Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Neoplasms, Pancreatic Neoplasms
Conditions
Keywords
cancer, solid tumors, therapeutic vaccine, Pembrolizumab, PD1, PD-1, PDL1, PD-L1, KRAS, mRNA
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.
Interventions
BIOLOGICALV941
V941 administered IM, Q3W for 9 3-week cycles
BIOLOGICALPembrolizumab
Pembrolizumab 200 mg, IV for 35 3-week cycles
Sponsors
ModernaTX, Inc.
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 24 months | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinued study treatment due to an AE is reported. |
| Dose-Limiting Toxicities (DLTs) | Cycle 1 (Up to 21 days) | The following toxicities graded for severity using National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE), were considered a DLT if judged by the investigator to be possibly related to study investigational products: 1) Grade 4 nonhematologic toxicity (ie. not a laboratory finding). 2) Grade 4 hematologic toxicity lasting ≥ 7 days, except thrombocytopenia: 3) Grade 4 thrombocytopenia of any duration 4) Grade 3 thrombocytopenia associated with clinically significant bleeding 5) Any nonhematologic AE ≥ Grade 3 in severity, with some exceptions 6) Any Grade 3 or Grade 4 nonhematologic laboratory value that meets one of the study criteria 7) Febrile neutropenia Grade 3 or Grade 4 8) Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity. 9) Any treatment-related toxicity that causes participant to discontinue treatment during Cycle 1. 10) Grade 5 toxicity 11) Any other clinically significant toxicity judged to be a DLT by investigator. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 27 months | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | 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) | Mean change from baseline in the quantity of mutant KRAS specific T cells in blood was assessed using an enzyme linked immunosorbent spot (ELISpot) assay. ELISpot detects interferon gamma (IFN-g) producing T-cells in a participant's peripheral blood mononuclear cells (PBMC) in response to KRAS specific stimulation. Data are presented as spot forming cells (SFC) per 10\^6 PBMC. The mean change is reported. |
| Objective Response Rate (ORR) | Up to approximately 24 months | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by investigator is reported. |
| Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | 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) | The presence of mutant KRAS specific T cells (G12D, G12V, G13D, G12C, and Wild type) in blood was assessed using an enzyme linked immunosorbent spot (ELISpot) assay. ELISpot detects interferon gamma (IFN-g) producing T-cells in a participant's peripheral blood mononuclear cells (PBMC) in response to KRAS specific stimulation. Data are presented as spot forming cells (SFC) per 10\^6 PBMC. The post-treatment ELISpot readout for a cycle is reported. A cycle is 3 weeks. |
Other
| Measure | Time frame | Description |
|---|---|---|
| T-cell Receptor (TCR) Clonality and Diversity | Up to approximately 24 months | TCR clonality and diversity in the periphery and tumor. |
Countries
Australia, Hong Kong, New Zealand, Singapore, South Korea, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: V941 Monotherapy V941(mRNA-5671/V941) 1 mg administered intramuscularly (IM) once every 3 weeks (Q3W) for 9 3-week cycles | 3 |
| Part 1: V941 + Pembrolizumab V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, intravenous (IV) for 35 3-week cycles | 15 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles | 20 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles | 16 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) V941(mRNA-5671/V941) 1 mg administered IM Q3W for 9 3-week cycles and pembrolizumab 200 mg, IV for 35 3-week cycles | 16 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 12 | 13 | 10 | 11 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Sponsor's decision | 0 | 2 | 6 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 2 | 4 |
Baseline characteristics
| Characteristic | Part 1: V941 Monotherapy | Part 1: V941 + Pembrolizumab | Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Total |
|---|---|---|---|---|---|---|
| Age, Customized < 65 years | 2 Participants | 10 Participants | 9 Participants | 12 Participants | 6 Participants | 39 Participants |
