A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors (THOR-707-101)

NCT04009681 | Terminated Phase 1 FDA Drug

• 3 other identifiers: THOR-707-101 (TCD16843)U1111-1298-72812023-508422-95-00
• Study Type: interventional
• Target: 175
• Locations: 6 countries
• Sites: 24

Brief Summary

Primary Objectives:

• Evaluate the safety and tolerability of THOR-707 as a single agent and as a combination therapy (identify Dose Limiting Toxcitiy (DLTs) in Cohorts A, B, C, D, and G, and adverse events (AEs)/serious adverse event (SAE) profile in Cohorts A, B, C, D, E, F, and G)
• Define the Maximium Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D) of THOR-707 as a single agent and as a combination therapy (Cohorts A, B, C, D, and G)
• Evaluate preliminary anti-tumor activity of THOR-707 as a single agent by determination of the objective response rate (ORR) defined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Cohort H only) Secondary Objectives:
• Evaluate preliminary anti-tumor activity of THOR-707 as a single agent and as a combination therapy by determination of the objective response rate (ORR) defined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Cohorts A, B, C, D, E, F, and G)
• Determine time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and clinical benefit rate (CBR) of THOR-707 as a single agent and as a combination therapy
• Evaluate the safety and tolerability of THOR-707 monotherapy QW/Q2W (AE/serious adverse event \[SAE\] profile) (Cohort H only).

Conditions

Metastasis

Keywords

Synthorx; THOR-707; THOR 707; Interleukin 2; Interleukin-2; IL2; oncology; immuno-oncology; immunotherapy; IL-2; SAR444245; Sanofi

Outcome Measures

Primary Outcomes (8)

• Rate of Dose-Limiting Toxicities (DLTs)- Cohorts A, B, C, and D

  Based on toxicities observed

  Study Day 1 up to Day 29

• Maximum Tolerated Dose (MTD)- Cohorts A, B, C, and D

  Based on toxicities observed

  Study Day 1 up to Day 29

• Recommended Phase 2 Dose (RP2D)- Cohorts A, B, C, and D

  Based on toxicities observed

  Study Day 1 up to Day 29

• Number of participants with treatment emergent adverse events, serious adverse events, and laboratory abnormalities - Cohorts A, B, C, D, E, F, and G

  Safety will be assessed by monitoring adverse events, clinical laboratory evaluations, vital signs, and ECG parameters.

  Study Day 1 up to approximately 24 months

• Rate of Dose-Limiting Toxicities (DLTs) -Cohort G

  Based on toxicities observed

  Study Day 1 up to Day 42 (6 week-cycle)

• Recommended Phase 2 Dose (RP2D) of THOR-707- Cohort G

  Based on toxicities observed

  Study Day 1 up to Day 42 (6 week-cycle)

• Maximum Tolerated Dose (MTD)- Cohort G

  Based on toxicities observed

  Study Day 1 up to Day 42 (6 week-cycle)

• Objective Response Rate (ORR) according to RECIST version 1.1 -Cohort H

  ORR, defined as the proportion of subjects with confirmed complete response (CR) or partial response (PR); a confirmed response is a response that persists on repeat-imaging ≥4 weeks after initial documentation of response.

  Study Day 1 up to approximately 24 months

Secondary Outcomes (8)

• Objective Response Rate (ORR) according to RECIST version 1.1 Cohort A, B, C, D, E, F, and G)

  Study Day 1 up to approximately 24 months

• Duration of Response (DOR) according to RECIST version 1.1

  Study Day 1 up to approximately 24 months

• Progression-Free Survival (PFS) according to RECIST version 1.1

  Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to approximately 24 months

• Overall Survival according to RECIST version 1.1

  Study Day 1 up to time of death, assessed up to approximately 24 months

• Time to Response (TTR) according to RECIST version 1.1

  Study Day 1 up to approximately 24 months

Study Arms (8)

Cohort A-THOR-707 Q2W Monotherapy (Dose Escalation)

EXPERIMENTAL

Subjects with advanced or metastatic solid tumors will receive THOR-707 in sequential ascending doses as a monotherapy via intravenous (IV) administration every 2 weeks (Q2W) until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: THOR-707

Cohort B-THOR-707 Q3W Monotherapy (Dose Escalation)

EXPERIMENTAL

Subjects with advanced or metastatic solid tumors will receive THOR-707 in sequential ascending doses as a monotherapy via IV administration every 3 weeks (Q3W) until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: THOR-707

Cohort C-THOR-707 Q3W with checkpoint inhibitor (Dose Escalation)

EXPERIMENTAL

Subjects with advanced or metastatic solid tumors will receive THOR-707 Q3W in sequential ascending doses in combination with a checkpoint inhibitor Q3W or every 6 weeks (Q6W) via IV administration until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: THOR-707; Drug: Checkpoint inhibitor

Cohort D-THOR-707 Q3W with anti-EGFR antibody (Dose Escalation)

EXPERIMENTAL

Subjects with advanced or metastatic solid tumors will receive THOR-707 Q3W in sequential ascending doses in combination with an anti-EGFR antibody weekly dosing (QW) via IV administration until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: THOR-707; Drug: anti-EGFR antibody

Cohort E-THOR-707 Q2W with checkpoint inhibitor (Dose Expansion)

EXPERIMENTAL

Subjects with advanced or metastatic solid tumors will receiveTHOR-707 Q2W at recommended Phase 2 dose (RP2D) with a checkpoint inhibitor via IV administration Q6W; it will consist of one 8-week cycle of THOR-707 monotherapy on Cycle 1 Day 1 followed by THOR-707 Q2W + checkpoint inhibitor Q6W starting at Cycle 1 Day 15. Subsequently treatment will consist of repeated 6-week cycles with combination therapy.

