ACTIVE_NOT_RECRUITING

A Study of DM919 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A First-in-Human Open-label, Phase 1a / 1b Dose Escalation and Expansion Cohort Study of DM919, a Novel Anti-MICA/B Antibody, as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

Quick Facts

Study Start:2024-04-09

Study Completion:2026-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06328673

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Provide a signed written informed consent form (ICF) before any study-specific assessment. 2. Be at least 18 years old on the day of signing the ICF. 3. Have a histologically confirmed advanced metastatic or unresectable, locally invasive solid cancer. 4. Have experienced progressive disease on at least one approved SOC systemic anti-cancer therapy for a given tumor type, or have been intolerant to SOC therapy, or in the opinion of the Investigator, have been considered ineligible for SOC therapy on medical grounds, or have no proven curative or life-prolonging approved SOC therapies available. 5. Have at least one measurable tumor lesion per RECIST 1.1. 6. Have a life expectancy of ≥3 months. 7. Have an ECOG performance status of 0 or 1. 8. Have adequate organ and bone marrow function. 9. Female subjects must meet either of the following criteria: 1. Women of childbearing potential (WOCBP, defined as \<12 continuous months of amenorrhea with no identified cause other than menopause, or not surgically sterile) 2. Postmenopausal or surgically sterile females. 10. Male subjects with female partners of childbearing potential must agree to remain sexually abstinent or use condoms during the treatment period and for at least 120 days after the last dose of study treatments. 11. Male subjects must agree to not donate or preserve sperm during the treatment period and for at least 120 days after the last dose of study treatments. 12. Able and willing to comply with the protocol and the restrictions and assessments therein.	1. Received prior systemic anticancer treatment within 3 weeks before the first dose of study treatment (or 5 half-lives, whichever is shorter) or within 4 weeks before the first dose of study treatment in case of nitrosoureas or radio-immuno conjugate therapy. 2. Current evidence of Grade ≥2 toxicity of prior therapy, except for any grade alopecia, Grade ≤2 peripheral neuropathy, and the following Grade ≤2 vitiligo, Grade ≤2 psoriasis not requiring systemic treatment and immune related Grade ≤2 endocrine disorders adequately managed by hormonal replacement therapy. 3. Any history of discontinuation from prior therapy with anti-PD-1 or anti-PD-L1 inhibitor due to drug-related toxicity. 4. Major surgery within 7 days before the first dose of study treatment or planned after the start of treatment, where 'major' is defined as any surgical procedure that requires more than 24 hours admission in a hospital. 5. Radiotherapy within 2 weeks before the first dose of study treatment. 6. Current evidence of symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Symptomatic treated brain metastases are allowed if subjects are clinically stable in the judgement of the investigator. 7. Other primary malignancy histologically different than the cancer under study, that has required active treatment within 2 years before the first dose of study treatment or may require active treatment during the treatment period. 8. Any history of severe hypersensitivity to monoclonal antibodies or another form of severe hypersensitivity. 9. Grade ≥3 viral, bacterial, or fungal infection within 2 weeks before the first dose of study treatment. 10. Known active HIV infection, as determined by detectable HIV-RNA viral load. 11. Known active HBV infection, as determined by detectable HBV-DNA viral load. 12. Known active HCV infection, as determined by detectable HCV-RNA viral load. 13. Known active or latent tuberculosis (TB). Testing for TB is not required at screening. 14. Known active SARS-CoV-2 (COVID-19) infection, as determined by a positive COVID-19 test result within 2 weeks before the first dose of study treatment. 15. Received a live or live-attenuated vaccine within 4 weeks before the first dose of study treatment. Injectable influenza vaccine and COVID-19 vaccine are permitted 16. Uncontrolled or significant cardiovascular disease. 17. Autoimmune disease that has required systemic treatment (i.e., disease modifying agents, corticosteroids above physiological doses \[\>10 mg daily of prednisone or equivalent\] or immunosuppressive drugs) within 2 years before the first dose of study treatment. 18. Any history of interstitial lung disease (ILD, including pneumonitis) that required systemic corticosteroid therapy. 19. Diagnosis of immunodeficiency or receiving chronic systemic corticosteroid therapy at doses \>10 mg daily of prednisone or equivalent or any other form of immunosuppressive therapy within 14 days before the first dose of study treatment. 20. Had an allogeneic solid organ or stem cell transplant. 21. Received systemic corticosteroid use at doses \>10 mg daily of prednisone or equivalent within 2 weeks before the first dose of study treatment or other systemic immunosuppressive agents within 4 weeks before the first dose of study treatment. 22. Received hematopoietic growth factors (G-SCF, GM-CSF, EPO) or transfusion of blood components (RBC or platelets) within 2 weeks before the first dose of study treatment, or likely to require treatment with these agents during Cycle 1. 23. Pregnant or breastfeeding women. 24. History or clinical evidence of any surgical or medical condition that the Investigator judges as likely to interfere with the results of the study or pose an additional risk to study subjects, such as rapidly progressive or uncontrolled disease involving a major organ system (e.g., disorders of vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an immunodeficiency, or clinically significant active psychiatric or abuse disorders). 25. History of chronic substance abuse within 12 months of the start of treatment. 26. Sensitive substrates of cytochrome P450 enzymes should be excluded within 2 weeks (or 5 half-lives of the agent, whichever is longer) before the start of dosing in Phase 1a Dose Escalation part of the study.