| Age, Customized >= 65 years | 1 Participants | 5 Participants | 11 Participants | 4 Participants | 10 Participants | 31 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG = 0 | 2 Participants | 7 Participants | 1 Participants | 7 Participants | 6 Participants | 23 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG = 1 | 1 Participants | 8 Participants | 19 Participants | 9 Participants | 10 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 11 Participants | 19 Participants | 15 Participants | 16 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Primary Diagnosis Adenocarcinoma of the Colon | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Diagnosis Adenocarcinoma of the Pancreas | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 7 Participants |
| Primary Diagnosis Carcinoma Of Ampulla of Vater | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Diagnosis Cholangiocarcinoma | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Diagnosis Colorectal Cancer, not otherwise specified | 2 Participants | 7 Participants | 0 Participants | 16 Participants | 0 Participants | 25 Participants |
| Primary Diagnosis Lung Cancer, not otherwise specified | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Diagnosis Non-Small Cell Lung Cancer, not otherwise specified | 0 Participants | 0 Participants | 20 Participants | 0 Participants | 0 Participants | 20 Participants |
| Primary Diagnosis Pancreatic Cancer (Not Islets) | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 10 Participants | 13 Participants |
| Primary Diagnosis Rectal | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Prior Line of Therapy Fifth Line or Greater | 0 Participants | 3 Participants | 4 Participants | 4 Participants | 0 Participants | 11 Participants |
| Prior Line of Therapy First Line | 1 Participants | 2 Participants | 5 Participants | 0 Participants | 1 Participants | 9 Participants |
| Prior Line of Therapy Fourth Line | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 9 Participants |
| Prior Line of Therapy Second Line | 2 Participants | 5 Participants | 5 Participants | 4 Participants | 5 Participants | 21 Participants |
| Prior Line of Therapy Third Line | 0 Participants | 2 Participants | 5 Participants | 6 Participants | 7 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 12 Participants | 9 Participants | 9 Participants | 31 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 12 Participants | 8 Participants | 6 Participants | 7 Participants | 35 Participants |
| Sex: Female, Male Female | 1 Participants | 9 Participants | 13 Participants | 7 Participants | 9 Participants | 39 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 7 Participants | 9 Participants | 7 Participants | 31 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 12 / 15 | 1 / 1 | 13 / 20 | 12 / 16 | 13 / 16 |
| other Total, other adverse events | 3 / 3 | 15 / 15 | 0 / 1 | 20 / 20 | 16 / 16 | 15 / 16 |
| serious Total, serious adverse events | 1 / 3 | 6 / 15 | 0 / 1 | 5 / 20 | 7 / 16 | 9 / 16 |
Outcome results
Primary
Dose-Limiting Toxicities (DLTs)
The following toxicities graded for severity using National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE), were considered a DLT if judged by the investigator to be possibly related to study investigational products: 1) Grade 4 nonhematologic toxicity (ie. not a laboratory finding). 2) Grade 4 hematologic toxicity lasting ≥ 7 days, except thrombocytopenia: 3) Grade 4 thrombocytopenia of any duration 4) Grade 3 thrombocytopenia associated with clinically significant bleeding 5) Any nonhematologic AE ≥ Grade 3 in severity, with some exceptions 6) Any Grade 3 or Grade 4 nonhematologic laboratory value that meets one of the study criteria 7) Febrile neutropenia Grade 3 or Grade 4 8) Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity. 9) Any treatment-related toxicity that causes participant to discontinue treatment during Cycle 1. 10) Grade 5 toxicity 11) Any other clinically significant toxicity judged to be a DLT by investigator.
Time frame: Cycle 1 (Up to 21 days)
Population: The DLT evaluable population included all participants who received at least 1 dose of study treatment and were either observed for safety for 21 days after the first dose of treatment or experienced a DLT prior to 21 days after the first dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: V941 Monotherapy | Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: V941 + Pembrolizumab | Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinued study treatment due to an AE is reported.
