NCT05104567

A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203)

Completed Phase 2 Results posted Last updated 24 September 2025

What this trial tests

Phase 2 trial testing THOR-707 in Oesophageal Squamous Cell Carcinoma in 138 participants. Completed in 9 September 2024.

Timeline

9 December 2021

Primary endpoint
26 July 2023

9 September 2024

Quick facts

Lead sponsor	Sanofi
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	138
Start date	9 December 2021
Primary completion	26 July 2023
Estimated completion	9 September 2024
Sites	29 locations across France, Italy, Netherlands, Belgium, Chile, South Korea, China, United States

Drugs / interventions tested

• THOR-707 — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →
• Cetuximab (cetuximab) — full drug profile →

Conditions studied

• Oesophageal Squamous Cell Carcinoma — all drugs for Oesophageal Squamous Cell Carcinoma →
• Gastric Cancer — all drugs for Gastric Cancer →
• Hepatocellular Carcinoma — all drugs for Hepatocellular Carcinoma →
• Colorectal Cancer — all drugs for Colorectal Cancer →

Sponsor

Sanofi — full company profile →

Who can join

18 and older, any sex, with Oesophageal Squamous Cell Carcinoma or Gastric Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cohort A: Objective Response Rate (ORR) Primary · From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 millimeter (mm) (\<1 centimeter \[cm\]). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Group	Value	95% CI
Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	20.0	1.0 – 65.7

Cohorts B1, B2 and B3: Objective Response Rate Primary · From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 25 months

ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Group	Value	95% CI
CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy	13.6	3.8 – 31.6
CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy	5.3	0.3 – 22.6
Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy	11.1	2.0 – 31.0

Cohort C: Objective Response Rate Primary · From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 20 months

ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Group	Value	95% CI
Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	5.0	0.3 – 21.6

Cohorts D1 and D2: Objective Response Rate Primary · From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months

ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Group	Value	95% CI
Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy	0	0.0 – 9.5
Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy	8.3	1.5 – 24.0

All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Secondary · From first dose of study treatment administration (Day 1) up to 30 days post last dose of study treatment administration, up to approximately 9 months (Cohorts A, D1 and D2), 26 months (Cohorts B1, B2 and B3) and 21 months (Cohort C)

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened (according to the Investigator's opinion) or became ser

TEAEs

Group	Value	95% CI
Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	5
CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy	22
CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy	19
Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy	18
Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	19
Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy	30
Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy	24

TESAEs

Group	Value	95% CI
Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	2
CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy	17
CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy	13
Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy	9
Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	7
Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy	19
Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy	11

All Cohorts: Time to Response (TTR) Secondary · From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

TTR was defined as the time from the date of first study treatment administration to the first tumor assessment at which the overall response was recorded as PR or CR that was subsequently confirmed as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Group	Value	95% CI
Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	1.9	± NA
CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy	2.1	± 0.2
CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy	4.2	± NA
Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy	3.0	± 1.3
Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	6.0	± NA
Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy	2.0	± 0.1

All Cohorts: Duration of Response (DOR) Secondary · From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

DOR was defined as the time from the date of first tumor assessment at which the overall response was recorded as CR or PR that was subsequently confirmed to the date of first documentation of objective PD before the initiation of any post-treatment anti-cancer therapy or death due to any cause, whichever occurred first, as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions

Group	Value	95% CI
Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	NA	NA – NA
CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy	13.1	NA – NA
CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy	NA	NA – NA
Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy	8.8	8.6 – NA
Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	NA	NA – NA
Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy	4.1	4.1 – NA

All Cohorts: Clinical Benefit Rate (CBR) Secondary · From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

CBR was defined as the percentage of participants with clinical benefit (confirmed CR or PR as best overall response \[BOR\], or SD lasting at least 6 months), as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. BOR was defined as the best response recorded from the start of the study treatment until disease progression/rec

Group	Value	95% CI
Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	40.0	7.6 – 81.1
CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy	22.7	9.4 – 42.0
CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy	10.5	1.9 – 29.6
Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy	11.1	2.0 – 31.0
Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	10.0	1.8 – 28.3
Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy	6.7	1.2 – 19.5
Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy	12.5	3.5 – 29.2

All Cohorts: Progression-Free Survival (PFS) Secondary · From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

PFS was defined as the time from the date of first study treatment to the date of the first documentation of objective PD or death due to any cause, whichever occurred first, as per RECIST v 1.1. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).

