Bladder Carcinoma, Breast Cancer, Colon Carcinoma, Melanoma, Non-Small Cell Lung Carcinoma, Prostate Cancer, Renal Cell Carcinoma, Upper GI Tract Carcinoma
Conditions
Keywords
Urinary Bladder Neoplasms, Breast Neoplasms, Renal Cell carcinoma, Melanoma, Prostatic Neoplasms, Colonic Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Urinary Bladder Diseases, Urologic Diseases, Breast Diseases, Skin Diseases, Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type, Adenocarcinoma, Kidney Neoplasms, Kidney Diseases, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms, Nerve Tissue, Nevi and Melanomas, Genital Neoplasms, Male Genital Diseases, Male, Prostatic Diseases, Colorectal Neoplasms, Intestinal Neoplasms
Brief summary
This is a two-part study to test the safety, tolerability, and immune response for V934/V935 vaccine using a new prime-boost regimen in participants with selected solid tumors.
Detailed description
Two vaccines will be administered: V934-electroporation (EP) either low dose (LD) or high dose (HD), and V935 either LD or HD. In Part A, participants will be assigned to V935 vaccine alone or in combination with V934-EP. Part B will be an optional part of the study, offering V934-EP vaccine booster to participants who were enrolled in Part A.
Interventions
BIOLOGICALV935
A 0.5 mL vaccine administered IM every 2 weeks as either a LD (1 x 10\^9 vector genomes/mL) or a HD (1 x 10\^11 vector genomes/mL).
BIOLOGICALV934-EP
A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part A * Participant has one of the selected solid tumors with no distant metastases, and is more than 8 weeks from completion of definitive therapy with intention to cure. Selected Solid Tumors: Stage I to III non-small cell lung carcinoma (NSCLC); Stage III breast cancer; Stage IIB or III melanoma; Stage II or III upper gastrointestinal tract carcinoma (e.g., esophagus, stomach, gallbladder, pancreas); Stage III colon carcinoma; Stage II, III, or IV (M0 only) renal cell carcinoma; Stage II, III, or IV (M0 only) bladder carcinoma; clinically-localized prostate carcinoma * Participant has adequate organ function. * Female participant of childbearing potential has a negative serum pregnancy test within 3 days of study enrollment.
Exclusion criteria
Part A * Participant has known hypersensitivity to any component of study vaccine. * Participant has a history of clinically significant cardiac conditions, including cardiac arrhythmias which have not been controlled within the last 3 months, unstable angina, myocardial infarction (within the last 3 months), or New York Heart Association (NYHA) Class III or IV congestive heart failure. Participant must have no clinically significant electrocardiogram (ECG) abnormalities and not have a pacemaker or cardioverter/defibrillator implanted. * Participant has undergone splenectomy or has any history of autoimmune disorder. * Participant has received immunosuppressive treatment within 1 month prior to enrollment. * Participant has known acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections. * Participant has an acute infection requiring intravenous antibiotic, antiviral or antifungal agents within 2 weeks of study entry. * Participant is pregnant or breastfeeding, or expecting to conceive at any time during the study or within 1 year after receiving the last vaccination. * Participant is known to be Human Immunodeficiency Virus (HIV)-seropositive. * Participant has known history of Hepatitis B or C or active Hepatitis A. * Participant has been vaccinated for any disease or for prophylaxis within 1 month prior to the first vaccination. * The participant has been diagnosed with Systemic Lupus Erythematosus (SLE) Inclusion Criteria Part B * Participant must have completed their respective vaccination Treatment Group regimen for Part A of this study. * Participant must have completed a ≥12 week safety observation period prior to receiving their first V934-EP boost.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicity (DLT) | Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period | DLT was defined as a vaccine- or EP-related adverse event (AE) including the following: Hematological (Grade 3 neutropenia with fever, Grade 4 neutropenia ≥5 days, Grade 4 thrombocytopenia) or non-hematological AE, Grade 3, 4 or 5 with the exception of Grade 3 nausea, vomiting, diarrhea or serum glutamic oxaloacetic transaminase (SGOT) elevation, alopecia, Grade 3/4 creatinine phosphokinase (CPK) elevation or inadequately treated hypersensitivity. Any Grade 3/4 related AE that failed to return to ≤Grade 1 or baseline within 14 days was also considered a DLT. |
| Number of Participants With Adverse Events (AEs) | Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period | This analysis includes the number of participants with AEs and serious AEs (SAEs) during the Treatment Period plus the Acute Follow-up (FU) Period (up to 30 days following last vaccination). An AE was defined as any unfavorable or unintended change in the structure, function or chemistry of the body temporally associated with the use of the product, whether or not considered related to the product, including any worsening of a preexisting condition which was temporally associated with the product. An SAE was defined as an AE resulting in death, was life-threatening, resulted in or prolonged hospitalization, was a congenital anomaly, a cancer, an overdose or other important medical event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Immunologic Response to V934/V935 (Immunologic Response Rate) | From pre-vaccination to Week 69 | An Enzyme-Linked Immunosorbent Spot (ELISPOT) assay was planned to be used to demonstrate a cell mediated immune response to V935 and/or V934 in vaccinated participants. Collection of Peripheral Blood Mononuclear Cells (PBMCs) and serum took place at baseline (Screening and pre-vaccination Day 1), and various time points post vaccination across the three distinct regimens to be tested. A positive immune response was to be defined by a minimum number of spot-forming cells per million PBMC (SFC/10\^6 PBMCs) for the antigen well and a minimum n-fold increase in the antigen well over the control well. |
Participant flow
Recruitment details
V935 alone or in combination with V934 was administered to 37 participants with selected solid tumors in Part A.
