Select Advanced Solid Tumors
Conditions
Keywords
IMCnyeso, Immunotherapy
Brief summary
IMCnyeso is a bispecific fusion protein designed for the treatment of cancers that express NY-ESO-1 and/or LAGE-1A. This was a first-in-human trial designed to evaluate the safety and efficacy of IMCnyeso in HLA-A\*02:01-positive adult participants whose cancer is positive for NY-ESO-1 and/or LAGE-A1.
Detailed description
This was planned to be a multi-center, open label, dose finding Phase 1/2 study of single agent IMCnyeso administered in participants with NY-ESO-1 and/or LAGE-A1 positive tumors. The primary objective of the dose escalation phase (Phase 1) was to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of IMCnyeso in participants with advanced solid tumors. Preliminary efficacy was to be evaluated in Phase 2. The study was terminated early (prior to initiation of Phase 2) by the Sponsor as a strategic decision (not based on any safety signal).
Interventions
DRUGIMCnyeso
Weekly IV infusions of IMCnyeso
Sponsors
Immunocore Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. HLA-A\*0201 positive 2. NY-ESO-1 and/or LAGE-1A positive tumor 3. ECOG PS 0 or 1 4. Selected advanced solid tumors 5. Relapsed from, refractory to, or intolerant of standard therapy 6. If applicable, must agree to use highly effective contraception
Exclusion criteria
1. Symptomatic or untreated central nervous system metastasis 2. Inadequate washout from prior anticancer therapy 3. Significant ongoing toxicity from prior anticancer treatment 4. Impaired baseline organ function as evaluated by out-of-range laboratory values 5. Clinically significant cardiac disease 6. Active infection requiring systemic antibiotic therapy 7. Known history of human immunodeficiency virus (HIV) 8. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) 9. Ongoing treatment with systemic steroids or other immunosuppressive therapies 10. Significant secondary malignancy 11. Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Dose-limiting Toxicities | Up to 35 months | Dose-limiting toxicities were defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug that occurs within the evaluation period, from the first dose up until Day 28 after the first dose |
| Phase 1: Number of Participants With Adverse Events | Up to 35 months | Treatment-emergent adverse events are defined as any adverse event (AE) that started after the first dose of study drug up to 30 days after last dose of study drug, including abnormal laboratory values, vital signs, or electrocardiogram results. AE severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. |
| Phase 1: Number of Participants With No Dose Interruptions or Reductions | Up to 35 months | Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions |
| Phase 2: Best Overall Response (BOR) | Up to 35 months | Best overall response per RECIST v.1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and Phase 2: Duration of Response | Up to 35 months | Duration of response is defined as the time from the date of first documented objective response (CR or PR) until the date of documented disease progression or death. |
| Phase 1 and Phase 2: Overall Survival | Up to 35 months | Overall Survival is defined as the time (in months) from the date of randomization to the date of death due to any cause. |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15 | — |
| Phase 2: Number of Participants With Adverse Events | Up to 35 months | Treatment-emergent adverse events are defined as any adverse event (AE) that started after the first dose of study drug up to 30 days after last dose of study drug, including abnormal laboratory values, vital signs, or electrocardiogram results. |
| Time to Reach Maximum Plasma Concentration (Tmax) | Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15 | — |
| Number of Participants With Anti-IMCnyeso Antibody Formation | Up to 35 months | Number of participants with positive treatment-boosted or treatment-induced anti-IMCnyeso antibody titers |
| Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15 | — |
| Phase 2: Number of Participants With No Dose Interruptions or Reductions | Up to 35 months | Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions |
| Phase 1: Number of Participants With Best Overall Response (BOR) | Up to 35 months | Number of participants with best overall response, including complete response, partial response, stable disease, and progressive disease, based on local Investigator assessment as defined in RECIST v.1.1. |
| Phase 1 and Phase 2: Progression-free Survival | Up to 35 months | Progression-free survival is defined as the time from first dose until the date of objective progression, or death from any cause, whichever occurs first. |
Countries
Canada, United Kingdom, United States
Participant flow
Recruitment details
The sponsor elected to not proceed with the efficacy determining expansion phase (Phase 2) of IMCnyeso-101 for strategic reasons. Phase 2 data were not collected. As of 25 Mar 2021, further enrollment into the Phase 1 dose escalation phase was discontinued and last patient visit was 10 June 2021. Participants who were receiving study drug were allowed to continue treatment until unacceptable toxicity, disease progression, or other reason to discontinue occurred.
Pre-assignment details
There were a total of 28 unique participants; one participant from the 10 mcg cohort was sequentially enrolled in the 30-100 mcg cohort.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: IMCnyeso 3 mcg Single-agent IMCnyeso at 3 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen | 4 |
| Phase 1: IMCnyeso 10 mcg Single-agent IMCnyeso at 10 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen | 2 |
| Phase 1: IMCnyeso 30 mcg Single-agent IMCnyeso at 30 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen | 5 |
| Phase 1: IMCnyeso 100 mcg Single-agent IMCnyeso at 100 mcg dosed weekly intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using a fixed-dose regimen | 3 |
| Phase 1: IMCnyeso 30-100 mcg IMCnyeso administered intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using an intrapatient escalation regimen (30 mcg on Cycle 1 Day 1, then 100 mcg starting on Cycle 1 Day 8) | 5 |
| Phase 1: IMCnyeso 30-100-180 mcg IMCnyeso administered intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using an intrapatient escalation regimen (30 mcg on Cycle 1 Day 1, then 100 mcg on Cycle 1 Day 8, then 180 mcg starting on Cycle 1 Day 15) | 4 |
| Phase 1: IMCnyeso 30-100-300 mcg IMCnyeso administered intravenously on Days 1, 8, 15, and 22 of each 4-week cycle using an intrapatient escalation regimen (30 mcg on Cycle 1 Day 1, then 100 mcg on Cycle 1 Day 8, then 300 mcg starting on Cycle 1 Day 15) | 5 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 4 | 1 | 2 | 2 | 2 | 4 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Sequential enrollment in 30-100 mcg cohort | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study ended by sponsor | 0 | 0 | 2 | 1 | 3 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Phase 1: IMCnyeso 3 mcg | Phase 1: IMCnyeso 10 mcg | Phase 1: IMCnyeso 30 mcg | Phase 1: IMCnyeso 100 mcg | Phase 1: IMCnyeso 30-100 mcg | Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: IMCnyeso 30-100-300 mcg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-64 years old | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 23 Participants |
| Age, Customized 65-84 years old | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 3 Participants | 3 Participants | 5 Participants | 3 Participants | 5 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Original cancer diagnosis Melanoma | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 7 Participants |
| Original cancer diagnosis Non-small cell lung cancer | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Original cancer diagnosis Synovial sarcoma | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 20 Participants |
| Original cancer diagnosis Urothelial carcinoma | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 2 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 1 / 3 | 2 / 5 | 2 / 3 | 2 / 5 | 4 / 4 | 1 / 5 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 5 / 5 | 3 / 3 | 5 / 5 | 4 / 4 | 5 / 5 |
| serious Total, serious adverse events | 3 / 4 | 1 / 3 | 1 / 5 | 1 / 3 | 2 / 5 | 3 / 4 | 3 / 5 |
Outcome results
Primary
Phase 1: Number of Participants With Adverse Events
Treatment-emergent adverse events are defined as any adverse event (AE) that started after the first dose of study drug up to 30 days after last dose of study drug, including abnormal laboratory values, vital signs, or electrocardiogram results. AE severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Time frame: Up to 35 months
Population: The Safety Analysis Set includes all participants who received at least 1 full or partial dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE leading to death | 0 Participants |
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE Grade ≥3 | 3 Participants |
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Adverse Events | Any treatment-emergent adverse event (TEAE) | 4 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE Grade ≥3 | 1 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Adverse Events | Any treatment-emergent adverse event (TEAE) | 3 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE leading to death | 0 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE leading to death | 0 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Adverse Events | Any treatment-emergent adverse event (TEAE) | 5 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE Grade ≥3 | 1 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE Grade ≥3 | 3 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Adverse Events | Any treatment-emergent adverse event (TEAE) | 3 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE leading to death | 0 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE Grade ≥3 | 3 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Adverse Events | Any treatment-emergent adverse event (TEAE) | 5 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE leading to death | 0 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Adverse Events | Any treatment-emergent adverse event (TEAE) | 4 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE leading to death | 0 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE Grade ≥3 | 4 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE leading to death | 0 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Adverse Events | Any TEAE Grade ≥3 | 4 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Adverse Events | Any treatment-emergent adverse event (TEAE) | 5 Participants |
Primary
Phase 1: Number of Participants With Dose-limiting Toxicities
Dose-limiting toxicities were defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug that occurs within the evaluation period, from the first dose up until Day 28 after the first dose
Time frame: Up to 35 months
Population: The Safety Analysis Set includes all participants who received at least 1 full or partial dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Dose-limiting Toxicities | 0 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Dose-limiting Toxicities | 0 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Dose-limiting Toxicities | 0 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Dose-limiting Toxicities | 0 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Dose-limiting Toxicities | 0 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Dose-limiting Toxicities | 0 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Dose-limiting Toxicities | 2 Participants |
Primary
Phase 1: Number of Participants With No Dose Interruptions or Reductions
Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions
Time frame: Up to 35 months
Population: The Safety Analysis Set includes all participants who received at least 1 full or partial dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose interruption at any time | 2 Participants |
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose reduction at any time | 4 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose interruption at any time | 0 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose reduction at any time | 3 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose interruption at any time | 0 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose reduction at any time | 5 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose interruption at any time | 2 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose reduction at any time | 3 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose interruption at any time | 2 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose reduction at any time | 4 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose interruption at any time | 0 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose reduction at any time | 4 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose interruption at any time | 0 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With No Dose Interruptions or Reductions | No dose reduction at any time | 3 Participants |
Primary
Phase 2: Best Overall Response (BOR)
Best overall response per RECIST v.1.1
Time frame: Up to 35 months
Population: The study was terminated during Phase 1 due to strategic reasons; data were not collected or analyzed for any Phase 2 outcome measures.
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last)
Time frame: Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
Population: The pharmacokinetic analysis set includes participants in the safety analysis set with at least 1 post-dose sample providing evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 1 | 12500 hr*pg/mL | Standard Deviation 6910 |
| Phase 1: IMCnyeso 3 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 15 | 7270 hr*pg/mL | Standard Deviation 4530 |
| Phase 1: IMCnyeso 10 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 1 | 17700 hr*pg/mL | Standard Deviation 14400 |
| Phase 1: IMCnyeso 10 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 15 | 29500 hr*pg/mL | Standard Deviation 35900 |
| Phase 1: IMCnyeso 30 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 1 | 132000 hr*pg/mL | Standard Deviation 44600 |
| Phase 1: IMCnyeso 30 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 15 | 149000 hr*pg/mL | Standard Deviation 70500 |
| Phase 1: IMCnyeso 100 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 1 | 295000 hr*pg/mL | Standard Deviation 72400 |
| Phase 1: IMCnyeso 100 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 15 | 301000 hr*pg/mL | Standard Deviation 223000 |
| Phase 1: IMCnyeso 30-100 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 1 | 182000 hr*pg/mL | Standard Deviation 180000 |
| Phase 1: IMCnyeso 30-100 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 15 | 497000 hr*pg/mL | Standard Deviation 260000 |
| Phase 1: IMCnyeso 30-100-180 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 1 | 78800 hr*pg/mL | Standard Deviation 32500 |
| Phase 1: IMCnyeso 30-100-180 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 15 | 611000 hr*pg/mL | Standard Deviation 330000 |
| Phase 1: IMCnyeso 30-100-300 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 1 | 127000 hr*pg/mL | Standard Deviation 53700 |
| Phase 1: IMCnyeso 30-100-300 mcg | Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last) | Cycle 1 Day 15 | 142000 hr*pg/mL | — |
Secondary
Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax)
Time frame: Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
Population: The pharmacokinetic analysis set includes participants in the safety analysis set with at least 1 post-dose sample providing evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 1 | 1130 pg/mL | Standard Deviation 674 |
| Phase 1: IMCnyeso 3 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 15 | 1090 pg/mL | Standard Deviation 634 |
| Phase 1: IMCnyeso 10 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 1 | 1530 pg/mL | Standard Deviation 1160 |
| Phase 1: IMCnyeso 10 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 15 | 1800 pg/mL | Standard Deviation 1290 |
| Phase 1: IMCnyeso 30 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 15 | 6220 pg/mL | Standard Deviation 1450 |
| Phase 1: IMCnyeso 30 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 1 | 6850 pg/mL | Standard Deviation 1110 |
| Phase 1: IMCnyeso 100 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 15 | 17900 pg/mL | Standard Deviation 1910 |
| Phase 1: IMCnyeso 100 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 1 | 16100 pg/mL | Standard Deviation 961 |
| Phase 1: IMCnyeso 30-100 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 15 | 19900 pg/mL | Standard Deviation 3570 |
| Phase 1: IMCnyeso 30-100 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 1 | 6810 pg/mL | Standard Deviation 5290 |
| Phase 1: IMCnyeso 30-100-180 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 1 | 3890 pg/mL | Standard Deviation 932 |
| Phase 1: IMCnyeso 30-100-180 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 15 | 26900 pg/mL | Standard Deviation 3930 |
| Phase 1: IMCnyeso 30-100-300 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 1 | 6710 pg/mL | Standard Deviation 1380 |
| Phase 1: IMCnyeso 30-100-300 mcg | Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax) | Cycle 1 Day 15 | 65800 pg/mL | — |
Secondary
Number of Participants With Anti-IMCnyeso Antibody Formation
Number of participants with positive treatment-boosted or treatment-induced anti-IMCnyeso antibody titers
Time frame: Up to 35 months
Population: The pharmacokinetic analysis set includes participants in the safety analysis set with at least 1 post-dose sample providing evaluable data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Number of Participants With Anti-IMCnyeso Antibody Formation | 0 Participants |
| Phase 1: IMCnyeso 10 mcg | Number of Participants With Anti-IMCnyeso Antibody Formation | 0 Participants |
| Phase 1: IMCnyeso 30 mcg | Number of Participants With Anti-IMCnyeso Antibody Formation | 0 Participants |
| Phase 1: IMCnyeso 100 mcg | Number of Participants With Anti-IMCnyeso Antibody Formation | 1 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Number of Participants With Anti-IMCnyeso Antibody Formation | 0 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Number of Participants With Anti-IMCnyeso Antibody Formation | 0 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Number of Participants With Anti-IMCnyeso Antibody Formation | 1 Participants |
Secondary
Phase 1 and Phase 2: Duration of Response
Duration of response is defined as the time from the date of first documented objective response (CR or PR) until the date of documented disease progression or death.
Time frame: Up to 35 months
Population: The study was terminated during Phase 1 due to strategic reasons; analysis of duration of response was not able to be performed in Phase 1 because no complete or partial responses were observed and no data were collected for Phase 2.
Secondary
Phase 1 and Phase 2: Overall Survival
Overall Survival is defined as the time (in months) from the date of randomization to the date of death due to any cause.
Time frame: Up to 35 months
Population: The study was terminated during Phase 1 due to strategic reasons; data were not collected or analyzed for this outcome measure in Phase 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Phase 1 and Phase 2: Overall Survival | 3.3 Months |
| Phase 1: IMCnyeso 10 mcg | Phase 1 and Phase 2: Overall Survival | NA Months |
| Phase 1: IMCnyeso 30 mcg | Phase 1 and Phase 2: Overall Survival | NA Months |
| Phase 1: IMCnyeso 100 mcg | Phase 1 and Phase 2: Overall Survival | 9.7 Months |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1 and Phase 2: Overall Survival | NA Months |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1 and Phase 2: Overall Survival | 7.5 Months |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1 and Phase 2: Overall Survival | NA Months |
Secondary
Phase 1 and Phase 2: Progression-free Survival
Progression-free survival is defined as the time from first dose until the date of objective progression, or death from any cause, whichever occurs first.
Time frame: Up to 35 months
Population: The study was terminated during Phase 1 due to strategic reasons; data were not collected or analyzed for this outcome measure in Phase 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Phase 1 and Phase 2: Progression-free Survival | 1.8 Months |
| Phase 1: IMCnyeso 10 mcg | Phase 1 and Phase 2: Progression-free Survival | 1.6 Months |
| Phase 1: IMCnyeso 30 mcg | Phase 1 and Phase 2: Progression-free Survival | 2.1 Months |
| Phase 1: IMCnyeso 100 mcg | Phase 1 and Phase 2: Progression-free Survival | 1.9 Months |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1 and Phase 2: Progression-free Survival | 2.1 Months |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1 and Phase 2: Progression-free Survival | 1.8 Months |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1 and Phase 2: Progression-free Survival | 1.4 Months |
Secondary
Phase 1: Number of Participants With Best Overall Response (BOR)
Number of participants with best overall response, including complete response, partial response, stable disease, and progressive disease, based on local Investigator assessment as defined in RECIST v.1.1.
Time frame: Up to 35 months
Population: The Full Analysis Set includes all participants assigned to treatment who receive at least 1 full or partial dose of study drug and for which evaluation was able to be made for at least 1 post-baseline tumor assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Non-evaluable | 1 Participants |
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| Phase 1: IMCnyeso 3 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Non-evaluable | 0 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Phase 1: IMCnyeso 10 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Non-evaluable | 0 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Stable Disease | 2 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| Phase 1: IMCnyeso 30 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| Phase 1: IMCnyeso 100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Non-evaluable | 0 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Non-evaluable | 0 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Stable Disease | 2 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| Phase 1: IMCnyeso 30-100 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Non-evaluable | 1 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Phase 1: IMCnyeso 30-100-180 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Stable Disease | 0 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Progressive Disease | 3 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Partial Response | 0 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Complete Response | 0 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Stable Disease | 1 Participants |
| Phase 1: IMCnyeso 30-100-300 mcg | Phase 1: Number of Participants With Best Overall Response (BOR) | Non-evaluable | 1 Participants |
Secondary
Phase 2: Number of Participants With Adverse Events
Treatment-emergent adverse events are defined as any adverse event (AE) that started after the first dose of study drug up to 30 days after last dose of study drug, including abnormal laboratory values, vital signs, or electrocardiogram results.
Time frame: Up to 35 months
Population: The study was terminated during Phase 1 due to strategic reasons; data were not collected or analyzed for any Phase 2 outcome measures.
Secondary
Phase 2: Number of Participants With No Dose Interruptions or Reductions
Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions
Time frame: Up to 35 months
Population: The study was terminated during Phase 1 due to strategic reasons; data were not collected or analyzed for any Phase 2 outcome measures
Secondary
Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15
Population: The pharmacokinetic analysis set includes participants in the safety analysis set with at least 1 post-dose sample providing evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: IMCnyeso 3 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 1 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 3 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 15 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 10 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 1 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 10 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 15 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 30 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 1 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 30 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 15 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 100 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 1 | 1.67 Hours | Standard Deviation 1.15 |
| Phase 1: IMCnyeso 100 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 15 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 30-100 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 1 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 30-100 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 15 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 30-100-180 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 1 | 1.25 Hours | Standard Deviation 0.5 |
| Phase 1: IMCnyeso 30-100-180 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 15 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 30-100-300 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 1 | 1.00 Hours | Standard Deviation 0 |
| Phase 1: IMCnyeso 30-100-300 mcg | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 15 | 2.00 Hours | — |