Neoplasms
Conditions
Keywords
Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand 2 (PD-L2), PD-1, PDL1, PD-L1, PD-L2
Brief summary
This is a safety, efficacy, and pharmacokinetics (PK) study of vibostolimab (MK-7684) as monotherapy and in combination with pembrolizumab (MK-3475) or pembrolizumab plus pemetrexed and carboplatin in adults with metastatic solid tumors for which there is no available therapy that is expected to convey clinical benefit. Part A of this study is a dose escalation and confirmation phase to estimate the recommended Phase 2 dose (RPTD) for vibostolimab monotherapy or in combination with pembrolizumab, pemetrexed, and carboplatin. Part A will also evaluate the anti-tumor activity of vibostolimab in combination with pembrolizumab plus pemetrexed and carboplatin in participants with non-small cell lung cancer (NSCLC) and vibostolimab (at two dose levels) in combination with pembrolizumab in Japanese participants with gastric cancer. Part B will evaluate the anti-tumor activity of vibostolimab at the RPTD when used as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors in a non-randomized study design. Part B will also evaluate 2 doses of vibostolimab in combination with pembrolizumab in participants with programmed death 1 (PD-1) treatment naïve cancer using a 1:1 randomized study design. Part B is expanded with Amendment 11 to include an additional arm that will compare the safety and PK of a fixed dose of pembrolizumab/vibostolimab coformulation (MK-7684A) to vibostolimab in combination with pembrolizumab administered as separate intravenous infusions. Part A is expanded with Amendment 12 to include an additional arm that will compare the safety and PK of vibostolimab plus pembrolizumab plus the investigator's choice of platinum agent (carboplatin or cisplatin), and etoposide. Part B is expanded with Amendment 12 to include evaluation of efficacy of vibostolimab plus pembrolizumab plus the investigator's choice of platinum agent (carboplatin or cisplatin), and etoposide and efficacy of pembrolizumab/vibostolimab coformulation in participants from mainland China. The primary hypotheses are that vibostolimab administered as monotherapy or in combination with pembrolizumab is safe and tolerable when administered at the RPTD and that pembrolizumab/vibostolimab coformulation is safe and tolerable when administered as a fixed dose.
Interventions
BIOLOGICALvibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
BIOLOGICALpembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
DRUGpemetrexed
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
DRUGcarboplatin
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4
BIOLOGICALpembrolizumab/vibostolimab coformulation
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
DRUGcisplatin
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4
DRUGetoposide
Administered as an IV infusion on Days 1-3 of 21-day infusion Cycles 1-4
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
* For Part A participants enrolled prior to Amendment 7, must have a histologically or cytologically confirmed metastatic solid tumor for which there is no available therapy that is expected to convey clinical benefit * For Part A Japanese cohort added with Amendment 7: Must reside in Japan and be of Japanese descent and have adenocarcinoma of the stomach and/or gastric-esophageal junction (GEJ) that is considered inoperable and that has received, and progressed on, at least 1 prior chemotherapy regimen or human epidermal growth factor receptor 2 (HER2)/neu-targeted approved therapy (if HER2/neu-positive). In both cases, participants may be untreated or could have received and progressed on 1 prior regimen, but must not have received prior anti-PD-1/PD-L1 therapy * For Part A participants with non-small cell lung cancer (NSCLC) added with Amendment 7: Must have a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b per current American Joint Committee on Cancer criteria, edition 8) non-squamous NSCLC * For Part B China participants added with Amendment 12. Must have a histologically or cytologically confirmed metastatic solid tumor for which no more than 2 prior lines of therapy were administered and there is no available therapy that is expected to convey clinical benefit AND be Chinese from mainland China * For Parts A and B: Has histologically or cytologically confirmed metastatic solid tumor * Has measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) * Has an Eastern Cooperative Oncology Group performance status of 0 to 1 * Females must not be pregnant * Women of childbearing potential and male participants must agree to use adequate contraception for the course of the study * Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion) * For Chinese participants enrolled as part of Amendment 12. No tumor tissue samples will be collected
