disease. This is an investigational study. Clostridium novyi-NT is not FDA approved or commercially available. It is currently being used for research purposes only. Pembrolizumab is FDA approved for the treatment of melanoma and different types of head and neck and non-small cell lung cancers. It is investigational to use these drugs in combination with each other in various types of advanced cancers. The study doctor can describe how the study drugs are designed to work. Up to 18 participants will be enrolled in this study. All will take part at MD Anderson.

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 the combination of Pembrolizumab and Clostridium Novyi-NT generally safe for humans?

Pembrolizumab has been shown to be safe in human clinical trials, with no significant toxic effects observed in nonhuman primate studies. Clostridium Novyi-NT has been used in early clinical studies and animal models, showing potential as a cancer treatment, but more research is needed to fully understand its safety in humans. ^{1 2 3 4 5}

What makes the treatment with Pembrolizumab and Clostridium Novyi-NT unique for cancer?

This treatment is unique because it combines Pembrolizumab, an immune checkpoint inhibitor that enhances the body's immune response against cancer cells, with Clostridium Novyi-NT, a bacterium that can selectively target and destroy tumor cells, offering a novel approach to cancer therapy. ^{2 6 7 8 9}

What data supports the effectiveness of the drug pembrolizumab in treating cancer?

Pembrolizumab, a drug that helps the immune system fight cancer, has shown effectiveness in treating various cancers like non-small cell lung cancer and melanoma by blocking a pathway that tumors use to hide from the immune system. It has also shown promise in treating certain types of lymphoma, although more studies are needed. ^{2 6 10 11 12}

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, 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 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 (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]

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]

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 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]

Citations

1. Singapore pubmed.ncbi.nlm.nih.gov

Clinical outcomes of pembrolizumab therapy in advanced-NSCLC patients with poor performance status (≥3) and high PD-L1 expression (TPS ≥50%): A case series. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

4. United States 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. [2021]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Clostridium novyi-NT in cancer therapy. [2020]

7. China pubmed.ncbi.nlm.nih.gov

Clostridium to treat cancer: dream or reality? [2020]

8. United States pubmed.ncbi.nlm.nih.gov

An intravenous pancreatic cancer therapeutic: Characterization of CRISPR/Cas9n-modified Clostridium novyi-Non Toxic. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Bacteriolytic therapy of experimental pancreatic carcinoma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Previously Treated Advanced or Metastatic Urothelial Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. [2020]

12. New Zealand pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. [2020]