RMT in Combination With Durvalumab + Chemo in Untreated Adenocarcinoma NSCLC. A Randomized Double Blind Phase II Trial

NCT04105270 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2019LS010
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 10

Brief Summary

This is a randomized, active-controlled, parallel-group, double-blind Phase II trial, of oral restorative microbiota therapy (RMT) or placebo combined with intravenous (IV) durvalumab (MEDI4736) plus chemotherapy in patients with treatment naïve advanced or metastatic adenocarcinoma non-small cell lung cancer (NSCLC)

Conditions

Adenocarcinoma of Lung; Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Number of patients experiencing Progression Free Survival (PFS)

  Incidence of PFS using RECIST 1.1 in each treatment arm to evaluate the efficacy of restorative microbiota therapy

  3 Years

• Safety and tolerability of RMT

  Safety and tolerability of RMT in combination with durvalumab or durvalumab + chemotherapy as assessed by the incidence of adverse events

  2 Years

Secondary Outcomes (7)

• Objective Response Rate (ORR) RECIST 1.1

  2 Years

• Duration of Response (DOR)

  2 Years

• Overall Survival (OS)

  3 Years

• Immune mediated Adverse Events imAE

  2 Years

• Objective Response Rate (ORR) (iRECIST)

  2 Years

Study Arms (3)

Arm A (RMT)

EXPERIMENTAL

Drug: Oral Restorative Microbiota Therapy (RMT) Capsules; Drug: Durvalumab 1500 mg IV; Drug: Cisplatin/pemetrexed or Carboplatin/pemetrexed

Arm B (Placebo)

EXPERIMENTAL

Drug: Durvalumab 1500 mg IV; Drug: Cisplatin/pemetrexed or Carboplatin/pemetrexed; Other: Placebo

Safety Run-in

EXPERIMENTAL

10 patients are enrolled in this safety run-in arm. Patients are directly assigned to RMT treatment arm. After safety- run-in period of 4 weeks after the first dose of RMT, in the 10 patients if no new safety signal are seen enrollment moves to randomization

Drug: Oral Restorative Microbiota Therapy (RMT) Capsules; Drug: Durvalumab 1500 mg IV; Drug: Cisplatin/pemetrexed or Carboplatin/pemetrexed

Interventions

Oral Restorative Microbiota Therapy (RMT) Capsules DRUG

Patients with PD-L1 TC expression will receive sixteen doses of oral RMT capsules weekly

Also known as: RMT

Arm A (RMT); Safety Run-in

Durvalumab 1500 mg IV DRUG

Patients with PD-L1 TC expression receive durvalumab 1500 mg IV every 4 weeks (Q4W) until disease progression or for a maximum of two years from the 1st dose of durvalumab

Arm A (RMT); Arm B (Placebo); Safety Run-in

Cisplatin/pemetrexed or Carboplatin/pemetrexed DRUG

Patients with PD-L1 TC receive cisplatin/pemetrexed or carboplatin/pemetrexed given every 3 weeks (Q3W) for 4 cycles followed by pemetrexed maintenance given Q3W

Arm A (RMT); Arm B (Placebo); Safety Run-in

Placebo OTHER

Sixteen doses of oral placebo capsules given weekly

Arm B (Placebo)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the lung that is unresectable stage IIIB/C or stage IV, does not have an EGFR sensitizing (activating) mutation or ALK or ROS1 translocation. BRAF, RET, NTRK, MET ex 14 splice site mutation
• Measurable disease based on RECIST 1.1
• Tumor sample requirements
• Mandatory provision of an unstained, archived tumor tissue sample in a quantity sufficient to allow for biomarker and genomic analysis. A minimum of 10 unstained slides should be available for evaluation.
• Known PD-L1 TC expression status assayed by Ventana SP263. Patients who have known PDL-1 as assayed by PharmDx 22C3 assay may be eligible; however, available archival tissue will be used to assay with Ventana SP263 test.
• Prior chemotherapy or immunotherapy as adjuvant therapy for lung cancer is permitted as long as it has been \>6 months from last dose at the time of enrollment. Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable (e.g. by local surgery or radiotherapy). Prior systemic therapy for advanced/metastatic NSCLC makes the patient ineligible for this study.
• Patients with treated brain metastasis are eligible as long as they have stable symptoms, are more than 2 weeks from completion of therapy, and do not require more than 10mg of daily prednisone or equivalent.
• ECOG Performance status of 0 or 1
• Body weight of \>30 kg
• Adequate organ function within 14 days of study enrollment defined as:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤1.5x upper limit of normal (ULN) - this will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT) and ALT (SGPT) ≤2.5 x institutional ULN unless liver metastases are present, in which case it must be ≤5x ULN

You may not qualify if:

• Not pregnant or breast feeding. Evidence of post-menopausal status, or negative urine or serum pregnancy test for female pre-menopausal patients. Women will be considered postmenopausal if they have amenorrhea for 12 months without an alternative medical explanation
• Dysphagia or inability to swallow medications
• Squamous cell, large cell, or NSCLC NOS (not otherwise specified) histology or mixed tumors
• Has untreated brain metastasis or active leptomeningeal carcinomatosis
• Has a known sensitivity to any component of therapeutic agents used in this study
• Receipt of any immunotherapy or investigational drug within 4 weeks prior to the first dose of study drug; and in the case of monoclonal antibodies 6 weeks prior to the first dose of study drug
• Prior treatment with any other anti-PD-1, or PD-L1, including durvalumab or an anti-PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors except as adjuvant therapy for NSCLC so long as it has been greater than six months since the last treatment
• Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug
• Active or prior documented autoimmune disease within the past 2 years requiring systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Active documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) who require immunosuppression or patients who exceed 10 mg/day of prednisone, or an equivalent corticosteroid are excluded
• History of primary immunodeficiency
• History of organ transplant that requires therapeutic immunosuppression
• Taking daily probiotics (patients with last probiotic \> 4weeks prior to first dose of RMT are eligible)
• History of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive) who are on anti-retroviral treatment for \< 6 months and absolute CD4 count\<500 (patients with HIV not meeting these criteria are eligible)

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (10)

Dr. Amit Kulkarni

Phoenix, Arizona, 85338, United States

NOT YET RECRUITING

MNCCTN Essentia Health St. Joseph's Brainerd Medical Center

Brainerd, Minnesota, 56401, United States

RECRUITING

MNCCTN Essentia Health Deer River

Deer River, Minnesota, 56636, United States

RECRUITING

MNCCTN Essentia Health St. Mary's Detroit Lakes Clinic

Detroit Lakes, Minnesota, 56501, United States

RECRUITING

MNCCTN Essentia Health Duluth

Duluth, Minnesota, 55805, United States

RECRUITING

MNCCTN Essentia Health Fosston

Fosston, Minnesota, 56542, United States

RECRUITING

MNCCTN Essentia Health Hibbing Clinic

Hibbing, Minnesota, 55746, United States

RECRUITING

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

MNCCTN Essentia Health Sandstone

Sandstone, Minnesota, 550723, United States

RECRUITING

MNCCTN Essentia Health Virginia Clinic

Virginia, Minnesota, 55792, United States

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma of Lung; Lung Neoplasms

Interventions

Capsules; durvalumab; Cisplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Manish Patel, DO

  University of Minnesota, Division of Hematology, Oncology and Transplantation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Center Clinical Trials Office

CONTACT

612 624 2620; ccinfo@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: September 26, 2019
• Study Start: November 30, 2022
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 11, 2025

Record last verified: 2025-09

Locations

US (10)