Evaluating Mavrostobart for advanced lung and pancreatic cancer

A Phase 1, Open-Label, Dose Escalation and Expansion Study of Mavrostobart (PT199) Administered Alone in Adult Patients with Advanced Solid TuMORs, in CombiNation with a Checkpoint INhibitor TreatinG Wild-type Non-Small Cell Lung Cancer, or in Combination with ChemoTherapy for Metastatic or Advanced PAncreatic Ductal AdenocaRcinoma (MORNINGSTAR)

This study is testing a new treatment called Mavrostobart to see if it can help people with advanced lung and pancreatic cancer by boosting their immune response against tumors.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Phanes Therapeutics (Industry-sponsored)
• Drugs / interventions: pembrolizumab, chemotherapy, radiation
• Locations: 6 sites (Huntersville, North Carolina and 5 other locations)
• Trial ID: NCT05431270 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and effectiveness of Mavrostobart (PT199), an anti-CD73 monoclonal antibody, both alone and in combination with a PD-1 inhibitor or chemotherapy. It aims to inhibit CD73 enzyme activity to enhance immune response against tumors, particularly in patients with non-small cell lung cancer and pancreatic ductal adenocarcinoma. The study is structured in phases to assess pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with advanced or metastatic solid tumors. Participants will be monitored for their response to treatment and any adverse effects.

Who should consider this trial

Good fit: Ideal candidates include patients with unresectable advanced or metastatic non-small cell lung cancer or pancreatic ductal adenocarcinoma who have previously received treatment.

Not a fit: Patients with actionable genomic alterations such as EGFR or ALK mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced cancers that are currently difficult to treat.

How similar studies have performed: Other studies targeting CD73 have shown promise, suggesting that this approach may be beneficial, although this specific combination is novel.

Eligibility criteria

Key Inclusion Criteria

1. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors.
2. 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.
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.

Key Exclusion Criteria

1. Women who are pregnant or lactating.
2. Women of child-bearing potential (WOCBP) who do not use adequate birth control.
3. Autoimmune disease requiring systemic treatment within the past twelve months. Active autoimmune disease or a history of autoimmune diseases that may relapse.
4. Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to study treatment.
5. Patients who have experienced Grade ≥ 3 immune-related events, such as (non-infectious) pneumonitis, interstitial lung disease, myocarditis.
6. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed.
7. Impaired cardiac function or significant diseases.
8. Patients who have ≥ Grade 3 neuropathy.
9. 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.
10. 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.

Additional inclusion and exclusion criteria will apply.

Where this trial is running

Huntersville, North Carolina and 5 other locations

• Carolina BioOncology Institute — Huntersville, North Carolina, United States (Recruiting)
• Sarah Cannon Research Institute University of Oklahoma — Oklahoma City, Oklahoma, United States (Recruiting)
• SCRI Oncology Partners — Nashville, Tennessee, United States (Recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Tranquility Research — Webster, Texas, United States (Recruiting)
• NEXT Oncology — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Phanes Therapeutics

Conditions Non Small Cell Lung Cancer; Pancreatic Ductal Adenocarcinoma; Advanced; Metastatic; Refractory; Anti-CD73; Checkpoint immunotherapies; PD-1/PD-L1 inhibitors