Time frame: Up to approximately 24 months
Population: All participants who received at least 1 dose of study treatment. For AEs which occurred during Part 1 prior to switch-over, the information is in the Part 1: V941 Monotherapy column. For AEs which occurred during Part 1 subsequent to switch-over, the information is in the Part 1: V941 + Pembrolizumab column.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: V941 Monotherapy | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Part 1: V941 + Pembrolizumab | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Number of Participants Who Discontinued Study Treatment Due to an AE | 3 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Up to approximately 27 months
Population: All participants who received at least 1 dose of study treatment. For AEs which occurred during Part 1 prior to switch-over, the information is in the Part 1: V941 Monotherapy column. For AEs which occurred during Part 1 subsequent to switch-over, the information is in the Part 1: V941 + Pembrolizumab column.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: V941 Monotherapy | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part 1: V941 + Pembrolizumab | Number of Participants Who Experienced an Adverse Event (AE) | 15 Participants |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Number of Participants Who Experienced an Adverse Event (AE) | 20 Participants |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Number of Participants Who Experienced an Adverse Event (AE) | 16 Participants |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Number of Participants Who Experienced an Adverse Event (AE) | 16 Participants |
Secondary
Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells
Mean change from baseline in the quantity of mutant KRAS specific T cells in blood was assessed using an enzyme linked immunosorbent spot (ELISpot) assay. ELISpot detects interferon gamma (IFN-g) producing T-cells in a participant's peripheral blood mononuclear cells (PBMC) in response to KRAS specific stimulation. Data are presented as spot forming cells (SFC) per 10\^6 PBMC. The mean change is reported.
Time frame: 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)
Population: Participants with centrally-confirmed tumor KRAS mutations, with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study treatment. The number of participants analyzed indicates a pre-treatment ELISpot readout for a cycle and a post-treatment ELISpot readout for a cycle, which are required for a participant's data to be reported for a particular cycle. A cycle is 3 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 2 | 0.60 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 2 | 0.9 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 3 | 1.45 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Discontinuation Visit | 0.80 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.71 |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 3 | 1.15 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Discontinuation Visit | 1.55 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.35 |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 2 | 0.00 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Discontinuation Visit | 1.45 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.04 |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 1 | 1.00 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 2 | 0.00 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 1 | 1.08 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Discontinuation Visit | 0.77 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.08 |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 2 | -0.3 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Discontinuation Visit | -0.11 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.58 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 7 | 2.20 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 1 | 0.46 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.56 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 2 | 0.54 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.48 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 3 | 0.76 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.28 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 4 | 1.35 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.8 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 1 | 0.59 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.53 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 2 | 0.12 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.27 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 3 | 0.88 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.54 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 4 | 1.84 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.14 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 9 | 2.20 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 1 | 0.78 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.67 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 2 | 0.60 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.85 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 3 | 1.10 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.7 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 4 | 1.93 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.72 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 1 | 0.26 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.06 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 2 | 0.62 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.56 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 3 | 0.41 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.7 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 4 | 1.92 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.71 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 1 | -0.23 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.67 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 2 | 0.28 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.59 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 3 | 0.45 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.9 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 4 | 1.79 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.59 |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 7 | 2.33 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 + Pembrolizumab | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 9 | 1.95 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 4 | 2.04 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.17 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 4 | 1.32 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.54 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 4 | 1.28 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.76 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 6 | 1.06 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.73 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 6 | 1.45 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.67 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 6 | 1.64 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.43 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 6 | 0.90 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.63 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 4 | 1.64 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.26 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 6 | 1.10 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.07 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 4 | 1.50 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.56 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 6 | 1.61 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.51 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 6 | 1.75 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.95 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 6 | 1.62 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 4 | 1.68 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.91 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 4 | 1.84 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.71 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 6 | 1.12 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.54 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 4 | 0.79 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.9 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 4 | 0.94 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.26 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 4 | 0.25 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.22 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 6 | 0.55 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.05 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 6 | 0.99 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.08 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12C Cycle 4 | 1.85 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12V Cycle 4 | 2.25 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 4 | 1.78 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.44 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | Wild Type Cycle 4 | 0.76 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.66 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G12D Cycle 6 | 2.34 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.15 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Mean Change From Baseline in Quantity of Mutant KRAS Specific T Cells | KRAS G13D Cycle 4 | 1.26 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by investigator is reported.
