Dose Escalation/Expansion Study of Mavrostobart (PT199), an Anti-CD73 MAb, Administered Alone and in Combination with a PD-1 Inhibitor or Chemotherapy (the MORNINGSTAR Study)
- Conditions
- Non Small Cell Lung CancerPancreatic Ductal Adenocarcinoma
- Interventions
- Drug: Mavrostobart (PT199)Drug: Carboplatin + PemetrexedDrug: Pembrolizumab + Carboplatin + Pemetrexed
- Registration Number
- NCT05431270
- Lead Sponsor
- Phanes Therapeutics
- Brief Summary
This is a first-in-human, Phase 1/2, open-label, study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Mavrostobart (PT199) alone and in combination with a PD-1 inhibitor or chemotherapy.
- Detailed Description
Mavrostobart (PT199) is an anti-CD73 mAb with a differentiated mechanism of action and is expected to completely inhibit CD73 enzyme activity. Mavrostobart (PT199) is designed to counter the adenosine-mediated immunosuppressive tumor microenvironment, rendering anti-tumor immune cells to be more active and more responsive to checkpoint immunotherapies, such as PD-1/PD-L1 inhibitors.
CD73 is widely overexpressed in a number of different cancers, including pancreatic ductal adenocarcinoma (PDAC), gastric carcinoma, colorectal carcinoma, non-small cell lung cancer (NSCLC), sarcomas and glioblastomas. Thus, targeting CD73 may provide benefit for patients with a high CD73 expression in their tumor.
Mavrostobart (PT199) addresses the limitations of current CD73 inhibitors and is expected to increase antitumor immune activation, especially in combination with PD-1 pathway inhibition, and thus offer a new treatment option for cancer patients.
NSCLC is known to have a high expression level of CD73, and emerging clinical data has shown that targeting CD73 may provide clinical benefit, when combined with an immune checkpoint inhibitor (ICI) and/or standard of care chemotherapies to overcome treatment resistance.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Monotherapy Dose Escalation Mavrostobart (PT199) A standard 3+3 dose escalation design will be employed, and 3 patients will be enrolled initially at each dose level. Mavrostobart (PT199) will be administered as a monotherapy. Part B: Combination Therapy Dose Escalation Mavrostobart (PT199) A standard 3+3 dose escalation design will be employed, and 3 patients will be enrolled initially at each dose level. Patients will be treated with Mavrostobart (PT199) in combination with a PD-1 inhibitor, tislelizumab. Part B: Combination Therapy Dose Escalation Tislelizumab A standard 3+3 dose escalation design will be employed, and 3 patients will be enrolled initially at each dose level. Patients will be treated with Mavrostobart (PT199) in combination with a PD-1 inhibitor, tislelizumab. Part C: Combination Therapy Dose Expansion Mavrostobart (PT199) Two RDEs for Part C will be determined in Part B and will be further evaluated in two dose expansion cohorts. Patients will be treated with Mavrostobart (PT199) in combination with a PD-1 inhibitor, tislelizumab. Part C: Combination Therapy Dose Expansion Tislelizumab Two RDEs for Part C will be determined in Part B and will be further evaluated in two dose expansion cohorts. Patients will be treated with Mavrostobart (PT199) in combination with a PD-1 inhibitor, tislelizumab. Part D: Chemotherapy Combination Mavrostobart (PT199) The Chemotherapy Combination Therapy Dose Escalation and Expansion will investigate four cohorts, one in frontline PDAC, two in frontline NSCLC and one in second-line and later NSCLC patients. Patients will receive Mavrostobart (PT199) plus chemotherapy, with one cohort also receiving pembrolizumab. Part D: Chemotherapy Combination Gemcitabine + nab-Paclitaxel The Chemotherapy Combination Therapy Dose Escalation and Expansion will investigate four cohorts, one in frontline PDAC, two in frontline NSCLC and one in second-line and later NSCLC patients. Patients will receive Mavrostobart (PT199) plus chemotherapy, with one cohort also receiving pembrolizumab. Part D: Chemotherapy Combination Docetaxel The Chemotherapy Combination Therapy Dose Escalation and Expansion will investigate four cohorts, one in frontline PDAC, two in frontline NSCLC and one in second-line and later NSCLC patients. Patients will receive Mavrostobart (PT199) plus chemotherapy, with one cohort also receiving pembrolizumab. Part D: Chemotherapy Combination Pemetrexed The Chemotherapy Combination Therapy Dose Escalation and Expansion will investigate four cohorts, one in frontline PDAC, two in frontline NSCLC and one in second-line and later NSCLC patients. Patients will receive Mavrostobart (PT199) plus chemotherapy, with one cohort also receiving pembrolizumab. Part D: Chemotherapy Combination Gemcitabine The Chemotherapy Combination Therapy Dose Escalation and Expansion will investigate four cohorts, one in frontline PDAC, two in frontline NSCLC and one in second-line and later NSCLC patients. Patients will receive Mavrostobart (PT199) plus chemotherapy, with one cohort also receiving pembrolizumab. Part D: Chemotherapy Combination Carboplatin + Pemetrexed The Chemotherapy Combination Therapy Dose Escalation and Expansion will investigate four cohorts, one in frontline PDAC, two in frontline NSCLC and one in second-line and later NSCLC patients. Patients will receive Mavrostobart (PT199) plus chemotherapy, with one cohort also receiving pembrolizumab. Part D: Chemotherapy Combination Pembrolizumab + Carboplatin + Pemetrexed The Chemotherapy Combination Therapy Dose Escalation and Expansion will investigate four cohorts, one in frontline PDAC, two in frontline NSCLC and one in second-line and later NSCLC patients. Patients will receive Mavrostobart (PT199) plus chemotherapy, with one cohort also receiving pembrolizumab.
- Primary Outcome Measures
Name Time Method To determine the maximum tolerated dose (MTD), if reached. Start of the study drug till 90 days after last dose. Recommended Phase 2 Dose of Mavrostobart (PT199) as a single agent and/or in combination with a PD-1 inhibitor. Start of the study drug till 90 days after last dose. Dose Limiting Toxicity (DLT). Time Frame: Start of the study drug till 90 days after last dose.
- Secondary Outcome Measures
Name Time Method Preliminary efficacy assessed by the response rate by RECIST 1.1 for overall response rate. Start of the study drug till 90 days after last dose. Area Under the Curve from time 0 to last (AUC0-last) of Mavrostobart (PT199) Time Frame: Start of the study drug till 90 days after last dose. Maximum Concentration (Cmax) of Mavrostobart (PT199) Time Frame: Start of the study drug till 90 days after last dose. Half Life (T1/2) of Mavrostobart (PT199) Time Frame: Start of the study drug till 90 days after last dose. Preliminary efficacy assessed by the response rate by RECIST 1.1 for disease control rate. Time Frame: Start of the study drug till 90 days after last dose. Progression free survival duration. Time Frame: Start of the study drug till 90 days after last dose. 6-month overall survival. Time Frame: Start of the study drug till 90 days after last dose.
Trial Locations
- Locations (6)
Carolina BioOncology Institute
🇺🇸Huntersville, North Carolina, United States
Sarah Cannon Research Institute University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Tranquility Research
🇺🇸Webster, Texas, United States
NEXT Oncology
🇺🇸Fairfax, Virginia, United States