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
Overview
- Phase
- Phase 1
- Intervention
- DM919
- Conditions
- Advanced Solid Tumor
- Sponsor
- D2M Biotherapeutics Inc.
- Enrollment
- 160
- Locations
- 2
- Primary Endpoint
- RDEs or RP2Ds of DM919 alone and in combination with pembrolizumab
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provide a signed written informed consent form (ICF) before any study-specific assessment.
- •Be at least 18 years old on the day of signing the ICF.
- •Have a histologically confirmed advanced metastatic or unresectable, locally invasive solid cancer.
- •For monotherapy dose escalation cohorts from the 3mg/kg dose level, preferred indications include endometrial cancer, cervical cancer, non-small cell lung cancer, hepatocellular cancer, oral cavity cancer (parotid, salivary gland and others), HPV (+) laryngeal cancer and bile duct cancer. Other indications can be included as both sponsor and investigators agree.
- •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.
- •Have at least one measurable tumor lesion per RECIST 1.
- •Have a life expectancy of ≥3 months.
- •Have an ECOG performance status of 0 or
- •Have adequate organ and bone marrow function.
- •Female subjects must meet either of the following criteria:
Exclusion Criteria
- •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.
- •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.
- •Any history of discontinuation from prior therapy with anti-PD-1 or anti-PD-L1 inhibitor due to drug-related toxicity.
- •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.
- •Radiotherapy within 2 weeks before the first dose of study treatment.
- •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.
- •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.
- •Any history of severe hypersensitivity to monoclonal antibodies or another form of severe hypersensitivity.
- •Grade ≥3 viral, bacterial, or fungal infection within 2 weeks before the first dose of study treatment.
- •Known active HIV infection, as determined by detectable HIV-RNA viral load.
Arms & Interventions
Module A Dose Escalation
Patients with advanced solid tumors enrolled in dose escalation cohorts treated with DM919
Intervention: DM919
Module A Cohort Expansion
Patients with select solid tumor types enrolled in expansion cohorts treated with DM919 at a dose selected from the Module A Escalation arm
Intervention: DM919
Module B Combination Therapy Dose Escalation
Patients with advanced solid tumors enrolled in dose escalation cohorts treated with DM919 in combination with pembrolizumab
Intervention: DM919
Module B Combination Therapy Dose Escalation
Patients with advanced solid tumors enrolled in dose escalation cohorts treated with DM919 in combination with pembrolizumab
Intervention: Pembrolizumab
Module B Combination Therapy Cohort Expansion
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
Intervention: DM919
Module B Combination Therapy Cohort Expansion
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
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
RDEs or RP2Ds of DM919 alone and in combination with pembrolizumab
Time Frame: Up to 24months
The tentative RDE(s) and RP2D(s) will be identified from the totality of the safety, PK / PDx, and preliminary anti-tumor efficacy data.
Number of treatment-emergent events (TEAEs) in Dose Escalation
Time Frame: Up to 24 months
TEAE is defined as adverse events reported for the first time or worsening of a pre-existing event after the first dose of study drug.
Secondary Outcomes
- All cohorts(Up to 24 months)