mRNA-415 in Solid Tumors

What is the Purpose of this Study?

The purpose of the trial is to evaluate the safety and effects of an experimental personalized vaccine called mRNA-4157, as well as to identify the best dose for future studies, in patients who have had surgery to remove their cancer and are now considered disease-free after surgery. The study will also assess whether mRNA-4157 has any effect on the immune system; samples of blood will be taken to examine immune markers. Messenger ribonucleic acid (mRNA) is a naturally-occurring substance in the cells. Since the study’s mRNA-4157 vaccine is specifically made for patients and their cancer, it is also referred to as individualized neoantigen therapy. In Part A of the study, participants will be given mRNA-4157 by itself (monotherapy). In Part A2, mRNA-4157 will be given by itself and for a portion of this dosing, it will be given along with standard-of-care, post-surgery chemotherapy (adjuvant treatment).

Eligibility

* 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.

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.

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Where can I participate?

CS Cancer at The Angeles Clinic and Research Institute

More about this Clinical Trial

What is the full name of this clinical trial?

mRNA-4157-P101-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 Details

Disease Type/Condition

Brain and Nervous System, Breast, Colon, Lung, Other Endocrine System, Other Female Genital, Other Male Genital

Principal Investigator

Moyers, Justin

Co-Investigators

Cathie T Chung, Inderjit Mehmi, Iryna Singh, Justin Moyers, Kristopher Wentzel, Navid Hafez, Omid Hamid, Vi K. Chiu

Age Group

Adult

Phase

IRB Number

STUDY00003184

ClinicalTrials.gov ID

NCT03313778

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org