Group	Value	95% CI
Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	NA	2.2 – NA
CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy	1.9	1.2 – 2.9
CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy	2.0	1.4 – 3.5
Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy	2.1	1.8 – 2.2
Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy	2.1	1.9 – 2.2
Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy	2.0	1.9 – 2.1
Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy	2.1	2.0 – 4.1

Maximum Concentration Observed (Cmax) of Pegenzileukin Secondary · Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

Blood samples were collected at specified timepoints for the assessment of Cmax of pegenzileukin. The pharmacokinetic (PK) parameters were calculated using non-compartmental method.

Day 1 Cycle 1

Group	Value	95% CI
All Cohorts: Pegenzileukin 24 mcg/kg	417	± 109

Day 1 Cycle 4

Group	Value	95% CI
All Cohorts: Pegenzileukin 24 mcg/kg	369	± 118

Last Concentration Observed Above the Lower Limit of Quantification (Clast) of Pegenzileukin Secondary · Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

Blood samples were collected at specified timepoints for the assessment of Clast of pegenzileukin. The PK parameters were calculated using non-compartmental method.

Day 1 Cycle 1

Group	Value	95% CI
All Cohorts: Pegenzileukin 24 mcg/kg	17.6	± 13.4

Day 1 Cycle 4

Group	Value	95% CI
All Cohorts: Pegenzileukin 24 mcg/kg	13.0	± 6.11

Time of the Last Concentration Observed Above the Lower Limit of Quantification (Tlast) of Pegenzileukin Secondary · Day 1 Cycle 1 and Day 1 Cycle 4 (each cycle is 21 days)

Blood samples were collected at specified timepoints for the assessment of tlast of pegenzileukin. The PK parameters were calculated using non-compartmental method.

Day 1 Cycle 1

Group	Value	95% CI
All Cohorts: Pegenzileukin 24 mcg/kg	69.45	43.00 – 76.77

Day 1 Cycle 4

Group	Value	95% CI
All Cohorts: Pegenzileukin 24 mcg/kg	68.82	46.28 – 72.58

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs and SAEs were collected from first dose of study treatment administration (Day 1) up to 30 days post last dose of study treatment administration, up to approximately 9 months (Cohorts A, D1 and D2), 26 months (Cohorts B1, B2 and B3) and 21 months (Cohort C). All-cause mortality (deaths) were collected from first dose of study treatment administration (Day 1) to the end of follow-up for death for each participant, up to approximately 19 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy

Serious: 2/5 (40%)

Deaths: 1/5

CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy

Serious: 17/22 (77%)

Deaths: 16/22

CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy

Serious: 13/19 (68%)

Deaths: 15/19

Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy

Serious: 9/18 (50%)

Deaths: 12/18

Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy

Serious: 7/20 (35%)

Deaths: 6/20

Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy

Serious: 19/30 (63%)

Deaths: 24/30

Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy

Serious: 11/24 (46%)

Deaths: 18/24

Serious adverse events (53 terms)

Reaction	System	Cohort A: ESCC Post PD-1/P…	CohortB1:GC/GEJ PD-1/PD-L1…	CohortB2:GC/GEJ PD-1/PD-L1…	Cohort B3: GC/GEJ Post PD-…	Cohort C: HCC Post PD-1/PD…	Cohort D1: CRC Non-MSI-H A…	Cohort D2: CRC Non-MSI-H R…
Disease Progression	General disorders	—	—	—	—	—	—	—
Cytokine Release Syndrome	Immune system disorders	—	—	—	—	—	—	—
Infusion Related Reaction	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Intestinal Obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—
Covid-19	Infections and infestations	—	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—	—
Device Related Infection	Infections and infestations	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—
Pneumonia Pneumococcal	Infections and infestations	—	—	—	—	—	—	—
Respiratory Tract Infection	Infections and infestations	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—
Septic Shock	Infections and infestations	—	—	—	—	—	—	—
Metastases To Bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Failure To Thrive	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Immune Effector Cell-Associated Neurotoxicity Syndrome	Nervous system disorders	—	—	—	—	—	—	—
Radiculopathy	Nervous system disorders	—	—	—	—	—	—	—
Hypovolaemic Shock	Vascular disorders	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—	—	—

