CDR404

Shet Biswas Chief Medical Officer, CDR-Life

Lauren Miro

Gilberto de Lima Lopes, MD

Cancer Answer Line

Paul Swiecicki, MD

Providence Cancer Institute

Rom Leidner, MD

Research Team

Mark Diamond, MD

Phase 1 Unit

Iben Spanggaard, MD

CDR404 is a highly potent and specific T-cell engaging bispecific and bivalent antibody designed for the treatment of cancers positive for the tumor-associated antigen melanoma-associated antigen 4 (MAGE-A4). This is a first-in-human study designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of CDR404 in adult patients who have the appropriate germline human leukocyte antigen HLA-A\*02:01 tissue marker and whose cancer is positive for MAGE-A4.

The CDR404-001 Phase 1 study will enrol patients with locally advanced, unresectable or metastatic tumors expressing MAGE-A4, which include advanced solid tumors, and will be conducted in multiple phases:

1. To identify the maximum tolerated dose (MTD) and pharmacologically effective dose range (PEDR) for CDR404
2. To assess preliminary evidence of anti-tumor activity of CDR404
3. To characterise the pharmacokinetics of CDR404
4. To characterise the immunogenicity of CDR404
5. To assess translational biomarkers

First in Human Study of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors

Phase 1, First-in-Human Study to Assess the Safety, Tolerability and Anti-tumor Activity of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors

following single and multiple dose administration

to the end of the dosing interval following single and multiple dose administration

Incidence of detectable anti-CDR404 antibodies (ADAs)

CDR-Life AG

All Drugs and Chemicals

Immunomodulating Agents

Muromonab-CD3

Four fixed-dose, dose escalation cohorts (Cohorts 1 to 4) and 3 intrapatient dose escalation cohorts (Cohorts 5 to 7) to establish the MTD/RP2D of IMCnyeso.

Three planned cohorts treated at the RP2D to make a preliminary assessment of the anti-tumor activity of IMCnyeso. Phase 2 was not initiated and data were not collected.

IMCnyeso

Study Director

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.

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).

Safety and Efficacy of IMCnyeso in Advanced NY-ESO-1 and/or LAGE-1A Positive Cancers

A Phase I/II Study of IMCnyeso, HLA- A*0201-Restricted, NY-ESO-1- and LAGE-1A-specific Soluble T Cell Receptor and Anti-CD3 Bispecific Molecule, in HLA-A*0201 Positive Patients With Advanced NY-ESO-1 and/or LAGE - 1A Positive Cancer

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

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.

Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions

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.

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.

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.

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.

Overall Survival is defined as the time (in months) from the date of randomization to the date of death due to any cause.

Number of participants with positive treatment-boosted or treatment-induced anti-IMCnyeso antibody titers

Immunocore Ltd

The Safety Analysis Set includes all participants who received at least 1 full or partial dose of study drug in Phase 1; the Phase 2 arm was not started and no data were collected. One participant was sequentially enrolled in two cohorts (10 mcg and 30-100 mcg). Events in either cohort are counted once in the total cohort.

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

Phase 1: IMCnyeso 3 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

Phase 1: IMCnyeso 10 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

Phase 1: IMCnyeso 30 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

Phase 1: IMCnyeso 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)

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 on Cycle 1 Day 8, then 180 mcg starting on Cycle 1 Day 15)

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 300 mcg starting on Cycle 1 Day 15)

Phase 1: IMCnyeso 30-100-300 mcg

Total

18-64 years old

65-84 years old

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Melanoma

Synovial sarcoma

Urothelial carcinoma

Non-small cell lung cancer

Original cancer diagnosis

The Full Analysis Set includes all participants assigned to treatment who receive at least 1 full or partial dose of study drug; one participant that sequentially enrolled in two cohorts (10 mcg and 30-100 mcg) is represented in the 30-100 mcg cohort.

The Safety Analysis Set includes all participants who received at least 1 full or partial dose of study drug.

