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)

NCT05431270 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PT199X1101
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

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.

Conditions

Non Small Cell Lung Cancer; Pancreatic Ductal Adenocarcinoma

Keywords

Advanced; Metastatic; Refractory; Anti-CD73; Checkpoint immunotherapies; PD-1/PD-L1 inhibitors

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• 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.

Study Arms (4)

Part A: Monotherapy Dose Escalation

EXPERIMENTAL

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)

Part B: Combination Therapy Dose Escalation

EXPERIMENTAL

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); Drug: Tislelizumab

Part C: Combination Therapy Dose Expansion

EXPERIMENTAL

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); Drug: Tislelizumab

Part D: Chemotherapy Combination

EXPERIMENTAL

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.

Drug: Mavrostobart (PT199); Drug: Gemcitabine + nab-Paclitaxel; Drug: Docetaxel; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Carboplatin + Pemetrexed; Drug: Pembrolizumab + Carboplatin + Pemetrexed

Interventions

Mavrostobart (PT199) DRUG

Mavrostobart (PT199) is an anti-CD73 mAb with a differentiated mechanism of action.

Part A: Monotherapy Dose Escalation; Part B: Combination Therapy Dose Escalation; Part C: Combination Therapy Dose Expansion; Part D: Chemotherapy Combination

Tislelizumab DRUG

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.

Part B: Combination Therapy Dose Escalation; Part C: Combination Therapy Dose Expansion

Gemcitabine + nab-Paclitaxel DRUG

Dosing is per Standard of Care.

Also known as: abraxane

Part D: Chemotherapy Combination

Docetaxel DRUG

Dosing is per Standard of Care.

Part D: Chemotherapy Combination

Pemetrexed DRUG

Dosing is per Standard of Care.

Part D: Chemotherapy Combination

Gemcitabine DRUG

Dosing is per Standard of Care.

Part D: Chemotherapy Combination

Carboplatin + Pemetrexed DRUG

Dosing is per Standard of Care.

Part D: Chemotherapy Combination

Pembrolizumab + Carboplatin + Pemetrexed DRUG

Dosing is per Standard of Care.

Part D: Chemotherapy Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors.
• For Part A: a histologically or cytologically confirmed unresectable advanced or metastatic solid tumors previously treated with therapies, or for which treatment is not available or not tolerated.
• For Part B: 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, or patients diagnosed with metastatic and/or advanced (m/a) PDAC who have disease progression after previously treated with therapies, or for which treatment is not available or not tolerated.
• For Part C: A histologically or cytologically confirmed diagnosis of NSCLC without actionable genomic alterations such as EGFR or ALK mutations and radiological documentation of disease progression on prior treatments, which may include a checkpoint inhibitor.
• For Part D:
• 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.
• 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.
• ECOG performance status of 0 or 1.
• Adequate organ function confirmed at screening and within 72 hours of initiating treatment.

You may not qualify if:

• Women who are pregnant or lactating.
• Women of child-bearing potential (WOCBP) who do not use adequate birth control.
• Autoimmune disease requiring systemic treatment within the past twelve months. Active autoimmune disease or a history of autoimmune diseases that may relapse.
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to study treatment.
• Patients who have experienced Grade ≥ 3 immune-related events, such as (non-infectious) pneumonitis, interstitial lung disease, myocarditis.
• Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed.
• Impaired cardiac function or significant diseases.
• Patients who have ≥ Grade 3 neuropathy.
• Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy.
• Patients who are currently receiving (last dose within 5 days from C1D1) treatment with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants.

Sponsors & Collaborators

• Phanes Therapeutics: lead
• BeiGene: collaborator

Study Sites (6)

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

RECRUITING

Sarah Cannon Research Institute University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Tranquility Research

Webster, Texas, 77598, United States

RECRUITING

NEXT Oncology

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

tislelizumab; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Docetaxel; Pemetrexed; Carboplatin; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Coordination Complexes

Central Study Contacts

Phanes Therapeutics

CONTACT

858-766-0852; clinical-trials@phanestx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will consist of 4 parts: Monotherapy Dose Escalation (Part A), ICI Combination Therapy Dose Escalation (Part B), ICI Combination Dose Expansion in NSCLC (Part C), and Combination with Chemotherapy in frontline (1L) PDAC patients (Part D).

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: June 24, 2022
• Study Start: August 11, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: January 31, 2025

Record last verified: 2025-01

Locations

US (6)