Clinical Trial - NCT03313778

Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects With Resected Solid Tumors and in Combination With Pembrolizumab in Subjects With Unresectable Solid Tumors

Recruiting

Sponsor: ModernaTX, Inc.

Collaborators: Merck Sharp & Dohme Corp.

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03313778

Protocol Info

Short Description: Phase 1 MRNA-4157 in Solid Tumors
Long Description: A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects with Resected Solid Tumors and in Combination with Pembrolizumab in Subjects with Unresectable Solid Tumors
MGH Status: Open
Sponsor: Moderna Therapeutics
Disease Program: Phase I

Next Steps


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Purpose

The purpose of this study is to assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors, and in combination with pembrolizumab in subjects with unresectable solid tumors.
Condition Title Intervention Phase
Solid Tumors mRNA-4157 Pembrolizumab Phase 1
Study Type Interventional
Official Title A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects With Resected Solid Tumors and in Combination With Pembrolizumab in Subjects With Unresectable Solid Tumors

Primary Outcome Measures

Percentage of subjects with dose limiting toxicities [Time Frame: Parts A and B dose escalation Days 1-21] [Designated as safety issue: ]

Percentage of subjects with adverse events [Time Frame: Part A: baseline through 100 days after last mRNA-4157 dose; Parts B, C, and D: baseline through 90 days after last pembrolizumab dose] [Designated as safety issue: ]


Secondary Outcome Measures

Percentage change from baseline of biomarker levels in tumors [Time Frame: Baseline through Day 50] [Designated as safety issue: ]

Antigen-specific T-cell responses in peripheral blood [Time Frame: Baseline through 100 days after last mRNA-4157 dose] [Designated as safety issue: ]

Parts A and D: Relapse free survival (RFS): time between the date of first dose of mRNA-4157 and either radiological disease relapse, clinical/symptomatic disease relapse as assessed by the Investigator or death (whichever is sooner) [Time Frame: Baseline through 2 years after first mRNA-4157 dose] [Designated as safety issue: ]

Parts B and C: Overall Response Rate (ORR): Percentage of patients with tumor response (partial or complete) [Time Frame: Baseline through 30 days after the last dose of pembrolizumab] [Designated as safety issue: ]

Parts B and C: Duration of Response (DoR): time from first tumor response (partial or complete) until either radiological disease progression, clinical/symptomatic disease progression or death (whichever is sooner) [Time Frame: Baseline through 30 days after the last dose of pembrolizumab] [Designated as safety issue: ]

Parts B and C: Progression free survival (PFS): time between the date of first dose of pembrolizumab and the date of either radiological disease progression, clinical/symptomatic disease progression or death (whichever is sooner) [Time Frame: Baseline through 30 days after the last dose of pembrolizumab] [Designated as safety issue: ]

Parts B and C: Overall survival (OS): time between the date of the first dose of study drug and the date of death due to any cause [Time Frame: Baseline through 30 days after the last dose of pembrolizumab] [Designated as safety issue: ]

Parts A, B, C, and D: Percent change in blood borne biomarkers (for example ctDNA and circulating cytokines) and potential correlation to clinical outcome [Time Frame: Baseline through 30 days after the last dose of pembrolizumab] [Designated as safety issue: ]

Parts B, C, and D: Serum concentration of pembrolizumab [Time Frame: Pre-infusion until 30 days post last dose of pembrolizumab] [Designated as safety issue: ]

Parts B, C, and D: Percentage of patients with anti-drug-antibodies (ADA's) to pembrolizumab [Time Frame: Pre-infusion until 30 days post last dose of pembrolizumab] [Designated as safety issue: ]

Estimated Enrollment: 90
Study Start Date: August 2017
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: December 2020
Arms Assigned Interventions

Experimental:Part A: Dose Escalation

mRNA-4157
Biological:mRNA-4157
Personalized cancer vaccine

Experimental:Part B: Dose Escalation

mRNA-4157 + pembrolizumab

Experimental:Part B: Dose Expansion

mRNA-4157 + pembrolizumab

Experimental:Part B, C, and D: Dose Expansion

mRNA-4157 + pembrolizumab
Biological:Pembrolizumab
intravenous infusion

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Male or female, = 18 years old with the ability to understand and provide signed and witnessed informed consent, and agree to comply with protocol requirements
  • Part A: Subjects must have one of the histologically-confirmed solid malignancies listed below, must be clinically disease-free at study entry (i.e., subjects in the adjuvant setting). Subjects will be permitted to complete any standard of care adjuvant therapy prior to study entry, and those not eligible for any standard of care adjuvant treatment, or who decline such treatment, are permitted to consent to this study, as long as all treatment options have been transparently disclosed and documented in the Subject's medical record
  • Part B: Subjects must have one of the histologically- or cytologically-confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, AND 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.