Drug: THOR-707; Drug: Checkpoint inhibitor

Cohort F-THOR-707 Q3W with checkpoint inhibitor (Dose Expansion)

EXPERIMENTAL

Subjects with advanced or metastatic solid tumors will receive THOR-707 Q3W at recommended Phase 2 dose (RP2D) with a checkpoint inhibitor via IV administration Q6W will consist of one 9-week cycle of THOR monotherapy on Cycle 1 Day 1 followed by THOR-707 Q3W + checkpoint inhibitor at Cycle 1 Day 22. Subsequently treatment will consist of repeated 6-weeks cycles with combination therapy.

Drug: THOR-707; Drug: Checkpoint inhibitor

Cohort G Monotherapy QW/Q2W (Dose Escalation)

EXPERIMENTAL

Subjects with advanced or metastatic solid tumors will receive THOR707 monotherapy QW for 6 weeks (induction period), and then every Q2W (maintenance period), which is referred as QW/Q2W thereafter, until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: THOR-707

Cohort H Monotherapy QW/Q2W (Dose Expansion)

EXPERIMENTAL

Subjects with late-line metastatic melanoma will receive THOR707 monotherapy at RP2D for Cohort G. Cycle 1 will consist of THOR-707 QW for 6 weeks; Cycle 2 and beyond will consist of THOR-707 Q2W.

Drug: THOR-707

Interventions

THOR-707 DRUG

Pharmaceutical form: solution for intravenous (IV) administration; Route of administration: IV administration

Also known as: SAR444245, Pegenzileukin

Cohort A-THOR-707 Q2W Monotherapy (Dose Escalation); Cohort B-THOR-707 Q3W Monotherapy (Dose Escalation); Cohort C-THOR-707 Q3W with checkpoint inhibitor (Dose Escalation); Cohort D-THOR-707 Q3W with anti-EGFR antibody (Dose Escalation); Cohort E-THOR-707 Q2W with checkpoint inhibitor (Dose Expansion); Cohort F-THOR-707 Q3W with checkpoint inhibitor (Dose Expansion); Cohort G Monotherapy QW/Q2W (Dose Escalation); Cohort H Monotherapy QW/Q2W (Dose Expansion)

Checkpoint inhibitor DRUG

Pharmaceutical form: solution for IV administration; Route of administration: IV administration

Also known as: pembrolizumab

Cohort C-THOR-707 Q3W with checkpoint inhibitor (Dose Escalation); Cohort E-THOR-707 Q2W with checkpoint inhibitor (Dose Expansion); Cohort F-THOR-707 Q3W with checkpoint inhibitor (Dose Expansion)

anti-EGFR antibody DRUG

Pharmaceutical form: solution for IV administration; Route of administration: IV administration

Also known as: cetuximab

Cohort D-THOR-707 Q3W with anti-EGFR antibody (Dose Escalation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable disease per RECIST v1.1. For Cohort G participants must have at least 1 measurable lesion, and for Part 3 (Cohorts E, F and H) participants must have at least 2 measurable lesions to safely perform mandatory pre \& on-treatment biopsy.
• Life expectancy greater than or equal to 12 weeks.
• For Part 2 exclusively: While it is highly preferred to enroll subjects who are naïve to PD-1 inhibitors into a Part 2 dose escalation cohort, this is not an enrollment requirement. However, subjects who enroll into a Part 2 safety expansion cohort must be naïve to PD-1 inhibitors. If such subject is unable to meet this requirement but otherwise remains a good candidate for study enrollment, the Investigator should discuss with the Sponsor whether the subject may be enrolled.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate cardiovascular, hematological, liver, and renal function.
• Histologically or cytologically confirmed diagnosis of advanced and/or metastatic solid tumors with at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the Investigator.
• Caution: Cohort D only patients with KRAS mutant colon cancer have not typically benefitted from the addition of cetuximab in earlier lines of therapy.
• Caution: Cohorts E \& F enrollment will include only patients with tumors for which anti-PD(L)1 as single agent or in combination treatments are approved.
• Caution: For Cohort H, the participant must have received at least one prior line of therapy for metastatic melanoma and/or does not have any standard of care (SoC) treatment option or participant declines or is intolerant to be treated with SoC treatment.
• Subjects with advanced or metastatic solid tumors who have refused SoC; or for whom no reasonable SoC exists that would confer clinical benefit; or for whom standard therapy is intolerable, not effective, or not accessible.
• Prior anti-cancer therapy is allowed as long as any treatment related toxicity is resolved to an appropriate level.
• Females of childbearing potential and men who are not surgically sterile must agree to use medically-accepted method of birth control during the study and for at least7 days (for Cohorts A, B, G and H), at least 2 months (for Cohort D), or at least 4 months (for Cohorts C, E and F) for females, and for at least 3 days for males \[corresponding to the time needed to eliminate study intervention\] after the last dose of study intervention.
• \[Females\] Negative serum pregnancy test within 7 days prior to initiating study treatment in premenopausal women and women less than 12 months after menopause.
• \[Males\] Agreement to refrain from donating or banking sperm during the treatment period and for at least 3 days after last dose of study treatment.
• In Spain, Chile, and Argentina: Only cohorts G and H will be open to enrollment.

