Clinical Trial - NCT03313778

Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Participants With Resected Solid Tumors and in Combination With Pembrolizumab in Participants 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 participants with resected solid tumors and in combination with pembrolizumab in participants 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

Number of Participants 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

Percent Change from Baseline of Biomarker Levels in Tumors at Day 50 [Time Frame: Baseline, 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: ]

Part C: Overall Response Rate (ORR): Number of Participants with Tumor Response (Partial or Complete) [Time Frame: Baseline through 30 days after the last dose of mRNA4157 and/or pembrolizumab] [Designated as safety issue: ]

Part C: Duration of Response (DoR) [Time Frame: Baseline through 30 days after the last dose of pembrolizumab] [Designated as safety issue: ]

Part C: Progression Free Survival (PFS) [Time Frame: Baseline through 30 days after the last dose of pembrolizumab] [Designated as safety issue: ]

Part C: Overall Survival (OS) [Time Frame: Baseline through 30 days after the last dose of pembrolizumab] [Designated as safety issue: ]

Estimated Enrollment: 142
Study Start Date: August 2017
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: June 2022
Arms Assigned Interventions

Experimental:Part A: Dose Escalation

Participants will receive a fixed applicable dose of mRNA-4157 administered via an intramuscular (IM) injection on Day 1 of each 21-day cycle for up to 9 cycles.
Biological:mRNA-4157
Personalized cancer vaccine, IM injection

Experimental:Part B: Dose Escalation

Participants will receive a fixed applicable dose of mRNA-4157 administered via an IM injection on Day 1 of each 21-day cycle for up to 9 cycles and fixed-dose of pembrolizumab via IV infusion on Day 1 of each 21-day cycle until progression, unacceptable toxicity, or up to 35 cycles (approximately 2 years of treatment), whichever is sooner.

Experimental:Part A: Dose Expansion

Participants will receive mRNA-4157 via IM injection at an applicable dose, identified during the dose escalation phase of the study, on Day 1 of each 21-day cycle for up to 9 cycles.

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

Participants will receive mRNA-4157 via IM injection at an applicable dose, identified during the dose escalation phase of the study, on Day 1 of each 21-day cycle for up to 9 cycles. Participants will also receive a fixed-dose of pembrolizumab via IV infusion on Day 1 of each 21-day cycle until progression, unacceptable toxicity, or up to 35 cycles (approximately 2 years of treatment), whichever is sooner.
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: Participants must have one of the histologically-confirmed solid malignancies listed below, must be clinically disease-free at study entry (that is, participants in the adjuvant setting). Participants 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 participant's medical record.
  • Part B: Participants must have one of the histologically- or cytologically-confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, have measurable disease at study entry defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1., and be considered suitable for treatment with pembrolizumab; in this study pembrolizumab will be considered an investigational study drug.

Participants with any of the following solid malignancies:

a. Non-small cell lung cancer (participants in Part B must either lack epidermal growth factor receptor (EGFR) sensitizing mutation or anaplastic lymphoma kinase (ALK) translocation per local test results or must have progressed on approved standard of care treatment for EGFR or ALK positive non-small cell lung cancer [NSCLC]) b. Small cell lung cancer c. Melanoma d. Bladder urothelial carcinoma e. Human papillomavirus-negative head and neck squamous cell carcinoma (HPV-ve HNSCC) f. Any solid malignancy known to be microsatellite instable (MSI) high/mismatch repair (MMR) deficient g. Any solid malignancy known to have a high tumor mutational load/burden

  • Part C: Participants must have one of the histologically- or cytologically confirmed unresectable (locally advanced or metastatic) solid malignancies listed below, 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.

1. Microsatellite stable (MSS)-CRC

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

3. Bladder urothelial carcinoma

  • Part D: Participants must have completed resected adjuvant melanoma and must be clinically disease-free at study entry. Participants 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 participant's medical record.
  • Parts A 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 and provide a biopsy suitable for the next generation sequencing (NGS) required for this study. An existing (archival) FFPE tumor sample may instead be used for NGS after discussing with medical monitor.
  • Participants must have resolution of toxic effect(s) from prior therapy to Grade 1 or less. Participants with Grade =2 neuropathy or alopecia are an exception to this criterion. If a participant received major surgery or radiation therapy of >30 gray (Gy), they must have recovered from the toxicity and/or complications from the intervention 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).
  • Participants with Performance Scale (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) PS
  • Life expectancy >12 weeks at Screening
  • Participants with adequate organ and marrow function
  • Parts A and D: Participant 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 (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

  • Prior PD-1/PD-L1 treatment is permitted for participants in Parts A, B, and D of this study, but only participants 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 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
  • Had a solid organ or allogeneic bone marrow transplant
  • Participants with a history of interstitial lung disease
  • An active infection requiring systemic therapy
  • A known history of human immunodeficiency virus (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
  • Participants 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 February 25, 2021