Exclusion criteria
* Has had chemotherapy, radiation, biological cancer therapy or major surgery within 4 weeks prior to the first dose of study treatment * Has not recovered to Common Toxicity Criteria for Adverse Events Grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks prior to the first dose of study treatment * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment * Has received previous treatment with another agent targeting the T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (TIGIT) receptor * Has received previous treatment with an immunomodulatory agent (e.g., anti-programmed cell death 1, anti-programmed cell death ligand 1 or cytotoxic T-lymphocyte-associated protein 4) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event * Is expected to require any other form of antineoplastic therapy while participating in the trial * Is on chronic systemic steroid therapy in excess of replacement doses or on any other form of immunosuppressive medication * Has a history of a previous additional malignancy unless potentially curative treatment has been completed with no evidence of malignancy for 5 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has an active autoimmune disease * Has an active infection requiring systemic treatment * Has interstitial lung disease * Has active or past history of (non-infectious) pneumonitis requiring steroids * Has symptomatic ascites or pleural effusion * Has previously had a hematopoetic stem cell transplant or solid organ transplant * Is known to be human immunodeficiency virus (HIV) positive and/or known to have active chronic or acute Hepatitis B or Hepatitis C * Has a known psychiatric and/or substance abuse disorder that would make it difficult for the participant to cooperate with the requirements of the trial * Is a regular user (including recreational use) of any illicit drugs at the time of providing documented informed consent, or has a recent history (within the last year) of substance abuse * Has received a live virus vaccine within 30 days prior to the first dose of study treatment * Has had hormonal cancer therapy (e.g., tamoxifen, leuprolide). within 4 weeks prior to the first dose of study treatment * For Part A participants with NSCLC added with Amendment 7: Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) other than an aspirin dose ≤1.3 gram per day for a 5-day period (8-day period for long-acting agents, such as piroxicam) * For Part A participants with NSCLC added with Amendment 7: Is unable or unwilling to take folic acid or Vitamin B12 supplementation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months | Up to 24 Months | A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE4.0). |
| Number of Participants Who Experienced At Least One Adverse Event (AE) | Up to 28 Months | An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to 24 Months | An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR in Participants With Extensive-stage Small Cell Lung Cancer (ES-SCLC) Per RECIST 1.1 | Up to 24 Months | ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Participants with ES-SCLC treated with vibostolimab in combination with pembrolizumab, carboplatin or cisplatin, and etoposide were analyzed. |
| ORR in Participants With PD-1 Naive Ovarian Cancer Per RECIST 1.1 | Up to 24 Months | ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Participants with PD-1 naive ovarian cancer treated with pembrolizumab and vibostolimab dose escalation or MK-7984A were analyzed. |
| ORR in Participants With PD-1 Naive Cervical Cancer Per RECIST 1.1 | Up to 24 Months | ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Results for participants with PD-1 naive cervical cancer treated with pembrolizumab and either 200 mg or 700 mg vibostolimab are presented. |
| Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5, and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22. | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the AUC 0-21 days of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab monotherapy or vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. Due to terminal fitting issue, non-calculable AUC0-21 days was replaced with AUClast for a few participants. |
| AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab in order to determine the AUC 0-21 days of plasma vibostolimab, Due to terminal fitting issue, non-calculable AUC0-21 days was replaced with AUClast for a few participants. |
| AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the AUC 0-21 days of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. Due to terminal fitting issue, non-calculable AUC0-21 days was replaced with AUClast for a few participants. |
| AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab and 200 mg pembrolizumab in order to determine the AUC 0-21 days of plasma pembrolizumab. Due to terminal fitting issue, non-calculable AUC0-21 days was replaced with AUClast for a few participants. |
| Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the Cmax of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab monotherapy or vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. |
| Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab in order to determine the Cmax of plasma vibostolimab, |
| Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the Cmax of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. |
| Overall Response Rate (ORR) in Participants in Vibostolimab Dose Escalation Phase Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Up to 24 Months | ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Results for participants treated with vibostolimab dose escalation are presented. |
| Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the Ctrough of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab monotherapy or vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. |
| Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab in order to determine the Ctrough of plasma vibostolimab, |
| Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the Ctrough of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. |
| Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab and 200 mg pembrolizumab in order to determine the Ctrough of plasma pembrolizumab. |
| Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the t1/2 of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab monotherapy or vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. |
| t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab in order to determine thet1/2 of plasma vibostolimab, |
| t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the t1/2 of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. |
| t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab and 200 mg pembrolizumab in order to determine the t1/2 of plasma pembrolizumab. |
| Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1 | At the end of Cycle 1 (up to 21 days) | A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by CTCAE 4.0 |
| Rate of Progression Free Survival (PFS) Per RECIST 1.1 at 6 Months | 6 months | The progression free survival (PFS) rate is the percentage of participants who achieve PFS as estimated by the Kaplan-Meier method. PFS is the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first using RECIST, version 1.1 as assessed by investigator review. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Rate of PFS was planned and therefore only reported for participants treated with vibostolimab in combination with pembrolizumab, carboplatin or cisplatin, and etoposide. Other treatment groups were not analyzed. |
| Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22 | Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab and 200 mg pembrolizumab in order to determine the Cmax of plasma pembrolizumab. |
| ORR in Participants With Programmed Death 1 (PD-1) Refractory Non-small Cell Lung Cancer (NSCLC) Per RECIST 1.1 | Up to 24 Months | ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Results for participants with PD-1 refractory NSCLC treated with 200 or 210 mg vibostolimab in dose escalation as well as dose expansion phases are presented. |
| ORR in Participants With PD-1 Naive NSCLC Per RECIST 1.1 | Up to 24 Months | ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Results for participants with PD-1 naive NSCLC treated with pembrolizumab and 200 mg vibostolimab from both the dose escalation and expansion phases are presented. |
Participant flow
Recruitment details
Participants at least 18 years of age with advanced solid tumors were enrolled in this study.
Pre-assignment details
As it was pre-specified to assign treatment groups irrespective of dose level, or cohorts such as based on type of cancer or country of origin, participants were instead combined into treatment groups based on their unique combination of interventions. For dose escalation, it was pre-specifed that participants were combined into monotherapy or sequential treatment groups rather than separate dose levels. Parts A and B were conducted at the same time, not sequentially.
Participants by arm
| Arm | Count |
|---|---|
| Vibostolimab During an initial dose evaluation phase, participants received various doses of vibostolimab on Day 1 of each 21-day infusion cycle (for a maximum of 35 cycles) until the recommended Phase 2 dose (RPTD) of 200 mg was established based on the number of dose limiting toxicities (DLTs) at each dose level. Participants continued receiving 200 mg vibostolimab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached. | 68 |
| Vibostolimab + Pembrolizumab During an initial dose evaluation phase, participants received various doses of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle (for a maximum of 35 cycles) until the RPTD of vibostolimab of 200 mg was established based on the number of DLTs at each dose level. Participants continued receiving 200 mg of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit was reached. | 293 |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) Participants received a fixed dose of pembrolizumab/vibostolimab coformulation, consisting of 200 mg of pembrolizumab + 200 mg vibostolimab, on Day 1 of each 21-day infusion cycle for up to 35 cycles. | 60 |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin Participants received a 200 mg dose of vibostolimab in combination with 200 mg pembrolizumab, 500 mg/m\^2 pemetrexed, and Area Under Curve (AUC) 5 mg/mL/min carboplatin on Day 1 of each 21-day infusion cycle for up to 4 cycles followed by maintenance therapy with a 200 mg dose of vibostolimab in combination with 200 mg pembrolizumab and 500 mg/m\^2 pemetrexed on Day 1 of each 21-day infusion cycle for up to an additional 31 cycles. | 10 |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide Participants received 200 mg vibostolimab in combination with 200 mg pembrolizumab, plus the investigator's choice of Area Under Curve (AUC) 5 mg/mL/min carboplatin OR 75 mg/m\^2 cisplatin on Day 1 of each 21-day cycle plus 100 mg/m\^2/day etoposide on Days 1-3 of each 21-day cycle for up to 4 cycles. Maintenance therapy with 200 mg vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day cycle will continue for up to an additional 31 cycles. A participant will be allowed to switch from cisplatin to carboplatin in the event of an adverse event (AE), ineligibility for further cisplatin therapy, and/or the investigator considers switching to carboplatin to be in the best interest of the participant. | 40 |
| Total | 471 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 58 | 239 | 38 | 10 | 33 |
| Overall Study | Lost to Follow-up | 1 | 4 | 2 | 0 | 0 |
| Overall Study | Not Treated | 0 | 2 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Sponsor Decision | 3 | 22 | 11 | 0 | 7 |
| Overall Study | Withdrawal by Subject | 6 | 27 | 9 | 0 | 0 |
Baseline characteristics
| Characteristic | Vibostolimab | Vibostolimab + Pembrolizumab | Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 63.1 Years STANDARD_DEVIATION 12 | 57.6 Years STANDARD_DEVIATION 12 | 58.5 Years STANDARD_DEVIATION 10 | 68.5 Years STANDARD_DEVIATION 9 | 66.2 Years STANDARD_DEVIATION 8.2 | 59.3 Years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 17 Participants | 1 Participants | 0 Participants | 2 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 268 Participants | 57 Participants | 9 Participants | 37 Participants | 430 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 8 Participants | 2 Participants | 1 Participants | 1 Participants | 14 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 | 13 Participants | 99 Participants | 25 Participants | 5 Participants | 27 Participants | 169 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 8 Participants | 1 Participants | 0 Participants | 0 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) White | 48 Participants | 181 Participants | 34 Participants | 5 Participants | 12 Participants | 280 Participants |
| Sex: Female, Male Female | 34 Participants | 190 Participants | 43 Participants | 5 Participants | 10 Participants | 282 Participants |
| Sex: Female, Male Male | 34 Participants | 103 Participants | 17 Participants | 5 Participants | 30 Participants | 189 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 | 60 / 68 | 243 / 295 | 22 / 25 | 39 / 60 | 11 / 11 | 33 / 40 |
| other Total, other adverse events | 64 / 68 | 274 / 293 | 23 / 25 | 60 / 60 | 10 / 10 | 40 / 40 |
| serious Total, serious adverse events | 18 / 68 | 99 / 293 | 7 / 25 | 26 / 60 | 5 / 10 | 13 / 40 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Time frame: Up to 24 Months
Population: The population analyzed was treated participants. Per protocol, participants were assigned to a treatment group based on their unique combination of interventions. Hence for dose escalation, participants were assigned. to either monotherapy or sequential treatment groups rather than by dosage levels.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vibostolimab | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| Vibostolimab + Pembrolizumab | Number of Participants Who Discontinued Study Treatment Due to an AE | 30 Participants |
| Vibostolimab + Pembrolizumab After Crossover | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Number of Participants Who Discontinued Study Treatment Due to an AE | 4 Participants |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Number of Participants Who Discontinued Study Treatment Due to an AE | 3 Participants |
Primary
Number of Participants Who Experienced At Least One Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.
Time frame: Up to 28 Months
Population: The population analyzed was treated participants. Per protocol, participants were assigned to a treatment group based on their unique combination of interventions. Hence for dose escalation, participants were assigned. to either monotherapy or sequential treatment groups rather than by dosage levels.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vibostolimab | Number of Participants Who Experienced At Least One Adverse Event (AE) | 67 Participants |
| Vibostolimab + Pembrolizumab | Number of Participants Who Experienced At Least One Adverse Event (AE) | 284 Participants |
| Vibostolimab + Pembrolizumab After Crossover | Number of Participants Who Experienced At Least One Adverse Event (AE) | 24 Participants |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Number of Participants Who Experienced At Least One Adverse Event (AE) | 60 Participants |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Number of Participants Who Experienced At Least One Adverse Event (AE) | 10 Participants |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Number of Participants Who Experienced At Least One Adverse Event (AE) | 40 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE4.0).
Time frame: Up to 24 Months
Population: The population analyzed was treated participants. Per protocol, participants were assigned to a treatment group based on their unique combination of interventions. Hence for dose escalation, participants were assigned. to either monotherapy or sequential treatment groups rather than by dosage levels.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vibostolimab | Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months | 0 Participants |
| Vibostolimab + Pembrolizumab | Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months | 0 Participants |
| Vibostolimab + Pembrolizumab After Crossover | Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months | 0 Participants |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months | 0 Participants |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months | 1 Participants |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months | 0 Participants |
Secondary
Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the AUC 0-21 days of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab monotherapy or vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. Due to terminal fitting issue, non-calculable AUC0-21 days was replaced with AUClast for a few participants.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5, and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22.
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Only participants with dose escalation were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 5.42 day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 12.2 day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | 12.4 day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 38.3 day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | NA day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 97.7 day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 339 day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 572 day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 1220 day*μg/mL |
| Vibostolimab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 1090 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 519 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 8.19 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 156 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 12.0 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 2080 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 354 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 28.5 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 1250 day*μg/mL |
| Vibostolimab + Pembrolizumab | Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | 48.3 day*μg/mL |
Secondary
AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab and 200 mg pembrolizumab in order to determine the AUC 0-21 days of plasma pembrolizumab. Due to terminal fitting issue, non-calculable AUC0-21 days was replaced with AUClast for a few participants.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Cycle 4 for participants treated with etoposide was not analyzed due to insufficient time points available to determine AUC0-21 days.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 516 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 887 day*μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 546 day*μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 946 day*μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 974 day*μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 539 day*μg/mL |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 641 day*μg/mL |
Secondary
AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the AUC 0-21 days of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed. Due to terminal fitting issue, non-calculable AUC0-21 days was replaced with AUClast for a few participants.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Only participants with pembrolizumab and dose escalation were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 760 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 749 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 516 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | 922 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 504 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 516 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 887 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 541 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 1050 day*μg/mL |
Secondary
AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab in order to determine the AUC 0-21 days of plasma vibostolimab, Due to terminal fitting issue, non-calculable AUC0-21 days was replaced with AUClast for a few participants.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Cycle 4 for participants treated with etoposide was not analyzed due to insufficient time points available to determine AUC0-21 days.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 572 day*μg/mL |
| Vibostolimab | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 339 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 519 day*μg/mL |
| Vibostolimab + Pembrolizumab | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 354 day*μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 431 day*μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 655 day*μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 342 day*μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 317 day*μg/mL |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 476 day*μg/mL |
Secondary
Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab and 200 mg pembrolizumab in order to determine the Cmax of plasma pembrolizumab.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Cycle 4 for participants treated with etoposide was not analyzed due to insufficient time points available to determine Cmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 76.1 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 93.9 μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 66.4 μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 73.2 μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 91.1 μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 71.6 μg/mL |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 64.4 μg/mL |
Secondary
Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the Cmax of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Only participants with pembrolizumab and dose escalation were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 89.3 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 86.4 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 58.4 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | 95.0 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 90.5 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 76.1 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 93.9 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 81.6 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 103 μg/mL |
Secondary
Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab in order to determine the Cmax of plasma vibostolimab,
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Cycle 4 for participants treated with etoposide was not analyzed due to insufficient time points available to determine Cmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 62.6 μg/mL |
| Vibostolimab | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 82.7 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 80.1 μg/mL |
| Vibostolimab + Pembrolizumab | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 64.4 μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 56.4 μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 59.9 μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 57.8 μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 60.1 μg/mL |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 59.6 μg/mL |
Secondary
Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab and 200 mg pembrolizumab in order to determine the Ctrough of plasma pembrolizumab.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Cycle 4 for participants treated with etoposide was not analyzed due to insufficient time points available to determine Ctrough.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 12.1 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 23.3 μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 13.2 μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 24.7 μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 31.0 μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 12.5 μg/mL |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 10.9 μg/mL |
Secondary
Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the Ctrough of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Only participants with pembrolizumab and dose escalation were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 19.8 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 20.6 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 10.4 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | 28.0 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 12.3 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 12.1 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 23.3 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 11.1 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 25.7 μg/mL |
Secondary
Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab in order to determine the Ctrough of plasma vibostolimab,
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Cycle 4 for participants treated with etoposide was not analyzed due to insufficient time points available to determine Ctrough.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 10.7 μg/mL |
| Vibostolimab | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 3.82 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 9.66 μg/mL |
| Vibostolimab + Pembrolizumab | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 5.05 μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 8.01 μg/mL |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 15.5 μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 9.01 μg/mL |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 2.50 μg/mL |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 4.16 μg/mL |
Secondary
Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the t1/2 of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab monotherapy or vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Only participants with dose escalation were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 3.82 Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 4.04 Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | 3.54 Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 7.19 Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | NA Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 5.45 Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 7.58 Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 11.6 Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 6.04 Days |
| Vibostolimab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 8.39 Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 10.5 Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | NA Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 6.55 Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | NA Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 10.7 Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 7.38 Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 7.11 Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 8.42 Days |
| Vibostolimab + Pembrolizumab | Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | 11.0 Days |
Secondary
Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the Cmax of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab monotherapy or vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Only participants with dose escalation were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 1.52 μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 7.23 μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | 7.57 μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 8.64 μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | NA μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 19.5 μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 62.6 μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 82.7 μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 202 μg/mL |
| Vibostolimab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 215 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 80.1 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 1.67 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 24.9 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 2.09 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 245 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 64.4 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 4.70 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 236 μg/mL |
| Vibostolimab + Pembrolizumab | Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | 6.30 μg/mL |
Secondary
Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by CTCAE 4.0
Time frame: At the end of Cycle 1 (up to 21 days)
Population: The population analyzed was treated participants. Per protocol, participants were assigned to a treatment group based on their unique combination of interventions. Hence for dose escalation, participants were assigned. to either monotherapy or sequential treatment groups rather than by dosage levels.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vibostolimab | Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1 | 0 Participants |
| Vibostolimab + Pembrolizumab | Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1 | 0 Participants |
| Vibostolimab + Pembrolizumab After Crossover | Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1 | 0 Participants |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1 | 0 Participants |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1 | 1 Participants |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1 | 0 Participants |
Secondary
ORR in Participants With Extensive-stage Small Cell Lung Cancer (ES-SCLC) Per RECIST 1.1
ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Participants with ES-SCLC treated with vibostolimab in combination with pembrolizumab, carboplatin or cisplatin, and etoposide were analyzed.
Time frame: Up to 24 Months
Population: Participants with a baseline scan with measurable disease by investigator assessment who were administered a dose of study treatment regardless of dose level. For ES-SCLC only participants in the etoposide treatment group were analyzed, based on their combination of interventions rather than by dosage levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | ORR in Participants With Extensive-stage Small Cell Lung Cancer (ES-SCLC) Per RECIST 1.1 | 75.0 Percentage of participants |
Secondary
ORR in Participants With PD-1 Naive Cervical Cancer Per RECIST 1.1
ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Results for participants with PD-1 naive cervical cancer treated with pembrolizumab and either 200 mg or 700 mg vibostolimab are presented.
