Clinical trial NCT03313778: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors
Official title: A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumors
Keywords: mRNA-4157
PCV
pembrolizumab
Moderna
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-10-18
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone and in combination in participants with solid tumors.

Detailed description: This is a multi-part, dose-escalation study of mRNA-4157 monotherapy in participants with resected solid tumors (Part A), mRNA-4157 monotherapy lead-in and then in combination with standard of care (SoC) adjuvant chemotherapy followed by mRNA-4157 monotherapy in participants with resected pancreatic ductal adenocarcinoma (PDAC) (Part A2), mRNA-4157 in combination with pembrolizumab in participants with both unresectable (locally advanced or metastatic) solid tumors (Parts B and C) and adjuvant resected cutaneous melanoma (Part D), and mRNA-4157 in combination with pembrolizumab and SoC chemotherapy in peri-operative setting in participants with non-squamous non-small cell lung cancer (NSCLC) (Part E1), squamous cell NSCLC (Part E2), and gastric/ gastroesophageal (GEJ) cancer (Part E3). Parts A and B will include a dose escalation phase of the study to identify doses of mRNA-4157 for the expansion phase of the study. Doses of mRNA-4157 will be administered to participants in a dose escalation regimen. Participants in Parts A2, B, C, D, E1, E2 and E3 dose expansion phase will receive mRNA-4157 at a recommended dose for expansion.

Eligibility criteria: Inclusion Criteria:

* Parts A, A2, and D: Participants must be clinically disease-free at study entry (that is, participants in the adjuvant setting).
* Part B: Participants must have one of the histologically- or cytologically-confirmed unresectable (locally advanced or metastatic) protocol-specified solid malignancies, have measurable disease at study entry defined by RECIST 1.1., and be considered suitable for treatment with pembrolizumab; in this study pembrolizumab will be considered an investigational study drug.
* Part C: Participants must have one of the histologically- or cytologically confirmed unresectable (locally advanced or metastatic) protocol-specified solid malignancies, must not have received prior anti-programmed cell death protein 1 (PD-1)/programmed death -ligand 1 (PD-L1) therapy, and must have measurable disease at study entry defined by RECIST 1.1.
* Part A2: Participants with histologically confirmed PDAC who have undergone complete macroscopic resection(that is, R0 - no cancer cells within 1 mm of all resection margins or R1 - cancer cells present within 1 mm of one or more resection margins) who had no evidence of metastatic disease with adequate recovery from surgery to receive adjuvant therapy.
* Parts E1 and E2: Participants with untreated histologically/cytologically confirmed Stage II-IIIB NSCLC (per AJCC version 8) that is considered resectable of non-squamous (adenocarcinoma only) or squamous cell carcinoma histology, absence of major associated pathologies that increase the surgery risk to an unacceptable level, must have a tumor tissue sample available for NGS and PD-L1 IHC testing as defined in the Laboratory Manual.
* Part E3: Participants with untreated, locally advanced surgically resectable, histologically/cytologically confirmed, gastric/GEJ adenocarcinoma, as defined by a primary lesion that is T3 or greater or with the presence of any positive clinical nodes (N+) and without evidence of metastatic disease, measurable disease according to RECIST version 1.1, absence of major associated pathologies that increase the surgery risk to an unacceptable level, must have a tumor tissue sample available for NGS and PD-L1 IHC testing as defined in the Laboratory Manual.
* Part D: Participants with completely resected Stage II, III or IV cutaneous melanoma.
* Parts A, A2, and D: Participants must have a formalin-fixed paraffin embedded (FFPE) tumor sample available (for example, from their prior surgery) that is suitable for the next generation sequencing (NGS) required for this study.
* Parts B and C: Participants must have at least 1 lesion amenable to the mandatory fresh tumor biopsy at study entry.
* Participants must have resolution of toxic effect(s) (as specified in the protocol) from prior therapy to Grade 1 or less.
* Participant is willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug (male and female participants of childbearing potential), or for a specified time after the last dose of SoC chemotherapy per SoC product labeling, whichever is later.
* Participants with Performance Scale (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) PS.

Exclusion Criteria:

* Treatment with any of the following:

  1. Any investigational agents, anti-cancer monoclonal antibody, anti-cancer therapeutic vaccine, immunostimulant (for example, IL-2), or study drugs from a previous clinical study within 4 weeks of the first dose of mRNA-4157 or pembrolizumab (note only a 2 week wash out is required from prior pembrolizumab treatment)
  2. Any chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of the first dose of mRNA-4157 or pembrolizumab
  3. Live-virus vaccination within 30 days of the first dose of mRNA-4157 or pembrolizumab. Seasonal flu vaccines that do not contain live virus are permitted.
  4. Any systemic steroid therapy or other form of immunosuppressive therapy within 7 days of the first dose of mRNA-4157 or pembrolizumab
  5. Transfusion of blood products (including platelets or red blood cells \[RBCs\]) or administration of colony stimulating factors (including granulocyte colony stimulating factor \[G-CSF\], granulocyte/macrophage colony stimulating factor \[GM-CSF\], or recombinant erythropoietin) within 1 week of the NGS blood sample during screening, and 4 weeks of the first dose of mRNA-4157 or pembrolizumab
* A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator
* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
* Previously identified hypersensitivity to components of the formulations used in this study
* Known additional malignancy that is progressing or requires active treatment, exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone curative therapy, or in situ cervical cancer.

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Part A and A2: Baseline through 100 days after last mRNA-4157 dose; Parts B, C, D, E1, E2, and E3: Baseline through 90 days after last pembrolizumab dose
Secondary outcomes:
measure: Part C: Overall Response Rate (ORR): Number of Participants with Tumor Response (Partial or Complete)
timeFrame: Baseline through disease progression by Response Evaluation Criteria of Solid Tumors Version 1.1 (RECIST 1.1), start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)
measure: Part C: Duration of Response (DoR)
timeFrame: Baseline through disease progression by RECIST 1.1, start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)
measure: Part C: Progression Free Survival (PFS)
timeFrame: Baseline through disease progression by RECIST 1.1, start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)
measure: Part C: Overall Survival (OS)
timeFrame: Baseline to death of any cause (up to approximately 3 years)
measure: Part A2: Recurrence-free Survival (RFS)
timeFrame: Baseline up to 2 years
measure: Parts A2, E1, E2, and E3: Number of Participants with Presence or Absence of Circulating Tumor DNA (ctDNA)
timeFrame: Baseline up to 2 years
measure: Parts E1 and E2: Event-free Survival (EFS)
timeFrame: Baseline up to 2 years
measure: Part E3: EFS
timeFrame: Baseline up to 2 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Angeles Clinic and Research Institute
state: California
city: Washington
country: United States
facility: The George Washington Cancer Center
state: District of Columbia
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Cancer
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center, John Theurer Cancer Center
state: New Jersey
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI, Oncology Partners
state: Tennessee
city: Dallas
country: United States
facility: UT Southwest Medical Center
state: Texas
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincents Hospital Sydney
state: New South Wales
city: Randwick
country: Australia
facility: Scientia Clinical Research Ltd
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital-Cnr Hawkesbury and Darcy Road
state: New South Wales
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Frankston
country: Australia
facility: PASO Medical
state: Victoria
city: Perth
country: Australia
facility: One Clinical Research Perth
state: Western Australia
city: Chiba
country: Japan
facility: National Cancer Center East
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation For Cancer Research
city: Dundee
country: United Kingdom
facility: NHS Tayside
state: Scotland
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: Royal Mardsen London
city: London
country: United Kingdom
facility: University College of London
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Mardsen Sutton
Study officials:
References: