DM919 + Pembrolizumab for Cancer

Recruiting at 1 trial location

Overseen By Jing Yang

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: D2M Biotherapeutics Inc.

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: HIV, HBV, HCV, TB, others

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

Compensation: Varies

Number of Visits: 18

Duration: 24 weeks

160 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to define a safe and effective dose of DM919 for participants with solid tumors The main questions it aims to answer are: What is the safe and effective dose of DM919 when used alone or in combination with pembrolizumab? What cancers can be treated effectively with DM919 alone or in combination with pembrolizumab?? Participants will be asked to attend clinic and be given a intravenous infusion of DM919 or DM-919 in combination with pembrolizumab. They will have blood tests and other assessments to measure whether DM-919 will have the effect on tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have received certain cancer treatments or medications affecting the immune system shortly before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug DM919 + Pembrolizumab for cancer?

Pembrolizumab, a part of the treatment, has shown effectiveness in treating various cancers, including non-small cell lung cancer and melanoma, by helping the immune system attack cancer cells. It has been approved for use in several types of cancer, indicating its potential benefit in combination with other treatments like DM919. ^{1 2 3 4 5}

What safety information is available for pembrolizumab (Keytruda) in cancer treatment?

Pembrolizumab (Keytruda) has been associated with some side effects, including fatigue, cough, nausea, skin rash, and diarrhea. More serious immune-related side effects can occur, such as lung inflammation (pneumonitis), inflammation of the colon (colitis), liver inflammation (hepatitis), and thyroid problems. Rarely, it can cause type 1 diabetes. ^{3 4 6 7 8}

What makes the drug DM919 + Pembrolizumab unique for cancer treatment?

The combination of DM919 with Pembrolizumab is unique because Pembrolizumab is a PD-1 inhibitor that helps the immune system attack cancer cells by blocking a pathway that tumors use to hide from immune cells. This combination may offer a novel approach by potentially enhancing the immune response against cancer compared to using Pembrolizumab alone. ^{2 3 4 9 10}

Research Team

Shiraj Sen, MD, PhD

Principal Investigator

NEXT Oncology

Ning Li

Principal Investigator

The Cancer Institute and Hospital, Chinese Academy of Medical Sciences(CAMS)

Eligibility Criteria

This trial is for individuals with advanced solid tumors. Participants must be able to attend clinic visits, receive intravenous infusions, and undergo blood tests and other assessments.

Inclusion Criteria

Able and willing to comply with the protocol and the restrictions and assessments therein

Have a life expectancy of ≥3 months

Provide a signed written informed consent form (ICF) before any study-specific assessment

Exclusion Criteria

I do not have any major health issues that could affect the study.

I have not had radiotherapy in the last 2 weeks.

I have another type of cancer that was treated within the last 2 years or might need treatment soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusions of DM919 alone or in combination with pembrolizumab, with blood tests and assessments to measure effects on tumors

24 weeks

Every 6 weeks for the first 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 12 weeks until disease progression

Treatment Details

Interventions

• DM919
• Pembrolizumab

Trial Overview The study is testing the safety and effectiveness of a drug called DM919 alone, and in combination with another drug named Pembrolizumab. It aims to find the right dose that's both safe and effective against certain cancers.

Participant Groups

Group I: Module B Combination Therapy Dose Escalation Experimental Treatment 2 Interventions

Patients with advanced solid tumors enrolled in dose escalation cohorts treated with DM919 in combination with pembrolizumab

Group II: Module B Combination Therapy Cohort Expansion Experimental Treatment 2 Interventions

Patients with select tumor types enrolled in expansion cohorts treated with DM919 at a dose selected from the Module B Escalation arm, in combination with pembrolizumab

Group III: Module A Dose Escalation Experimental Treatment 1 Intervention

Patients with advanced solid tumors enrolled in dose escalation cohorts treated with DM919

Group IV: Module A Cohort Expansion Experimental Treatment 1 Intervention

Patients with select solid tumor types enrolled in expansion cohorts treated with DM919 at a dose selected from the Module A Escalation arm

DM919 is already approved in China, United States for the following indications:

Approved in China as DM919 for:

• Advanced solid tumors

Approved in United States as DM919 for:

• Advanced solid tumors

Who Is Running the Clinical Trial?

D2M Biotherapeutics Inc.

Lead Sponsor

Trials

1

Recruited

160+

Findings from Research

In a study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab and pemetrexed-carboplatin (PC) significantly improved the objective response rate (56.7% vs. 30.2% with PC alone) and progression-free survival (PFS) compared to PC alone, with a hazard ratio (HR) of 0.53.

The updated analysis showed a favorable overall survival (OS) hazard ratio of 0.56 for the pembrolizumab plus PC group, indicating a significant survival benefit, although 41% of patients experienced grade 3 to 5 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. Borghaei, H., Langer, CJ., Gadgeel, S., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[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, 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]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

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, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

Pembrolizumab is an effective treatment for advanced gastric cancer (AGC) in patients who have already undergone two courses of chemotherapy, showing durable responses and an acceptable safety profile.

Approved by the FDA in 2017 for patients with PD-L1 positive AGC, pembrolizumab is now being studied in combination with other treatments, indicating its potential for broader applications in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pembrolizumab in recurrent or advanced gastric cancer expressing PD-L1 refractory to platinum and fluoropyrimidine. Mishima, S., Kawazoe, A., Shitara, K.[2022]

References

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

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. [2022]

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [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. England pubmed.ncbi.nlm.nih.gov

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

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

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

Safety of pembrolizumab in recurrent or advanced gastric cancer expressing PD-L1 refractory to platinum and fluoropyrimidine. [2022]