Uveal Melanoma
Conditions
Keywords
Tebentafusp, IMCgp100, gp100, metastatic melanoma, ImmTAC, Immunotherapy, Bispecific T cell receptor fusion protein, Immune mobilizing monoclonal T cell receptor, against cancer, UM, mUM, Kimmtrak
Brief summary
IMCgp100-102 is a Phase I/II study of the weekly intra-patient escalation dose regimen with IMCgp100 as a single agent in participants with metastatic uveal melanoma (mUM). According to this regimen, all participants in the trial received 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation commenced at the third weekly dose at C1D15. The Phase I testing of the intra-patient escalation dosing regimen is designed to achieve a higher exposure and maximal plasma concentration of IMCgp100 after doses at Cycle 1 Day 15 (C1D15) and thereafter.
Detailed description
This is a Phase I/II clinical study of IMCgp100 in participants with advanced uveal melanoma. This is a Phase I/II study of IMCgp100 administered on a weekly basis with an intra-patient escalation dosing regimen. The intra-patient escalation occurred at the third weekly dose on Cycle 1 Day 15 (C1D15). According to this regimen, all participants in the trial received 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW), and then a dose escalation commenced at the third weekly dose at C1D15 with the goal to achieve a long-term dosing regimen at a dose higher than that identified for the weekly dosing regimen (RP2D-QW). The dose escalation identified the intra-patient escalation regimen (RP2D-IE). The Phase I portion of the study was a standard 3+3 dose escalation design.The recommended Phase II dose of the intra-patient escalation dose regimen (RP2D-IE) was identified and expansion cohorts in metastatic uveal melanoma was accrued based on prior therapy.
Interventions
DRUGIMCgp100
Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3
Sponsors
Immunocore Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants age ≥ 18 years of age at the time of informed consent. 2. Ability to provide and understand written informed consent prior to any study procedures. 3. Histologically or cytologically confirmed diagnosis of metastatic uveal melanoma (mUM). 4. Surgically sterile participants or participants of child-bearing potential who agree to use highly effective methods of contraception during study dosing and for 6 months after last dose of study drug. 5. Human leukocyte antigen (HLA)-A\*0201 positive. 6. ECOG Performance Status of 0 or 1 at Screening. 7. Phase 2 will include participants with previously treated uveal melanoma in the metastatic setting.
Exclusion criteria
1. Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids. 2. History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies. 3. Participants with any out-of-range laboratory values. 4. Clinically significant cardiac disease or impaired cardiac function. 5. Active infection requiring systemic antibiotic therapy. 6. Known history of HIV infection. 7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. 8. Participants receiving systemic treatment with systemic steroid therapy or any other immunosuppressive medication at any dose level that would interfere with the action of the study drugs in the opinion of the investigator. 9. Malignant disease, other than that being treated in this study. 10. Any medical condition that would, in the investigator's judgment, prevent participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results. 11. Presence of NCI CTCAE ≥ grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ NCI CTCAE grade 3) due to prior cancer therapy. 12. Pregnant, likely to become pregnant, or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1 | Up to 49 months | Number of participants with a dose limiting toxicity, defined as an adverse event (AE) or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment and meets any of the pre-specified criteria. |
| Objective Response Rate in Phase 2 | Up to 38 months | Objective response rate (ORR) is defined as the percentage of participants with measurable disease with at least 1 visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an independent central review (ICR). The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | 24 weeks | Disease control rate (DCR) is defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) recorded at least 24 weeks (± 1 week) after commencement of study drug and prior to any progressive disease (PD) event, as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2. |
| Duration of Response | Up to 49 months | Duration of response (DOR) is defined as the time in months from the date of first documented objective response (CR or PR) until the date of documented disease progression or death by any cause in the absence of disease progression as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2. |
| Time to Response | Up to 49 months | Time to response (TTR) is defined as the time in months from the date of first dose of study drug until the date of first documented objective response as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2. |
| Overall Survival | Up to 49 months | Overall survival (OS) is defined as the time in months from the date of first dose of study drug until death due to any cause in general. |
| Minor Response Rate | Up to 49 months | Rate of minor response (or better) is defined as the proportion of participants with a confirmed CR, PR, or minor response (MinR) as assessed by RECIST v1.1 by the investigator for Phase 1 or ICR for Phase 2, where MinR is a reduction from baseline in sum of diameters between 10%-29%. The sum of diameters is defined as per RECIST v1.1 as the sum of longest diameters or short axis of target lesions (mm). |
| Objective Response Rate in Phase 1 | Up to 49 months | ORR is defined as the percentage of participants with measurable disease with at least 1 visit response of CR or PR that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an investigator. The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline. |
| Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose | The AUC was determined in in dose escalation cohorts. |
| Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose | The Cmax is determined in dose escalation cohorts. |
| Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose | The Tmax of tebentafusp is determined in dose escalation cohorts. |
| Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose | The t½ of tebentafusp is reported in dose escalation cohorts. |
| Percentage of Participants With Anti-IMCgp100 Antibody Formation | Up to 49 months | Overall antidrug antibody (ADA) is presented as number of ADA-positive participants relative to total number of participants with evaluable ADA results in each cohort |
| Number of Participants With Treatment Dose Interruptions or Reductions | Up to 49 months | Tolerability of study treatment was assessed by summarizing the number of participants with dose interruptions or reductions that occurred during the treatment period. |
| Progression-free Survival | Up to 49 months | Progression-free survival is defined as the time in months from first dose of study drug until the date of disease progression or death (by any cause in the absence of disease progression) as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2. |
Countries
Canada, Germany, Spain, United Kingdom, United States
Participant flow
Recruitment details
Of the 169 participants screened, 146 participants met the inclusion/exclusion criteria and were enrolled across 26 study centers in 5 countries.
Pre-assignment details
The data cut-off date for this analysis was on 20 Mar 2020. The first patient was enrolled on 29 Feb 2016 in the Phase 1 dose escalation cohorts and on 19 Jan 2017 in the Phase 2 dose expansion cohort.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 54 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days) | 3 |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 64 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days) | 6 |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 73 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days) | 4 |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 68 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days) | 6 |
| Phase 2 Dose Expansion: 68 mcg Tebentafusp Fixed low doses of 20 mcg tebentafusp at Cycle 1 Day 1 (C1D1) and 30 mcg at Cycle 1 Day 8 (C1D8), followed by weekly (QW) 68 mcg dose administered intravenously at Cycle 1 Day 15 (C1D15) and beyond (each cycle is 28 days) | 127 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 5 | 4 | 4 | 69 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Total | Phase 2 Dose Expansion: 68 mcg Tebentafusp | Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.3 Years STANDARD_DEVIATION 6.03 | 60.4 Years STANDARD_DEVIATION 11.05 | 61.0 Years STANDARD_DEVIATION 10.93 | 55.8 Years STANDARD_DEVIATION 9.24 | 56.5 Years STANDARD_DEVIATION 18.41 | 54.7 Years STANDARD_DEVIATION 11.99 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 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 |
| 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 | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 145 Participants | 126 Participants | 6 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 74 Participants | 64 Participants | 3 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 72 Participants | 63 Participants | 3 Participants | 2 Participants | 3 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 5 / 6 | 4 / 4 | 4 / 6 | 69 / 127 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 4 / 4 | 6 / 6 | 127 / 127 |
| serious Total, serious adverse events | 2 / 3 | 2 / 6 | 3 / 4 | 3 / 6 | 42 / 127 |
Outcome results
Primary
Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1
Number of participants with a dose limiting toxicity, defined as an adverse event (AE) or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment and meets any of the pre-specified criteria.
Time frame: Up to 49 months
Population: The Safety Analysis Set (SAS) included all participants who received at least 1 full or partial dose of tebentafusp.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1 | 0 Participants |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1 | 1 Participants |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1 | 2 Participants |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1 | 0 Participants |
Primary
Objective Response Rate in Phase 2
Objective response rate (ORR) is defined as the percentage of participants with measurable disease with at least 1 visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an independent central review (ICR). The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.
Time frame: Up to 38 months
Population: The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Objective Response Rate in Phase 2 | 4.7 Percentage of participants |
Secondary
Apparent Terminal Plasma Half-life (t½) of Tebentafusp
The t½ of tebentafusp is reported in dose escalation cohorts.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Population: All participants who received at least 1 full or partial dose of tebentafusp and with detectable serum concentrations are included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 1 | 6.635 Hours |
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 15 | 6.897 Hours |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 15 | 7.532 Hours |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 1 | 7.591 Hours |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 1 | 6.442 Hours |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 15 | 7.519 Hours |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 1 | 6.273 Hours |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Apparent Terminal Plasma Half-life (t½) of Tebentafusp | Cycle 1 Day 15 | 7.488 Hours |
Secondary
Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp
The AUC was determined in in dose escalation cohorts.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Population: All participants who received at least 1 full or partial dose of tebentafusp and with detectable serum concentrations are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 1 | 28550 hr*pg/mL | Standard Deviation 27 |
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 15 | 81310 hr*pg/mL | Standard Deviation 33.7 |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 15 | 98660 hr*pg/mL | Standard Deviation 34.8 |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 1 | 36530 hr*pg/mL | Standard Deviation 23.3 |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 1 | 32920 hr*pg/mL | Standard Deviation 18.2 |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 15 | 106800 hr*pg/mL | Standard Deviation 11.6 |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 1 | 33030 hr*pg/mL | Standard Deviation 16.5 |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp | Cycle 1 Day 15 | 109800 hr*pg/mL | Standard Deviation 23.3 |
Secondary
Disease Control Rate
Disease control rate (DCR) is defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) recorded at least 24 weeks (± 1 week) after commencement of study drug and prior to any progressive disease (PD) event, as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time frame: 24 weeks
Population: The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Disease Control Rate | 47.4 Percentage of participants |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Disease Control Rate | 22.8 Percentage of participants |
Secondary
Duration of Response
Duration of response (DOR) is defined as the time in months from the date of first documented objective response (CR or PR) until the date of documented disease progression or death by any cause in the absence of disease progression as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time frame: Up to 49 months
Population: The analysis population included all participants who received at least 1 full or partial dose of tebentafusp and who achieved a response. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Duration of Response | 7.425 Months |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Duration of Response | 8.706 Months |
Secondary
Maximum Plasma Concentration (Cmax) of Tebentafusp
The Cmax is determined in dose escalation cohorts.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Population: All participants who received at least 1 full or partial dose of tebentafusp and with detectable serum concentrations are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 1 | 3050 pg/mL | Standard Deviation 15.1 |
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 15 | 8885 pg/mL | Standard Deviation 17.2 |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 15 | 9523 pg/mL | Standard Deviation 23 |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 1 | 3294 pg/mL | Standard Deviation 22.7 |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 1 | 3041 pg/mL | Standard Deviation 21.7 |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 15 | 11300 pg/mL | Standard Deviation 11.7 |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 1 | 3640 pg/mL | Standard Deviation 23.3 |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Maximum Plasma Concentration (Cmax) of Tebentafusp | Cycle 1 Day 15 | 11520 pg/mL | Standard Deviation 25.8 |
Secondary
Minor Response Rate
Rate of minor response (or better) is defined as the proportion of participants with a confirmed CR, PR, or minor response (MinR) as assessed by RECIST v1.1 by the investigator for Phase 1 or ICR for Phase 2, where MinR is a reduction from baseline in sum of diameters between 10%-29%. The sum of diameters is defined as per RECIST v1.1 as the sum of longest diameters or short axis of target lesions (mm).
Time frame: Up to 49 months
Population: The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Minor Response Rate | 26.3 Percentage of participants |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Minor Response Rate | 11.0 Percentage of participants |
Secondary
Number of Participants With Treatment Dose Interruptions or Reductions
Tolerability of study treatment was assessed by summarizing the number of participants with dose interruptions or reductions that occurred during the treatment period.
Time frame: Up to 49 months
Population: The Safety Analysis Set (SAS) included all participants who received at least 1 full or partial dose of tebentafusp.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Number of Participants With Treatment Dose Interruptions or Reductions | 2 Participants |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Number of Participants With Treatment Dose Interruptions or Reductions | 4 Participants |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Number of Participants With Treatment Dose Interruptions or Reductions | 3 Participants |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Number of Participants With Treatment Dose Interruptions or Reductions | 4 Participants |
| Phase 2 Dose Expansion | Number of Participants With Treatment Dose Interruptions or Reductions | 49 Participants |
Secondary
Objective Response Rate in Phase 1
ORR is defined as the percentage of participants with measurable disease with at least 1 visit response of CR or PR that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an investigator. The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.
Time frame: Up to 49 months
Population: The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Objective Response Rate in Phase 1 | 15.8 Percentage of participants |
Secondary
Overall Survival
Overall survival (OS) is defined as the time in months from the date of first dose of study drug until death due to any cause in general.
Time frame: Up to 49 months
Population: The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Overall Survival | 29.6 Months |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Overall Survival | 16.8 Months |
Secondary
Percentage of Participants With Anti-IMCgp100 Antibody Formation
Overall antidrug antibody (ADA) is presented as number of ADA-positive participants relative to total number of participants with evaluable ADA results in each cohort
Time frame: Up to 49 months
Population: The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp and with evaluable data; two participants were excluded from ADA evaluation due to lack of sampling after dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Percentage of Participants With Anti-IMCgp100 Antibody Formation | 66.7 Percentage of participants |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Percentage of Participants With Anti-IMCgp100 Antibody Formation | 16.7 Percentage of participants |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Percentage of Participants With Anti-IMCgp100 Antibody Formation | 25.0 Percentage of participants |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Percentage of Participants With Anti-IMCgp100 Antibody Formation | 33.3 Percentage of participants |
| Phase 2 Dose Expansion | Percentage of Participants With Anti-IMCgp100 Antibody Formation | 33.6 Percentage of participants |
Secondary
Progression-free Survival
Progression-free survival is defined as the time in months from first dose of study drug until the date of disease progression or death (by any cause in the absence of disease progression) as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time frame: Up to 49 months
Population: The Full Analysis Set (FAS) included all participants who received at least 1 full or partial dose of tebentafusp. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Progression-free Survival | 7.4 Months |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Progression-free Survival | 2.8 Months |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Tebentafusp
The Tmax of tebentafusp is determined in dose escalation cohorts.
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Population: All participants who received at least 1 full or partial dose of tebentafusp and with detectable serum concentrations are included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 1 | 0.50 Hours |
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 15 | 0.50 Hours |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 15 | 0.50 Hours |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 1 | 0.50 Hours |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 1 | 0.50 Hours |
| Phase 1 Dose Escalation Cohort 3: 73 mcg Tebentafusp | Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 15 | 0.50 Hours |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 1 | 0.50 Hours |
| Phase 1 Dose Escalation Cohort 4: 68 mcg Tebentafusp | Time to Maximum Plasma Concentration (Tmax) of Tebentafusp | Cycle 1 Day 15 | 0.50 Hours |
Secondary
Time to Response
Time to response (TTR) is defined as the time in months from the date of first dose of study drug until the date of first documented objective response as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time frame: Up to 49 months
Population: The analysis population included all participants who received at least 1 full or partial dose of tebentafusp and who achieved a response. The analysis was pre-specified to be a pooled analysis of all Phase 1 cohort participants (irrespective of dose); therefore, data by individual dose were not analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 Dose Escalation Cohort 1: 54 mcg Tebentafusp | Time to Response | 5.5 Months | Standard Deviation 1.8 |
| Phase 1 Dose Escalation Cohort 2: 64 mcg Tebentafusp | Time to Response | 7.0 Months | Standard Deviation 6.9 |