Time frame: Up to 24 Months
Population: Participants with a baseline scan with measurable disease by investigator assessment who were administered a dose of study treatment regardless of dose level. For PD-1 naive cervical cancer only participants treated with vibostolimab and pembrolizumab sequentially were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | ORR in Participants With PD-1 Naive Cervical Cancer Per RECIST 1.1 | Vibostolimab 200 mg | 14.6 Percentage of participants |
| Vibostolimab + Pembrolizumab | ORR in Participants With PD-1 Naive Cervical Cancer Per RECIST 1.1 | Vibostolimab 700 mg | 23.1 Percentage of participants |
Secondary
ORR in Participants With PD-1 Naive NSCLC Per RECIST 1.1
ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Results for participants with PD-1 naive NSCLC treated with pembrolizumab and 200 mg vibostolimab from both the dose escalation and expansion phases are presented.
Time frame: Up to 24 Months
Population: Participants with a baseline scan with measurable disease by investigator assessment who were administered a dose of study treatment regardless of dose level. Both dose escalation and expansion phases were analyzed assigned to treatment groups based on their combination of interventions rather than by dosage levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vibostolimab + Pembrolizumab | ORR in Participants With PD-1 Naive NSCLC Per RECIST 1.1 | 24.4 Percentage of participants |
Secondary
ORR in Participants With PD-1 Naive Ovarian Cancer Per RECIST 1.1
ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Participants with PD-1 naive ovarian cancer treated with pembrolizumab and vibostolimab dose escalation or MK-7984A were analyzed.
Time frame: Up to 24 Months
Population: Participants with a baseline scan with measurable disease by investigator assessment who were administered a dose of study treatment regardless of dose level. For PD-1 naive ovarian cancer only participants treated with vibostolimab and pembrolizumab taken sequentially, or as a coformulation were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vibostolimab + Pembrolizumab | ORR in Participants With PD-1 Naive Ovarian Cancer Per RECIST 1.1 | 9.5 Percentage of participants |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | ORR in Participants With PD-1 Naive Ovarian Cancer Per RECIST 1.1 | 7.5 Percentage of participants |
Secondary
ORR in Participants With Programmed Death 1 (PD-1) Refractory Non-small Cell Lung Cancer (NSCLC) Per RECIST 1.1
ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Results for participants with PD-1 refractory NSCLC treated with 200 or 210 mg vibostolimab in dose escalation as well as dose expansion phases are presented.
Time frame: Up to 24 Months
Population: Participants with a baseline scan with measurable disease by investigator assessment who were administered a dose of study treatment regardless of dose level. Both dose escalation and expansion phases were analyzed, assigned to treatment groups based on their combination of interventions rather than by dosage levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vibostolimab | ORR in Participants With Programmed Death 1 (PD-1) Refractory Non-small Cell Lung Cancer (NSCLC) Per RECIST 1.1 | 2.4 Percentage of participants |
| Vibostolimab + Pembrolizumab | ORR in Participants With Programmed Death 1 (PD-1) Refractory Non-small Cell Lung Cancer (NSCLC) Per RECIST 1.1 | 5.3 Percentage of participants |
Secondary
Overall Response Rate (ORR) in Participants in Vibostolimab Dose Escalation Phase Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
ORR is the percentage of participants who experience 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) at any time during the trial using RECIST, version 1.1 as assessed by investigator review. Results for participants treated with vibostolimab dose escalation are presented.
