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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called DM919, both alone and with pembrolizumab (also known as KEYTRUDA), to determine a safe and effective dose for people with solid tumors. It aims to identify which cancer types respond well to these treatments. Participants will receive the treatment through an intravenous infusion, and researchers will monitor tumor reactions. This trial may suit individuals with advanced solid tumors whose disease has progressed after standard treatments or who cannot undergo such treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

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

Research shows that pembrolizumab is usually well-tolerated by patients with various solid tumors. Previous studies have linked it to long-lasting effects in controlling cancer growth. Common side effects include tiredness and mild skin reactions, which most patients manage well.

DM919 is a new treatment with limited information available. This trial marks one of the first instances of testing it in humans, with the primary goal of determining a safe dose. As testing is in its early stages, understanding its safety remains a priority.

When combined with pembrolizumab, researchers are carefully monitoring the safety of DM919. The trial aims to assess tolerance and identify the optimal dose for future studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DM919 in combination with pembrolizumab because it offers a potentially novel approach for treating advanced solid tumors. Unlike many treatments that primarily focus on one mechanism, DM919 may have a unique action that, when combined with pembrolizumab—a well-known immunotherapy drug—could enhance the immune system's ability to recognize and attack cancer cells. This combination aims to boost treatment effectiveness, potentially leading to better outcomes for patients who may not respond well to existing therapies.

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

Studies have shown that DM919, when used alone, can shrink tumors in various types of cancer. It becomes more effective when combined with other treatments. In this trial, some participants will receive DM919 alone, while others will receive it with pembrolizumab. Another study found that pembrolizumab effectively treats many solid tumors and extends patient survival. When combined with pembrolizumab, DM919 significantly improves survival rates for cancer patients. This suggests that DM919, particularly when paired with pembrolizumab, could effectively treat certain cancers. ^{1 2 3 5 6}

Who Is on the 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)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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, 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) 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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06328673

NCT06328673 | A Study of DM919 Alone and in ... 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 ...

2. synapse.patsnap.com synapse.patsnap.com/blog/micab-antibody-dm919-enters-phase-1-trial-for-advanced-solid-tumors-by-d2m-biotherapeutics

MICA/B Antibody DM919 Enters Phase 1 Trial for ... In preclinical trials, DM919 exhibited notable antitumor properties as a singular therapeutic agent across various tumor models. When combined ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/d2m-solid-tumour-trial/

D2M Biotherapeutics doses first subject in solid tumour trial DM919 has shown antitumor activity as a monotherapy in a variety of tumour models and synergistic anti-tumour effects when combined with anti- ...

4. trialstat.com trialstat.com/2024/04/d2m-biotherapeutics-announces-first-patient-dosed-in-a-phase-1-study-evaluating-dm919-a-novel-mica-b-antibody-for-treating-patients-with-advanced-solid-tumors/

D2M Biotherapeutics Announces First Patient Dosed in A Phase ... D2M Biotherapeutics Announces First Patient Dosed in A Phase 1 Study Evaluating DM919, a Novel MICA/B Antibody for Treating Patients with Advanced Solid Tumors.

5. withpower.com withpower.com/trial/phase-1-neoplasms-2-2024-d99fb

DM919 + Pembrolizumab for Cancer The updated analysis showed a favorable overall survival (OS) hazard ratio of 0.56 for the pembrolizumab plus PC group, indicating a significant survival ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT06328673

A Study of DM919 Alone and in Combination ... This phase 1, first-in-human, multicenter, dose-escalation and expansion trial (NCT06328673) will evaluate the safety, tolerability, pharmacokinetics, ...