Pre-assignment details
Of the 37 participants who were enrolled in Part A, 32 participants completed and were eligible to enroll in the optional extension study Part B. There were 28 participants who elected to enroll in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: V935 LD Two IM injections of V935 low dose (LD), 1 given every other week over a 3-week period. | 3 |
| Part A: V934 LD(3)+V935 LD Three electroporation (EP) injections of V934 (LD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (LD) were administered, 1 given every other week over a 3-week period. | 3 |
| Part A: V935 HD Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period. | 10 |
| Part A: V934 HD(3)+V935 HD Three EP injections of V934 (HD) were administered, 1 given every other week over a 5-week period. Following a 4 week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period. | 11 |
| Part A: V934 HD(5)+V935 HD Five EP injections of V934 (HD) were administered, 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) were administered, 1 given every other week over a 3-week period. | 10 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A | Disease progression | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B | Disease progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Part B | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A: V935 LD | Part A: V934 LD(3)+V935 LD | Part A: V935 HD | Part A: V934 HD(3)+V935 HD | Part A: V934 HD(5)+V935 HD | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 70.0 Years STANDARD_DEVIATION 9.5 | 70.0 Years STANDARD_DEVIATION 6.2 | 63.8 Years STANDARD_DEVIATION 10 | 58.8 Years STANDARD_DEVIATION 11.7 | 60.2 Years STANDARD_DEVIATION 11.7 | 62.4 Years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 4 Participants | 4 Participants | 1 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 6 Participants | 7 Participants | 9 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 8 / 10 | 11 / 11 | 10 / 10 | 1 / 1 | 1 / 2 | 3 / 7 | 8 / 9 | 7 / 9 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 2 / 10 | 2 / 11 | 1 / 10 | 0 / 1 | 0 / 2 | 0 / 7 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
This analysis includes the number of participants with AEs and serious AEs (SAEs) during the Treatment Period plus the Acute Follow-up (FU) Period (up to 30 days following last vaccination). An AE was defined as any unfavorable or unintended change in the structure, function or chemistry of the body temporally associated with the use of the product, whether or not considered related to the product, including any worsening of a preexisting condition which was temporally associated with the product. An SAE was defined as an AE resulting in death, was life-threatening, resulted in or prolonged hospitalization, was a congenital anomaly, a cancer, an overdose or other important medical event.
Time frame: Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period
Population: All Participants as Treated (APaT) population; all participants who received at least one vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: V935 LD | Number of Participants With Adverse Events (AEs) | 3 Participants |
| Part A: V934 LD(3)+V935 LD | Number of Participants With Adverse Events (AEs) | 3 Participants |
| Part A: V935 HD | Number of Participants With Adverse Events (AEs) | 8 Participants |
| Part A: V934 HD(3)+V935 HD | Number of Participants With Adverse Events (AEs) | 11 Participants |
| Part A: V934 HD(5)+V935 HD | Number of Participants With Adverse Events (AEs) | 10 Participants |
| Part B: V935 LD/V934 Booster | Number of Participants With Adverse Events (AEs) | 1 Participants |
| Part B: V934 LD(3)+V935 LD/V934 Booster | Number of Participants With Adverse Events (AEs) | 1 Participants |
| Part B: V935 HD/V934 Booster | Number of Participants With Adverse Events (AEs) | 3 Participants |
| Part B: V934 HD(3)+V935 HD/V934 Booster | Number of Participants With Adverse Events (AEs) | 8 Participants |
| Part B: V934 HD(5)+V935 HD/V934 Booster | Number of Participants With Adverse Events (AEs) | 7 Participants |
Primary
Number of Participants With Dose-Limiting Toxicity (DLT)
DLT was defined as a vaccine- or EP-related adverse event (AE) including the following: Hematological (Grade 3 neutropenia with fever, Grade 4 neutropenia ≥5 days, Grade 4 thrombocytopenia) or non-hematological AE, Grade 3, 4 or 5 with the exception of Grade 3 nausea, vomiting, diarrhea or serum glutamic oxaloacetic transaminase (SGOT) elevation, alopecia, Grade 3/4 creatinine phosphokinase (CPK) elevation or inadequately treated hypersensitivity. Any Grade 3/4 related AE that failed to return to ≤Grade 1 or baseline within 14 days was also considered a DLT.
Time frame: Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period
Population: Evaluable patients who completed all scheduled vaccinations were included in the DLT analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: V935 LD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: V934 LD(3)+V935 LD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: V935 HD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: V934 HD(3)+V935 HD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part A: V934 HD(5)+V935 HD | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: V935 LD/V934 Booster | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: V934 LD(3)+V935 LD/V934 Booster | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: V935 HD/V934 Booster | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: V934 HD(3)+V935 HD/V934 Booster | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
| Part B: V934 HD(5)+V935 HD/V934 Booster | Number of Participants With Dose-Limiting Toxicity (DLT) | 0 Participants |
Secondary
Number of Participants With Immunologic Response to V934/V935 (Immunologic Response Rate)
An Enzyme-Linked Immunosorbent Spot (ELISPOT) assay was planned to be used to demonstrate a cell mediated immune response to V935 and/or V934 in vaccinated participants. Collection of Peripheral Blood Mononuclear Cells (PBMCs) and serum took place at baseline (Screening and pre-vaccination Day 1), and various time points post vaccination across the three distinct regimens to be tested. A positive immune response was to be defined by a minimum number of spot-forming cells per million PBMC (SFC/10\^6 PBMCs) for the antigen well and a minimum n-fold increase in the antigen well over the control well.
Time frame: From pre-vaccination to Week 69
Population: Planned analysis for the secondary endpoint of Immunologic Response Rate was not performed due to study de-prioritization.