Other adverse events (126 terms — click to expand)

Reaction	System	Cohort A: ESCC Post PD-1/P…	CohortB1:GC/GEJ PD-1/PD-L1…	CohortB2:GC/GEJ PD-1/PD-L1…	Cohort B3: GC/GEJ Post PD-…	Cohort C: HCC Post PD-1/PD…	Cohort D1: CRC Non-MSI-H A…	Cohort D2: CRC Non-MSI-H R…
Influenza Like Illness	General disorders	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—
Infusion Related Reaction	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Folliculitis	Infections and infestations	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Oedema Peripheral	General disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Covid-19	Infections and infestations	—	—	—	—	—	—	—
Cytokine Release Syndrome	Immune system disorders	—	—	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—
Dermatitis Acneiform	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Dry Skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Weight Decreased	Investigations	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Abdominal Distension	Gastrointestinal disorders	—	—	—	—	—	—	—
Abdominal Pain Upper	Gastrointestinal disorders	—	—	—	—	—	—	—
Dry Mouth	Gastrointestinal disorders	—	—	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—	—	—
Night Sweats	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—
Urinary Tract Infection	Infections and infestations	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Adrenal Insufficiency	Endocrine disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Disease Progression, Cytokine Release Syndrome, Infusion Related Reaction, Abdominal Pain, Intestinal Obstruction, Covid-19, Cellulitis, Device Related Infection.

Data from ClinicalTrials.gov NCT05104567 adverse events section.

Sponsor's own description

The study is a phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with other anticancer therapies for the treatment of participants aged 18 years and older with advanced and metastatic gastrointestinal cancer. This study is structured as a master protocol for the investigation of SAR444245 with other anticancer therapies.

Sub study 01 - Cohort A aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC).

Sub study 02 - Cohort B1, B2 and B3 would focus on non MSI-H tumors with a large unmet need to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), especially with low PD-L1 expression or after progression on prior PD1/PD-L1-based regimens.

Sub study 03 - Cohort C aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in participants with advanced unresectable or metastatic HCC who relapsed on prior PD1/PD-L1-based regimens.

Sub study 04 - Cohort D1 and D2 aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with either the anti-PD1 antibody pembrolizumab or with the anti-EGFR IgG1 antibody cetuximab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic colorectal cancer (mCRC).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting cytokine and chemokine signaling pathways for cancer therapy.
   Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
2. A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases.
   Raeber ME, Sahin D, Karakus U, Boyman O. · · 2023 · cited 139× · PMID 37004361 · DOI 10.1016/j.ebiom.2023.104539
3. PEGylated therapeutics in the clinic.
   Gao Y, Joshi M, Zhao Z, Mitragotri S. · · 2024 · cited 133× · PMID 38193121 · DOI 10.1002/btm2.10600
4. The application of Interleukin-2 family cytokines in tumor immunotherapy research.
   Zhou Y, Quan G, Liu Y, Shi N, et al · · 2023 · cited 32× · PMID 36936961 · DOI 10.3389/fimmu.2023.1090311
5. Current state of the art: immunotherapy in esophageal cancer and gastroesophageal junction cancer.
   Li N, Sohal D. · · 2023 · cited 22× · PMID 37995002 · DOI 10.1007/s00262-023-03566-5
6. Rethinking Oncologic Treatment Strategies with Interleukin-2.
   Ko B, Takebe N, Andrews O, Makena MR, et al · · 2023 · cited 19× · PMID 37174716 · DOI 10.3390/cells12091316
7. Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy.
   Wolfarth AA, Dhar S, Goon JB, Ezeanya UI, et al · · 2022 · cited 19× · PMID 35291658 · DOI 10.4110/in.2022.22.e5
8. Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma.
   Ooki A, Osumi H, Chin K, Watanabe M, et al · · 2023 · cited 17× · PMID 36872946 · DOI 10.1177/17588359221138377