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)

Study Overview

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)

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.

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.

Non Small Cell Lung Cancer
Pancreatic Ductal Adenocarcinoma

DRUG: Mavrostobart (PT199)
DRUG: Tislelizumab
DRUG: Gemcitabine + nab-Paclitaxel
DRUG: Docetaxel
DRUG: Pemetrexed
DRUG: Gemcitabine
DRUG: Carboplatin + Pemetrexed
DRUG: Pembrolizumab + Carboplatin + Pemetrexed

PT199X1101

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	Results Reporting Dates	Study Record Updates
First Submitted 2022-05-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-29
First Submitted that Met QC Criteria 2022-06-21	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-31
First Posted (ACTUAL) 2022-06-24	Results First Posted N/A	Last Verified 2025-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Part A: Monotherapy Dose Escalation 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.	DRUG: Mavrostobart (PT199) Mavrostobart (PT199) is an anti-CD73 mAb with a differentiated mechanism of action.
EXPERIMENTAL: Part B: Combination Therapy Dose Escalation 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.	DRUG: Mavrostobart (PT199) Mavrostobart (PT199) is an anti-CD73 mAb with a differentiated mechanism of action. DRUG: Tislelizumab Anti-PD-1 monoclonal antibody 200 mg Q3W, inhibits the lymphocytes PD-1 receptors, blocking the ligands that would deactivate it and prevent an immune response.
EXPERIMENTAL: Part C: Combination Therapy Dose Expansion 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.	DRUG: Mavrostobart (PT199) Mavrostobart (PT199) is an anti-CD73 mAb with a differentiated mechanism of action. DRUG: Tislelizumab Anti-PD-1 monoclonal antibody 200 mg Q3W, inhibits the lymphocytes PD-1 receptors, blocking the ligands that would deactivate it and prevent an immune response.
EXPERIMENTAL: Part D: Chemotherapy Combination 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,	DRUG: Mavrostobart (PT199) Mavrostobart (PT199) is an anti-CD73 mAb with a differentiated mechanism of action. DRUG: Gemcitabine + nab-Paclitaxel Dosing is per Standard of Care. DRUG: Docetaxel Dosing is per Standard of Care. DRUG: Pemetrexed Dosing is per Standard of Care. DRUG: Gemcitabine Dosing is per Standard of Care. DRUG: Carboplatin + Pemetrexed Dosing is per Standard of Care. DRUG: Pembrolizumab + Carboplatin + Pemetrexed Dosing is per Standard of Care.

Primary Outcome Measures	Measure Description	Time Frame
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	Measure Description	Time Frame
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.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Phanes Therapeutics

Phone Number: 858-766-0852

Email: clinical-trials@phanestx.com

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:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Cohort D1: a histologically or cytologically confirmed diagnosis of pancreatic ductal adenocarcinoma (PDAC), treatment naïve for advanced or metastatic disease, and eligible to receive standard of care treatment with gemcitabine plus nab-paclitaxel.
Cohort D2: a histologically or cytologically confirmed diagnosis of NSCLC without actionable genomic alterations (AGAs) such as EGFR or ALK mutations and radiological documentation of disease progression on prior treatments, which may include a checkpoint inhibitor. Patients have progressed under first-line (1L) SOC chemotherapy with or without ICI or later lines of therapy, or for which standard 1L therapy has proven to be ineffective, intolerable, or is considered inappropriate.
Cohort D3: a histologically or cytologically confirmed diagnosis of NSCLC without actionable genomic alterations (AGAs) such as EGFR or ALK mutations. Patients are treatment naïve and have no contra indication to receive carboplatin plus pemetrexed.
Cohort D4: a histologically or cytologically confirmed diagnosis of NSCLC without actionable genomic alterations (AGAs) such as EGFR or ALK mutations. Patients are treatment naïve and are eligible for 1L therapy with pembrolizumab and carboplatin plus pemetrexed. 3. In all Parts, should be able to provide a tumor tissue sample (archival or newly acquired biopsy) to be assessed for CD73 and other biomarkers (PD-L1), unless deemed by the Investigator to cause risk to the patient or per Investigator's discretion. 4. ECOG performance status of 0 or 1. 5. Adequate organ function confirmed at screening and within 72 hours of initiating treatment.

Collaborators and Investigators

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