You may not qualify if:

• Radiotherapy ≤ 14 days prior to first dose of study drug (palliative radiation or stereotactic radiosurgery within 7 days prior to start of study treatment).
• Treated with systemic anti-cancer therapy or an investigational agent within 2 weeks prior to start of study drug treatment (within 4 weeks for immunotherapy and tyrosine kinase inhibitor therapy).
• Subjects who experienced Grade 3 or higher immune-related toxicity from prior immuno-oncology therapy.
• Major surgery ≤ 30 days prior to first dose of study drug, or has not recovered to at least Grade 1 from adverse effects from such procedure, or anticipation of the need for major surgery during study treatment.
• Active autoimmune disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
• Primary central nervous system (CNS) disease or leptomeningeal disease; known CNS metastases unless treated, are asymptomatic, are without evidence of radiological progression for at least 8 weeks, and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days prior to Screening.
• Abnormal pulmonary function within the previous 6 months, including pneumonitis, active pneumonitis, interstitial lung disease requiring the use of steroids, idiopathic pulmonary fibrosis, confirmed pleural effusion, severe dyspnea at rest or requiring supplementary oxygen therapy.
• Parenteral antibiotics within 14 days of the first dose of study drug.
• History of allogenic or solid organ transplant.
• Uncontrolled diabetes mellitus or other uncontrolled immune-related endocrinopathies in the opinion of the Investigator.
• Known human immunodeficiency virus (HIV) infection or active infection with hepatitis C.
• For known uncontrolled hepatitis B virus (HBV) infection:
• i. Anti-HBV therapy started before initiation of IMP and HBV viral load \<2000 IU/mL (104 copies/mL) are eligible. The anti-HBV therapy should continue throughout the treatment period. ii. Positive anti-HBc, positive anti HBs, negative HBsAg, and HBV virus load without HBV therapy are eligible.
• Received a live-virus vaccination ≤14 days prior to first dose of study drug. Seasonal flu and other inactivated vaccines that do not contain live virus are permitted.
• Clinically significant bleeding within 2 weeks prior to initial THOR-707 dose (e.g., gastrointestinal bleeding, intracranial hemorrhage).

Sponsors & Collaborators

• Synthorx, Inc, a Sanofi company: lead

Study Sites (24)

Investigational Site Number-1008

Scottsdale, Arizona, 85250, United States

Location

Investigational Site Number-1005

Denver, Colorado, 80218, United States

Location

Investigational Site Number-1004

Sarasota, Florida, 34232, United States

Location

Investigational Site Number-1003

Nashville, Tennessee, 37203, United States

Location

Investigational Site Number-1007

Dallas, Texas, 75032, United States

Location

Investigational Site Number-1002

Houston, Texas, 77030, United States

Location

Investigational Site Number-1001

San Antonio, Texas, 78229, United States

Location

Investigational Site Number-7002

Buenos Aires, Argentina

Location

Investigational Site Number-2004

New South Whales, Australia

Location

Investigational Site Number-2001

Perth, Australia

Location

Investigational Site Number-2002

Victoria, Australia

Location

Investigational Site Number-2003

Victoria, Australia

Location

Investigational Site Number- 6001

Santiago, Chile

Location

Investigational Site Number-6002

Santiago, Chile

Location

Investigational Site Number-4002

Singapore, Singapore

Location

Investigational Site-4001

Singapore, Singapore

Location

Investigational Site Number-5001

Barcelona, Spain

Location

Investigational Site Number-5006

Barcelona, Spain

Location

Investigational Site Number-5007

Barcelona, Spain

Location

Investigational Site Number-5002

Madrid, Spain

Location

Investigational Site Number-5003

Madrid, Spain

Location

Investigational Site Number-5004

Madrid, Spain

Location

Investigational Site Number-5005

Madrid, Spain

Location

Investigational Site Number-5105

Madrid, Spain

Location

Related Links

• TCD16843 Plain Language Results Summary

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

pembrolizumab; Cetuximab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 5, 2019
• Study Start: June 20, 2019
• Primary Completion: December 2, 2025
• Study Completion: December 2, 2025
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

AR (1); CL (2); SG (2); US (7); AU (4); ES (8)