Clinical trial NCT03948763: A Study of mRNA-5671/V941 as Monotherapy and in Combination With Pembrolizumab (V941-001)
Official title: A Phase 1, Open-Label, Multicenter Study to Assess the Safety and Tolerability of mRNA-5671/V941 as a Monotherapy and in Combination With Pembrolizumab in Participants With KRAS Mutant Advanced or Metastatic Non-Small Cell Lung Cancer, Colorectal Cancer or Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Colorectal Neoplasms
Keywords: cancer
solid tumors
therapeutic vaccine
Pembrolizumab
PD1
PD-1
PDL1
PD-L1
KRAS
mRNA
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: ModernaTX, Inc.
First posted: 2019-05-14
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will determine the safety and tolerability and establish a preliminary recommended Phase 2 dose of V941(mRNA-5671/V941) as a monotherapy and in combination with pembrolizumab infusion.


Eligibility criteria: Inclusion Criteria:

Part 2 Only

- Has a histologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC), non-mismatch repair deficient/microsatellite instability-high tumors colorectal cancers (non-MSI-H CRC), or pancreatic adenocarcinoma, and confirmed HLA types HLA-A11:01 and/or HLA C08:02 (and/or potentially other additional HLA types to be specified).

NSCLC: Participants must have been tested for mutations affecting EGFR and/or anaplastic lymphoma kinase (ALK). Participants with ALK or epidermal growth factor receptor (EGFR)-positive NSCLC must have had recurrent or progressive disease (PD) after treatment with the corresponding inhibitor and current standard of care, in any sequence.

Non-MSI-H CRC: Participant tumors must have been locally tested for MSI and have been found to be non-MSI-H.

All

* Has a histologically confirmed advanced or metastatic KRAS 4MUT+ (G12D, G12V, G13D or G12C) (4 prevalent KRAS mutant antigens in solid tumors) solid tumor identified by local laboratory testing, and who have received, or been intolerant to, or ineligible for all treatment known to confer clinical benefit.
* A male participant must agree to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period.
* A female participant was not be pregnant, not breastfeeding, and at not be a woman of childbearing potential (WOCBP) OR if a WOCBP, agrees to follow study-approved contraceptive guidance during treatment period and for at least 120 days after the last dose of study intervention.
* Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* For Part 1 only: Cutaneous lesions can be considered in addition to imaging, but measurable disease should be defined by radiologic assessment.
* Have an evaluable archival tumor sample to submit for analysis. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
* Have adequate organ function
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

Exclusion Criteria:

* A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
* Has an active infection requiring therapy.
* Has a history of interstitial lung disease.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy.
* Has not fully recovered from any effects of major surgery or has evidence of detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered.
* Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, non-cytotoxic small molecule therapeutics within 5 half-lives (or 2 weeks, whichever is longer) prior to the first dose of study treatment, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any adverse events that were due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related adverse events).
* Has received a live-virus vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
* Has received hematopoietic colony-stimulating growth factors (eg, granulocyte-colony stimulating factor, granulocyte-macrophage-colony stimulating factor, macrophage colony stimulating factor) within 2 weeks prior to the first dose of study intervention.
* Discontinued from therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR; eg, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), CD137 (4-1BB, Tumor necrosis factor-receptor superfamily 9 \[TNFSF9\]), and OX 40 (TNFRSF4), due to a Grade 3 or higher immune-related adverse event (irAE).
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first dose of study intervention.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
* Has a known additional malignancy that is progressing or has required active treatment within the past 2 years.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV ribonucleic acid (RNA) \[qualitative\] is detected) infection.
* Has a known history of HIV.
* Has a known psychiatric or substance abuse disorder that would interfere with cooperating with the requirements of the study.
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.
* Has had an allogenic tissue/solid organ transplant.

Primary outcomes:
measure: Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Up to 21 days)
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 27 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells
timeFrame: Cycle 1 - Cycle 9 (a cycle is 3 weeks) and at the Discontinuation Visit (at the time of withdrawal or up to 30 weeks, whichever occurs first)
measure: Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells
timeFrame: Baseline and Cycle 1 - Cycle 9 (a cycle is 3 weeks) and at the Discontinuation Visit (at the time of withdrawal or up to 30 weeks, whichever occurs first)
Other outcomes:
measure: T-cell Receptor (TCR) Clonality and Diversity
timeFrame: Up to approximately 24 months
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center ( Site 1008)
state: Arizona
city: Duarte
country: United States
facility: City of Hope ( Site 1002)
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco ( Site 1006)
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven ( Site 1005)
state: Connecticut
city: Boston
country: United States
facility: Dana-Farber Cancer Institute (Boston) ( Site 1007)
state: Massachusetts
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada ( Site 1012)
state: Nevada
city: Nashville
country: United States
facility: Tennessee Oncology Nashville Drug Development Unit ( Site 7000)
state: Tennessee
city: San Antonio
country: United States
facility: START San Antonio ( Site 1004)
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Center - Temple ( Site 1009)
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC ( Site 1001)
state: Washington
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre ( Site 6000)
state: New South Wales
city: Bedford Park
country: Australia
facility: Southern Oncology Clinical Research Unit SOCRU ( Site 6002)
state: South Australia
city: Clayton
country: Australia
facility: Monash Health-Monash Medical Centre ( Site 6001)
state: Victoria
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital ( Site 2002)
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital ( Site 2001)
city: Songpagu
country: Korea, Republic of
facility: Asan Medical Center ( Site 0802)
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0801)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital ( Site 0800)
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research (Christchurch) ( Site 6501)
state: Canterbury
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 6500)
city: Singapore
country: Singapore
facility: National University Hospital ( Site 3006)
state: Central Singapore
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore ( Site 3005)
state: Central Singapore
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital ( Site 3007)
state: Central Singapore
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 4002)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 4000)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 4001)
Study officials:
affiliation: Merck Sharp and Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: