Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Nevus, Pigmented

Nevus

Nevus, Blue

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Acral Lentiginous Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Atezolizumab

Immunomodulating Agents

Muromonab-CD3

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tebentafusp in combination with Pembrolizumab

Straight to on protocol survival follow up including investigators choice of therapy

soluble gp100-specific T cell receptor with anti-CD3 scFV

Tebentafusp

soluble gp100-specific T cell receptor with anti-CD3 scFV in combination with Pembrolizumab

Tebentafusp with Pembrolizumab

Investigators Choice

Immunocore Medical Information

Immunocore Medical Information EU

To evaluate the efficacy and safety of tebentafusp-based regimens tebentafusp monotherapy and in combination with anti-PD1 vs investigator choice (including clinical trials of investigational agents, salvage therapy per local standard of care (SoC), best supportive care (BSC)) on protocol survivor follow up) in patients with advanced non-ocular melanoma

This is a Phase 2/3, multicenter, open-label study to evaluate the efficacy and safety of tebentafusp as monotherapy (Arm A) and in combination with pembrolizumab (Arm B) compared with standard of care or best supportive care (Arm C) in participants with non-ocular advanced melanoma who have progressed on a prior anti-PD(L)1 regimen, received prior ipilimumab and, if the participant has a BRAF mutation, a prior BRAF tyrosine kinase inhibitor (TKI) regimen.

Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)

Phase 2/3 Randomized Study of Tebentafusp as Monotherapy and in Combination With Pembrolizumab Versus Investigator's Choice in HLA-A*02:01-positive Participants With Previously Treated Advanced Melanoma (TEBE-AM)

ctDNA reduction on treatment relative to baseline

Incidence and severity of AEs, SAEs and changes from baseline in laboratory parameters, vital signs, and ECGs

Dose Interruptions and discontinuations; Dose Reductions

Tebentafusp concentration. Tebentafusp PK parameters (eg, Cmax, Tmax, Cavg, t1/2)

Immunocore Ltd

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Tremelimumab

IV Tebentafusp (IMCgp100) with durvalumab (MEDI4736)

IV Tebentafusp (IMCgp100) with tremelimumab

IV Tebentafusp (IMCgp100) with durvalumab (MEDI4736) and tremelimumab

Tebentafusp (IMCgp100) (single agent) subcutaneous injection

Tebentafusp (IMCgp100)

durvalumab

tremelimumab

This study is a Phase Ib/II, multi-center, open-label study of tebentafusp (IMCgp100) as a single agent and in combination with durvalumab (MEDI4736) and/or tremelimumab in metastatic cutaneous melanoma. The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and to evaluate the anti-tumor activity of tebentafusp (IMCgp100) in combination with durvalumab (MEDI4736, programmed death-ligand 1 \[PD-L1\] inhibitor), tremelimumab (CLTA-4 inhibitor), and the combination of durvalumab with tremelimumab compared to single-agent tebentafusp (IMCgp100) alone administered as an intravenous or subcutaneous. The study will enroll patients who have metastatic melanoma that is refractory to treatment with an anti-PD-1 inhibitor in the metastatic setting. This study will also evaluate the safety, tolerability, and anti-tumor activity of tebentafusp (IMCgp100) monotherapy in patients with advanced non-uveal melanoma who progressed on prior PD-1 inhibitors approved for the treatment of advanced melanoma; patients with BRAF mutations must be refractory to approved BRAF-based therapy.

Recent biologic evidence indicates that optimal responses to programmed cell death-1 (PD-1) directed therapy require the presence of CD8+ T cells in the tumor microenvironment and thus therapies such as tebentafusp (IMCgp100) that recruit these effector cells to the tumor may overcome pre-existing resistance to checkpoint blockade. This emerging biology of checkpoint inhibitor resistance suggests the combination of tebentafusp (IMCgp100) with checkpoint inhibition may have enhanced activity in patients with pre-existing resistance.

Phase 1b/2 Study of the Combination of IMCgp100 With Durvalumab and/or Tremelimumab in Advanced Cutaneous Melanoma

A Phase Ib/II Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 in Combination With Durvalumab (MEDI4736) or Tremelimumab or the Combination of Durvalumab and Tremelimumab Compared to IMCgp100 Alone in Patients With Advanced Melanoma

The number of dose-limiting toxicities (DLT) observed during the DLT observation period. DLT observation period for the Arms 1 to 3 Phase Ib cohorts will be the first 2 cycles of treatment (C1D1 until C2D28). The DLT observation period for Arm 4 Phase Ib will be from C1D22 to C2D14. A DLT is defined as an adverse event or abnormal laboratory value that occurs during the relevant DLT period which is assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications, occurs during the DLT Observation Period or is Grade 3 or higher per NCI CTCAE version 4.03, or as specified in the protocol.

Objective Response Rate (RECIST v1.1) Objective response rate, defined as the proportion of patients with a best response of CR or PR based on investigator assessment, as defined in RECIST v1.1.

Time from the date of first dose until death due to any cause.

Safety incidence and severity of AEs and SAEs including changes in laboratory. parameters, vital signs, and electrocardiograms (ECG).

AUClast : Area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1)

AUCinf : The AUC from time zero to infinity (mass x time x volume-1)

Tmax: The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)

t1/2 : Elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time)

Correlation of gp100 and PD-L1 expression by immunohistochemistry evaluated in pre-treatment biopsies with anti-tumor activity.

Time from the date of first documented response until date of documented progression or death in the absence of disease progression. The median duration of response and corresponding 90% confidence interval will be presented.

Time from initiation of therapy to the time that an OR per RECISTv1.1 is achieved.

Proportion of patients with either a best response of PR or CR or with SD over 24 weeks after first dose in the study. The DCR and associated 90% confidence interval will be presented by treatment arm.

Incidence of anti-IMCgp100, anti-durvalumab, and anti-tremelimumab antibody formation following multiple infusions of IMCgp100 alone and in combination with durvalumab and/or tremelimumab.

AstraZeneca

Weekly intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.

Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle.

For each arm, the study will be divided into two parts: In part 1, dose escalation, the MTD or RP2D for each dosing regimen will be established. In part 2, dose expansion, a cohort of participants will be treated at the RP2D or MTD.

IMCgp100

Namir Hassan, PhD

IMCgp100 is a new biological therapy designed for the treatment of melanoma skin cancer. The drug is designed to target melanoma cells and stimulate immune cells to kill them. This trial is designed to establish the level of drug that can be given to a patient that is tolerable. It also designed to establish the best dosing schedule for the drug and to look for signals that the drug is working as intended.

IMCgp100 is a bispecific biologic incorporating an engineered T cell receptor (TCR) specific for a peptide antigen derived from the protein gp100 presented in the context of HLA A2 on the surface of melanoma cells. The TCR is fused to an anti-CD3 antibody single-chain variable fragment (scFv) that recruits and activates non-melanoma specific T cells (killer T cells) in physical contact with the cancer T cell. This is a Phase I study designed to assess the safety profile and establish a tolerable dose of IMCgp100 in HLA A2 positive malignant melanoma patients. The study has two treatment arms with different treatment schedules, weekly or daily dosing. Each treatment arm in the study has two parts. In the first part, dose escalation, the safety and tolerability of the drug are examined and the optimal dose of drug is established. In the second part of the trial, participants will receive an extended course of treatment with a view to assessing the effect of the drug on disease.

Study to Assess the Tolerability of a Bispecific Targeted Biologic IMCgp100 in Malignant Melanoma

A Phase 1, Open Label, Dose Finding Study to Assess the Safety and Tolerability of IMCgp100, a Monoclonal T Cell Receptor Anti-CD3 scFv Fusion Protein in Patients With Advanced Malignant Melanoma

The maximum tolerated dose (MTD) for IMCgp100 administered by weekly dosing was determined based on the frequency of dose-limiting toxicity (DLT) occurring during Days 1 to 8. Participants presented at MTD in the dose escalation phase.

Abbreviations: ng/kg=nanograms/kilogram

The MTD for IMCgp100 administered by daily dosing was determined based on the frequency of DLT occurring during Days 1 to 8. The 50 mcg dose was the RP2D for daily dosing, as the MTD was not achieved.

Abbreviations: mcg=micrograms

Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) with an onset date after the date of first dose and within 30 days after the last administration of study medication in either treatment arm. AEs with missing date of onset were considered treatment emergent.

Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

Laboratory parameters included clinical chemistry, hematology, and urinalysis. For hematology, this included red cell count, hemoglobin, hematocrit, mean cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, leukocyte differential count (percentage or absolute), prothrombin time, and activated partial tissue thromboplastin time. Laboratory parameter abnormalities were graded by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

Laboratory parameters included clinical chemistry, hematology, and urinalysis. Clinical chemistry parameters included calcium, phosphorus, magnesium, albumin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, lactate dehydrogenase, sodium, potassium, bicarbonate, creatinine, chloride, glucose, urea, uric acid, and C-reactive protein. Laboratory parameter abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose.

Vital signs included temperature, blood pressure, respiration rate, and heart rate. Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Blood pressure and heart rate were measured using a recording device with an appropriate cuff size. Temperature and respiration rate were measured as per clinical practice. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose.

Physical examination included weight, a record of skin pigmentation, and photographic record of any vitiligo if present. Abnormalities were graded by the investigator using CTCAE v 4.0 at any time on treatment from normal pre-dose. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death.

The best overall response was assigned as complete response (CR), partial response (PR), minor response, stable disease, progressive disease (PD) or not evaluable (NE) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

To provide a comprehensive anti-drug antibody (ADA) summary for the study, individual participant data were combined and assessed as distinct groups based on characteristics of their ADA response. Evaluable participants were those with post-drug administration samples. ADA prevalence (pre- existing antibody response) was measured as the number of baseline-positive participant out of all participants who provided baseline samples. Overall ADA incidence was calculated based on the combined number of treatment-boosted and treatment-induced ADA-positive participants. The treatment-induced incidence was determined as the number of ADA- positive participants of those that were ADA-negative at baseline; while treatment-boosted incidence was determined as the number of participants with an ADA titer increase equal to or greater than the minimum significant dilution (3-fold) of the assay.

The maximum plasma concentration (Cmax) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: ng/kg = nanograms/kilogram

The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.

The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. Abbreviations: mcg = micrograms

The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. On Day 1, IMCgp100 20 mcg was given, IMCgp100 30 mcg was administered on Day 8, and IMCgp100 50 mcg was dosed on Days 15 and after.

The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. This dosing regimen was implemented following the Urgent Safety Measure to adapt the dosing in the Phase 1 study that dropped Dose 1 to 40 mcg from the identified 50 mcg RP2D.

The Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The RP2D identified in this study following review of all safety and pharmacokinetic data in the dose escalation of the Phase 1 study was the 50 mcg flat dose.

The area under the concentration-time curve (AUC), measured in hours by picograms per milliliter ( h\*pg/ml) is a method of measurement of the total exposure of a drug in blood.

The AUC, measured in h\*pg/ml, is a method of measurement of the total exposure of a drug in blood.

The AUC (measured in h\*pg/ml) is a method of measurement of the total exposure of a drug in blood. Participants in the 20 mcg and 40 mcg dose groups received intra-participant dose-escalation up to 50 mcg on Day 15.

The AUC (measured in h\*pg/ml) is a method of measurement of the total exposure of a drug in blood.

Adverse events were recorded from the time informed consent was obtained to 30 days after the final dose or 30 days after withdrawal from treatment. The safety population was comprised of the 84 participants who enrolled in the study and included all participants who received at least one dose of IMCgp100.

Weekly intravenous (IV) infusions of IMCgp100 at the weekly maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) over treatment cycles of eight weeks each.

IMCgp100 Weekly Dosing Regimen

Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six week treatment cycle at the MTD/daily RP2D.

IMCgp100 Daily Dosing Regimen

Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment cycle

Total

Age, Continuous

Sex: Female, Male

White

Black

Asian

Other

Race/Ethnicity, Customized

Safety population: The all-patients population and the safety population both comprised the 84 participants who enrolled in the study and who also received at least one IMCgp100 dose.

Chris Holland, Executive Director Head of Biostatistics

Safety population: all participants who received at least 1 dose of IMCgp100, up to a maximum of 600 ng/kg.