Time frame: Up to approximately 24 months
Population: All participants who received at least 1 dose of study treatment. Per protocol, the 1 participant who switched over from Arm 1 Part 1: V941 Monotherapy to Arm 2 Part 1: V941 + Pembrolizumab was excluded from Arm 2 Part 1: V941 + Pembrolizumab for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: V941 Monotherapy | Objective Response Rate (ORR) | 0.0 Percentage of Participants |
| Part 1: V941 + Pembrolizumab | Objective Response Rate (ORR) | 6.7 Percentage of Participants |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Objective Response Rate (ORR) | 5.0 Percentage of Participants |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Objective Response Rate (ORR) | 12.5 Percentage of Participants |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Objective Response Rate (ORR) | 0.0 Percentage of Participants |
Secondary
Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells
The presence of mutant KRAS specific T cells (G12D, G12V, G13D, G12C, and Wild type) in blood was assessed using an enzyme linked immunosorbent spot (ELISpot) assay. ELISpot detects interferon gamma (IFN-g) producing T-cells in a participant's peripheral blood mononuclear cells (PBMC) in response to KRAS specific stimulation. Data are presented as spot forming cells (SFC) per 10\^6 PBMC. The post-treatment ELISpot readout for a cycle is reported. A cycle is 3 weeks.
Time frame: 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)
Population: Participants with centrally-confirmed tumor KRAS mutations, with a baseline scan that demonstrated measurable disease and who received at least 1 dose of study treatment. The number of participants analyzed indicates a pre-treatment ELISpot readout for a cycle and a post-treatment ELISpot readout for a cycle, which are required for a participant's data to be reported for a particular cycle. A cycle is 3 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 2 | 0.60 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 2 | 0.90 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 3 | 1.45 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Discontinuation Visit | 0.80 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.71 |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 3 | 1.15 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Discontinuation Visit | 1.55 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.35 |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 2 | 0.00 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Discontinuation Visit | 1.45 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.04 |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 1 | 1.00 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 2 | 0.00 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 1 | 1.08 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Discontinuation Visit | 0.92 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.87 |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 2 | 0.00 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 Monotherapy | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Discontinuation Visit | 0.54 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.34 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 7 | 2.20 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 1 | 0.56 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.45 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 2 | 0.59 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.49 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 3 | 0.76 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.28 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 4 | 1.35 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.8 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 1 | 0.59 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.53 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 2 | 0.12 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.27 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 3 | 0.88 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.54 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 4 | 1.84 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.14 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 9 | 2.20 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 1 | 0.78 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.67 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 2 | 0.60 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.85 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 3 | 1.10 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.7 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 4 | 1.93 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.72 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 1 | 0.65 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.49 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 2 | 0.62 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.56 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 3 | 0.91 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.87 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 4 | 1.92 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.71 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 1 | 0.24 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.54 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 2 | 0.49 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.6 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 3 | 0.86 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.6 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 4 | 1.79 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.59 |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 7 | 2.33 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 1: V941 + Pembrolizumab | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 9 | 1.95 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 4 | 2.04 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.17 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 4 | 1.64 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.59 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 4 | 1.53 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.02 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 6 | 1.60 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.12 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 6 | 2.34 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.4 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 6 | 1.64 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.43 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 6 | 1.38 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.01 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 4 | 2.07 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.18 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 6 | 1.93 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 1.29 |
| Part 2: Expansion Cohort 1 Non-small Cell Lung Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 4 | 2.08 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.48 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 6 | 2.30 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.53 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 6 | 2.24 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.68 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 6 | 1.77 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.21 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 4 | 2.12 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.89 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 4 | 1.94 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.67 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 6 | 1.88 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.24 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 4 | 1.56 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.47 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 4 | 1.70 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.82 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 4 | 1.48 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.2 |
| Part 2: Expansion Cohort 2 Colorectal Cancer (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 6 | 1.75 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.05 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 6 | 1.59 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.08 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12C Cycle 4 | 2.45 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12V Cycle 4 | 2.25 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 4 | 2.14 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.82 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | Wild Type Cycle 4 | 1.26 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.59 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G12D Cycle 6 | 2.34 Log10(IFN-g (SFC per 10^6 PBMC)) | Standard Deviation 0.15 |
| Part 2: Expansion Cohort 3 Pancreatic Adenocarcinoma (V941 + Pembrolizumab) | Presence of Mutant Kirsten Rat Sarcoma (KRAS) Specific T Cells | KRAS G13D Cycle 4 | 1.26 Log10(IFN-g (SFC per 10^6 PBMC)) | — |
Other Pre-specified
T-cell Receptor (TCR) Clonality and Diversity
TCR clonality and diversity in the periphery and tumor.
Time frame: Up to approximately 24 months
Population: Data were not collected for this outcome measure.