Inclusion Criteria

Exclusion Criteria

1. Provide a signed written informed consent form (ICF) before any study-specific assessment.
2. Be at least 18 years old on the day of signing the ICF.
3. Have a histologically confirmed advanced metastatic or unresectable, locally invasive solid cancer.
4. Have experienced progressive disease on at least one approved SOC systemic anti-cancer therapy for a given tumor type, or have been intolerant to SOC therapy, or in the opinion of the Investigator, have been considered ineligible for SOC therapy on medical grounds, or have no proven curative or life-prolonging approved SOC therapies available.
5. Have at least one measurable tumor lesion per RECIST 1.1.
6. Have a life expectancy of ≥3 months.
7. Have an ECOG performance status of 0 or 1.
8. Have adequate organ and bone marrow function.
9. Female subjects must meet either of the following criteria:
1. Women of childbearing potential (WOCBP, defined as \<12 continuous months of amenorrhea with no identified cause other than menopause, or not surgically sterile)
2. Postmenopausal or surgically sterile females.
10. Male subjects with female partners of childbearing potential must agree to remain sexually abstinent or use condoms during the treatment period and for at least 120 days after the last dose of study treatments.
11. Male subjects must agree to not donate or preserve sperm during the treatment period and for at least 120 days after the last dose of study treatments.
12. Able and willing to comply with the protocol and the restrictions and assessments therein.

1. Received prior systemic anticancer treatment within 3 weeks before the first dose of study treatment (or 5 half-lives, whichever is shorter) or within 4 weeks before the first dose of study treatment in case of nitrosoureas or radio-immuno conjugate therapy.
2. Current evidence of Grade ≥2 toxicity of prior therapy, except for any grade alopecia, Grade ≤2 peripheral neuropathy, and the following Grade ≤2 vitiligo, Grade ≤2 psoriasis not requiring systemic treatment and immune related Grade ≤2 endocrine disorders adequately managed by hormonal replacement therapy.
3. Any history of discontinuation from prior therapy with anti-PD-1 or anti-PD-L1 inhibitor due to drug-related toxicity.
4. Major surgery within 7 days before the first dose of study treatment or planned after the start of treatment, where 'major' is defined as any surgical procedure that requires more than 24 hours admission in a hospital.
5. Radiotherapy within 2 weeks before the first dose of study treatment.
6. Current evidence of symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Symptomatic treated brain metastases are allowed if subjects are clinically stable in the judgement of the investigator.
7. Other primary malignancy histologically different than the cancer under study, that has required active treatment within 2 years before the first dose of study treatment or may require active treatment during the treatment period.
8. Any history of severe hypersensitivity to monoclonal antibodies or another form of severe hypersensitivity.
9. Grade ≥3 viral, bacterial, or fungal infection within 2 weeks before the first dose of study treatment.
10. Known active HIV infection, as determined by detectable HIV-RNA viral load.
11. Known active HBV infection, as determined by detectable HBV-DNA viral load.
12. Known active HCV infection, as determined by detectable HCV-RNA viral load.
13. Known active or latent tuberculosis (TB). Testing for TB is not required at screening.
14. Known active SARS-CoV-2 (COVID-19) infection, as determined by a positive COVID-19 test result within 2 weeks before the first dose of study treatment.
15. Received a live or live-attenuated vaccine within 4 weeks before the first dose of study treatment. Injectable influenza vaccine and COVID-19 vaccine are permitted
16. Uncontrolled or significant cardiovascular disease.
17. Autoimmune disease that has required systemic treatment (i.e., disease modifying agents, corticosteroids above physiological doses \[\>10 mg daily of prednisone or equivalent\] or immunosuppressive drugs) within 2 years before the first dose of study treatment.
18. Any history of interstitial lung disease (ILD, including pneumonitis) that required systemic corticosteroid therapy.
19. Diagnosis of immunodeficiency or receiving chronic systemic corticosteroid therapy at doses \>10 mg daily of prednisone or equivalent or any other form of immunosuppressive therapy within 14 days before the first dose of study treatment.
20. Had an allogeneic solid organ or stem cell transplant.
21. Received systemic corticosteroid use at doses \>10 mg daily of prednisone or equivalent within 2 weeks before the first dose of study treatment or other systemic immunosuppressive agents within 4 weeks before the first dose of study treatment.
22. Received hematopoietic growth factors (G-SCF, GM-CSF, EPO) or transfusion of blood components (RBC or platelets) within 2 weeks before the first dose of study treatment, or likely to require treatment with these agents during Cycle 1.
23. Pregnant or breastfeeding women.
24. History or clinical evidence of any surgical or medical condition that the Investigator judges as likely to interfere with the results of the study or pose an additional risk to study subjects, such as rapidly progressive or uncontrolled disease involving a major organ system (e.g., disorders of vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an immunodeficiency, or clinically significant active psychiatric or abuse disorders).
25. History of chronic substance abuse within 12 months of the start of treatment.
26. Sensitive substrates of cytochrome P450 enzymes should be excluded within 2 weeks (or 5 half-lives of the agent, whichever is longer) before the start of dosing in Phase 1a Dose Escalation part of the study.

Contacts and Locations

Principal Investigator

Shiraj Sen, MD

PRINCIPAL_INVESTIGATOR

NEXT Oncology

Ning Li

PRINCIPAL_INVESTIGATOR

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

Study Locations (Sites)

NEXT Oncology

San Antonio, Texas, 78216

United States

Collaborators and Investigators

Sponsor: D2M Biotherapeutics Inc.

Shiraj Sen, MD, PRINCIPAL_INVESTIGATOR, NEXT Oncology
Ning Li, PRINCIPAL_INVESTIGATOR, The Cancer Institute and Hospital, Chinese Academy of Medical Sciences(CAMS)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-04-09

Study Completion Date2026-03-01

Study Record Updates

Study Start Date2024-04-09

Study Completion Date2026-03-01

Terms related to this study

Additional Relevant MeSH Terms

Advanced Solid Tumor