Subjects with any of the following solid malignancies:

a. Non-small cell lung cancer (subjects in Part B must either lack EGFR sensitizing mutation or ALK translocation per local test results, or must have progressed on approved standard of care treatment for EGFR or ALK positive NSCLC) b. Small cell lung cancer c. Melanoma d. Bladder urothelial carcinoma e. Human papillomavirus-negative HNSCC f. Any solid malignancy known to be MSI high/MMR deficient per local test results, including but not limited to: CRC, stomach adenocarcinoma, esophageal adenocarcinoma and endometrial cancer

  • Part C: Subjects must have one of the histologically- or cytologically confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, AND must not have received prior anti-PD-1/PD-L1 therapy, AND must have measurable disease at study entry defined by RECIST 1.1

1. MSS-CRC

2. HPV negative metastatic or recurrent HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx

3. Bladder urothelial carcinoma

  • Part D: Subject must have completed resected adjuvant melanoma and must be clinically disease-free at study entry (i.e., subjects in the adjuvant setting). Subjects will be permitted to complete any standard of care adjuvant therapy prior to study entry, and those not eligible for any standard of care adjuvant treatment, or who decline such treatment, are permitted to consent to this study, as long as all treatment options have been transparently disclosed and documented in the subject's medical record
  • Parts A and D: subjects must have a FFPE tumor sample available (e.g., from their prior surgery) that is suitable for the next generation sequencing (NGS) required for this study.
  • Parts B and C: subjects must have at least 1 lesion amenable to the mandatory fresh tumor biopsy at study entry and provide a biopsy suitable for the NGS required for this study. An existing (archival) FFPE tumor sample may instead be used for NGS after discussing with medical monitor
  • Subjects must have resolution of toxic effect(s) from prior therapy to Grade 1 or less. Subjects with = Grade 2 neuropathy or alopecia are an exception to this criterion. If a subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention to Grade 1 or less
  • Subject 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)
  • Subjects with PS of 0 or 1 on the ECOG Performance Scale
  • Life expectancy > 12 weeks at Screening
  • Subjects with adequate organ and marrow function
  • Parts A and D: Subject must consent to required apheresis procedure and meet additional inclusion criteria per local institutional apheresis procedure

Exclusion Criteria:

  • Treatment with any of the following:

1. Any investigational agents, anti-cancer monoclonal antibody, anti-cancer therapeutic vaccine, immunostimulant (e.g. 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 G-CSF, 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

  • Prior PD-1/PD-L1 treatment is permitted for subjects in Parts A, B and D of this study, but only subjects who have progressed on their prior PD-1/PD-L1 treatment without a partial or complete response, and without discontinuing for drug-related toxicity are eligible
  • Active central nervous system metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
  • Has a diagnosis of immunodeficiency
  • Any clinically-significant cardiac disease defined as New York Heart Association class III or IV within the past 6 months of Screening, unless, in the opinion of the Investigator, the disease is well-controlled
  • A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject 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
  • Had a solid organ or allogeneic bone marrow transplant
  • Subjects with a history of interstitial lung disease
  • An active infection requiring systemic therapy
  • A known history of HIV
  • Known active Hepatitis B or Hepatitis C
  • 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
  • Subjects participating in apheresis; mandatory in the Part A apheresis expansion phase cohort and Part D (optional for other study parts), must not meet any of the exclusion criteria on any day when apheresis is performed, either protocol specific apheresis criteria, or per local institutional apheresis protocol.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03313778

Locations

  • United States, Arizona
    • University of Arizona Tucson, Arizona, United States, 85721
  • United States, Florida
    • Florida Cancer Specialists Sarasota, Florida, United States, 34232
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
  • United States, New Jersey
    • John Theurer Cancer Center Hackensack, New Jersey, United States, 07601
  • United States, New York
    • NYU Langone New York, New York, United States, 10016
  • United States, North Carolina
    • Duke Cancer Institute Durham, North Carolina, United States, 27710
  • United States, Tennessee
    • Sarah Cannon Research Institute, Tennessee Oncology Nashville, Tennessee, United States, 37203

Sponsors and Collaborators

ModernaTX, Inc.

Merck Sharp & Dohme Corp.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03313778
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by ModernaTX, Inc.:

mRNA-4157

Personalized cancer vaccine

PCV

pembrolizumab

Moderna

Additional relevant MeSH terms:

Neoplasms

Pembrolizumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on October 14, 2020