Maximum Tolerated Dose (MTD) of IMCgp100 Administered Weekly (Dose Escalation Part)

Daily intravenous (IV) infusions of IMCgp100 over treatment cycles of 8 weeks each.

Safety population: all participants who received at least 1 dose of IMCgp100

MTD of IMCgp100 Administered Daily (Dose Escalation Part)

Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

Lymphocytes

Hemoglobin

Neutrophils

CD4 Cells

Leukocytes

Daily IV infusions of IMCgp100 administered on days 1 to 4 and days 22 to 25 of a six-week treatment.

Number of Participants Experiencing Clinically Significant Laboratory Parameters (Hematology)

Lymphocytes-Grade 3

Lymphocytes-Grade 4

CD4 Count-Grade 3

CD4 Count-Grade 4

Hemoglobin-Grade 3

Leukocytes-Grade 3

Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Hematology)

Albumin

Alkaline Phosphatase

Aspartate Aminotransferase

Alanine Aminotransferase

Potassium

Calcium

Glucose

Magnesium

Sodium

Uric Acid

Number of Participants Experiencing Clinically Significant Laboratory Parameters (Clinical Chemistry)

Sodium-Grade 3

Potassium-Grade 3

Glucose-Grade 3

Aspartate Aminotransferase-Grade 3

Calcium-Grade 3

Number of Participants Experiencing ≥Grade 3 Severity in Laboratory Parameters (Clinical Chemistry)

Number of Participants Experiencing Clinically Significant Electrocardiograms (ECGs)

High Systolic Blood Pressure

Low Systolic Blood Pressure

High Diastolic Blood Pressure

Low Diastolic Blood Pressure

High Heart Rate

Low Heart Rate

High Temperature

Number of Participants Experiencing Clinically Significant Vital Signs

Number of Participants Experiencing Clinically Significant Physical Examination Results (Weight Decrease)

Number of Participants Experiencing ≥Grade 3 Severity in Physical Examination Results (Skin Pigmentation)

Efficacy population: only evaluable participants (those having both a baseline and post treatment sample).

Number of Participants With Best Overall Response Per Response Evaluation Criteria In Solid Tumors (RECIST) (Weekly Dosing-Dose Expansion Part)

Number of Participants With Anti-IMCgp100 Antibody Formation (Dose Escalation and Dose Expansion Parts)

15 ng/kg by-weight dose

45 ng/kg by-weight dose

135 ng/kg by-weight dose

270 ng/kg by-weight dose

405 ng/kg by-weight dose

600 ng/kg by-weight dose

900 ng/kg by-weight dose

Pharmacokinetics (PK) Population: all participants who receive at least 1 dose of IMCgp100 and have at least 1 measurable PK concentration with the relevant date, time and dosing data for this sample.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)	NCT05549297	Advanced Melano...	Tebentafusp Tebentafusp wit... Investigators C...	18 Years -	Immunocore Ltd
Phase 1b/2 Study of the Combination of IMCgp100 With Durvalumab and/or Tremelimumab in Advanced Cutaneous Melanoma	NCT02535078	Malignant Melan...	Tebentafusp (IM... durvalumab tremelimumab	18 Years -	Immunocore Ltd
Study to Assess the Tolerability of a Bispecific Targeted Biologic IMCgp100 in Malignant Melanoma	NCT01211262	Malignant Melan...	IMCgp100	18 Years -	Immunocore Ltd
Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma	NCT03070392	Uveal Melanoma	IMCgp100 Dacarbazine Ipilimumab Pembrolizumab	18 Years - 99 Years	Immunocore Ltd
IMCgp100-401 Rollover Study	NCT02889861	Malignant Melan...	IMCgp100	18 Years -	Immunocore Ltd
Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma	NCT03070392	Uveal Melanoma	IMCgp100 Dacarbazine Ipilimumab Pembrolizumab	18 Years - 99 Years	Immunocore Ltd
A Cohort IND Expanded Access Program for Supporting Patient Access to Tebentafusp	NCT04960891	Uveal Melanoma	Tebentafusp	18 Years -	Immunocore Ltd

Spots Global Cancer Trial Database for imcgp100

Every month we try and update this database with for imcgp100 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for imcgp100

Every month we try and update this database with for imcgp100 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for imcgp100 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.