Phase 1: Number of Participants With Dose-limiting Toxicities

Any treatment-emergent adverse event (TEAE)

Any TEAE Grade ≥3

Any TEAE leading to death

Phase 1: Number of Participants With Adverse Events

No dose interruption at any time

No dose reduction at any time

Phase 1: Number of Participants With No Dose Interruptions or Reductions

Three planned cohorts treated at the RP2D to make a preliminary assessment of the anti-tumor activity of IMCnyeso. The Phase 2 arm was not initiated.

Phase 2: Dose Expansion

The study was terminated during Phase 1 due to strategic reasons; data were not collected or analyzed for any Phase 2 outcome measures.

Phase 2: Best Overall Response (BOR)

Phase 2: Number of Participants With Adverse Events

The study was terminated during Phase 1 due to strategic reasons; data were not collected or analyzed for any Phase 2 outcome measures

Phase 2: Number of Participants With No Dose Interruptions or Reductions

Complete Response

Partial Response

Stable Disease

Progressive Disease

Non-evaluable

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.

Phase 1: Number of Participants With Best Overall Response (BOR)

IMCnyeso 30-100-300 mcg

The study was terminated during Phase 1 due to strategic reasons; data were not collected or analyzed for this outcome measure in Phase 2.

Phase 1 and Phase 2: Progression-free Survival

Phase 1: Dose Escalation

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.

Phase 1 and Phase 2: Duration of Response

Phase 1 and Phase 2: Overall Survival

Cycle 1 Day 1

Cycle 1 Day 15

The pharmacokinetic analysis set includes participants in the safety analysis set with at least 1 post-dose sample providing evaluable data.

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last)

The pharmacokinetic analysis set includes participants in the safety analysis set with at least 1 post-dose sample providing evaluable data

Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax)

Time to Reach Maximum Plasma Concentration (Tmax)

Number of Participants With Anti-IMCnyeso Antibody Formation

Overall Study

Antineoplastic Agents

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease (PD), or development of other reason for treatment discontinuation.

MEDI0562

The purpose of this study is to evaluate MEDI0562 in combination with immune therapeutic agents in adult subjects with select advanced solid tumors.

This is a Phase 1 multicenter, open-label study to evaluate the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of MEDI0562 in combination with immune therapeutic agents in adult subjects with select advanced solid tumors.

A Study to Evaluate MEDI0562 in Combination With Immune Therapeutic Agents in Adult Subjects With Advanced Solid Tumors

A Phase 1 Multicenter, Open-label, Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Antitumor Activity of MEDI0562 in Combination With Immune Therapeutic Agents in Adult Subjects With Advanced Solid Tumors

The primary endpoint is safety as assessed by presence of adverse event (AE), serious adverse event (SAE), and dose limiting toxicity (DLT).

The endpoints for assessment of antitumor activity include Best Overall Response (BOR) and will be based on all post-baseline disease assessments that occur prior to the initiation of subsequent anticancer therapy

The endpoints for assessment of PK of MEDI0562 and durvalumab or tremelimumab include individual MEDI0562, durvalumab, and tremelimumab concentrations at different time points after administration. PK parameters that may be modeled on these data include, but are not limited to, maximum observed concentration (Cmax).

The endpoints for assessment of immunogenicity of MEDI0562, durvalumab, and tremelimumab include the number and percentage of subjects who develop detectable anti drug antibodies (ADAs).

The endpoints for assessment of pharmacodynamic activity include induction of proliferation markers in various lymphocyte populations and assessment of tumor-infiltrating lymphocytes (TILs) in tumor biopsy specimens.

The endpoints for assessment of antitumor activity include disease control and is defined as CR, PR, or SD according to RECIST v1.1

The endpoints for assessment of antitumor activity include duration of response (DoR) and is defined as the duration from the first documentation of OR to the first documentation of disease progression or death due to any cause.

The endpoints for assessment of antitumor activity include progression-free survival (PFS) and is defined as the duration measured from the start of treatment with investigational product to the first documentation of disease progression or death due to any cause

The endpoints for assessment of antitumor activity include overall survival (OS) and is defined as the time from the start of treatment with Investigational Product until death due to any cause.

The endpoints for assessment of PK of MEDI0562 and durvalumab or tremelimumab include individual MEDI0562, durvalumab, and tremelimumab concentrations at different time points after administration. PK parameters that may be modeled on these data include area under the concentration-time curve (AUC).