Time frame: Up to 24 Months
Population: Participants with a baseline scan with measurable disease by investigator assessment who were administered a dose of study treatment regardless of dose level. Only dose escalation treatment groups were analyzed, who were assigned based on their combination of interventions rather than by dosage levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vibostolimab | Overall Response Rate (ORR) in Participants in Vibostolimab Dose Escalation Phase Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 0.0 Percentage of participants |
| Vibostolimab + Pembrolizumab | Overall Response Rate (ORR) in Participants in Vibostolimab Dose Escalation Phase Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 7.1 Percentage of participants |
Secondary
Rate of Progression Free Survival (PFS) Per RECIST 1.1 at 6 Months
The progression free survival (PFS) rate is the percentage of participants who achieve PFS as estimated by the Kaplan-Meier method. PFS is the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first using RECIST, version 1.1 as assessed by investigator review. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Rate of PFS was planned and therefore only reported for participants treated with vibostolimab in combination with pembrolizumab, carboplatin or cisplatin, and etoposide. Other treatment groups were not analyzed.
Time frame: 6 months
Population: Participants with a baseline scan with measurable disease by investigator assessment who were administered a dose of study treatment regardless of dose level. Only participants treated with vibostolimab in combination with pembrolizumab, carboplatin or cisplatin, and etoposide were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | Rate of Progression Free Survival (PFS) Per RECIST 1.1 at 6 Months | 35.0 Percentage of participants |
Secondary
t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab and 200 mg pembrolizumab in order to determine the t1/2 of plasma pembrolizumab.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Cycle 4 for participants treated with etoposide was not analyzed due to insufficient time points available to determine t1/2.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 11.2 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 14.3 Days |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 12.4 Days |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | NA Days |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 4 | 17.7 Days |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | 16.6 Days |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments | Cycle 1 | NA Days |
Secondary
t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the t1/2 of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Only participants with pembrolizumab and dose escalation were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | 19.6 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | 20.1 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 8.84 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | 18.6 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 13.1 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 11.2 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 14.3 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 11.0 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 16.1 Days |
Secondary
t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) following treatment with 200 mg vibostolimab in order to determine thet1/2 of plasma vibostolimab,
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Cycle 4 for participants treated with etoposide was not analyzed due to insufficient time points available to determine t1/2.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 7.38 Days |
| Vibostolimab + Pembrolizumab | t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 10.5 Days |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 9.09 Days |
| Pembrolizumab/Vibostolimab Coformulation (MK-7684A) | t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | NA Days |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 4 | 10.5 Days |
| Vibostolimab +Pembrolizumab+Pemetrexed+Carboplatin | t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | 5.38 Days |
| Vibostolimab+Pembrolizumab+Carboplatin OR Cisplatin+Etoposide | t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments | 200 mg vibostolimab Cycle 1 | NA Days |
Secondary
Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab
Blood samples were collected from participants during cycle 1 and cycle 4 of treatment (Cycle length is 21 days) in order to determine the Ctrough of plasma vibostolimab, Only results from participants treated with increasing amounts of vibostolimab monotherapy or vibostolimab combined with 200 mg pembrolizumab are presented; whereas other treatment groups were not analyzed.
Time frame: Cycle 1, Cycle 4: Day 1 pre-dose, 0.5 and 2 hours post-dose; once daily on Days 2, 3, 5, 8, 15 and 22
Population: Participants who complied with the protocol sufficiently to ensure that the data they generated will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements, and absence of major protocol violations. Only participants with dose escalation were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | NA μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | NA μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 0.539 μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | NA μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 3.21 μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 3.82 μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 10.7 μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 10.0 μg/mL |
| Vibostolimab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 41.3 μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 4 | 9.66 μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 2.10 mg Cycle 1 | NA μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 70.0 mg Cycle 1 | 1.79 μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 1 | NA μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 4 | 40.1 μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 7.00 mg Cycle 4 | NA μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 200 mg Cycle 1 | 5.05 μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 1 | 0.397 μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 700 mg Cycle 1 | 19.3 μg/mL |
| Vibostolimab + Pembrolizumab | Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab | Vibostolimab 21.0 mg Cycle 4 | 1.11 μg/mL |