The endpoints for assessment of PK of MEDI0562 and durvalumab or tremelimumab include individual MEDI0562, durvalumab, and tremelimumab concentrations at different time points after administration. PK parameters that may be modeled on these data include clearance (CL).

The endpoints for assessment of PK of MEDI0562 and durvalumab or tremelimumab include individual MEDI0562, durvalumab, and tremelimumab concentrations at different time points after administration. PK parameters that may be modeled on these data include terminal phase half-life (t½).

The endpoints for assessment of antitumor activity include objective response (OR) and is defined as confirmed CR or confirmed PR based on RECIST v1.1

The endpoints for assessment of Time to Response TTR and is defined as the time of first treatment to a subsequently confirmed CR or confirmed PR based on RECIST v1.1

The endpoints for assessment percent change from baseline in target lesion sum of diameters will be calculated at each adequate post baseline disease assessment with recorded measurement for all target lesions defined at baseline.

MedImmune LLC

Antibodies

Antibodies, Monoclonal

Bevacizumab

Pembrolizumab

Immunoglobulins

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Immune Checkpoint Inhibitors

Participants receive IMC-F106C and pembrolizumab.

Participants receive IMC-F106C and chemotherapy. Choice of chemotherapy is dependent on cohort.

Participants receive IMC-F106C and a selected targeted therapy. Receipt of kinase inhibitor is dependent on histology.

Participants receive IMC-F106C, biologics (eg, pembrolizumab, bevacizumab) IV infusions and chemotherapy IV infusions based on histology.

IMC-F106C

IMC-F106C and pembrolizumab

IMC-F106C and chemotherapy

IMC-F106C and a monoclonal antibody therapy and chemotherapy

IMC-F106C and monoclonal antibodies and chemotherapy

IMC-F106C and tebentafusp

IMC-F106C and bevacizumab

IMC-F106C and kinase inhibitors

Immunocore Medical Information

Immunocore Medical Information EU

IMC-F106C is an immune-mobilizing monoclonal T cell receptor against cancer (ImmTAC ®) designed for the treatment of cancers positive for the tumor-associated antigen PRAME. This is a first-in-human trial designed to evaluate the safety and efficacy of IMC-F106C in adult patients who have the appropriate HLA-A2 tissue marker and whose cancer is positive for PRAME.

The IMC-F106C-101 Phase 1/2 study will be evaluated in patients with metastatic/unresectable tumors which include select Advanced Solid Tumors and will be conducted in two phases.

1. Phase 1: To identify the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 dose (RP2D) of IMC-F106C as a single agent and administered in combination with chemotherapies, targeted therapies, and monoclonal antibodies.
2. Phase 2: To assess the efficacy of IMC-F106C in selected advanced solid tumors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
First in Human Study of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors	NCT06402201	Select Advanced...	CDR404	18 Years -	CDR-Life AG
First in Human Study of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors	NCT06402201	Select Advanced...	CDR404	18 Years -	CDR-Life AG
First in Human Study of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors	NCT06402201	Select Advanced...	CDR404	18 Years -	CDR-Life AG
Safety and Efficacy of IMCnyeso in Advanced NY-ESO-1 and/or LAGE-1A Positive Cancers	NCT03515551	Select Advanced...	IMCnyeso	18 Years -	Immunocore Ltd
A Study to Evaluate MEDI0562 in Combination With Immune Therapeutic Agents in Adult Subjects With Advanced Solid Tumors	NCT02705482	Select Advanced...	MEDI0562 Tremelimumab Durvalumab	18 Years - 100 Years	MedImmune LLC
Safety and Efficacy of IMC-F106C as a Single Agent and in Combination With Checkpoint Inhibitors	NCT04262466	Select Advanced...	IMC-F106C IMC-F106C and p... IMC-F106C and c... IMC-F106C and m... IMC-F106C and t... IMC-F106C and b... IMC-F106C and k...	18 Years -	Immunocore Ltd

Spots Global Cancer Trial Database for select advanced solid tumors