What side effects are associated with this type of intervention?

Common treatments for metastatic cancer that are similar to THOR-707 include immunotherapy agents like nivolumab, ipilimumab, and pembrolizumab. Known side effects of these treatments often include immune-related adverse events such as colitis, dermatitis, hepatitis, and endocrinopathies. Other common side effects are fatigue, rash, pruritus, diarrhea, and pneumonitis. Severe adverse events can include grade 3 or 4 toxicities like severe diarrhea, infusion-related reactions, and pneumonia. These side effects result from the enhanced immune response triggered by these therapies.

What prior FDA approvals exist?

The FDA has approved several immunotherapy agents for the treatment of metastatic cancers, similar to THOR-707, which is designed to enhance the immune response against tumors. High-dose interleukin-2 (IL-2) has been approved for metastatic melanoma and renal cell carcinoma. Pembrolizumab and nivolumab, both PD-1 inhibitors, are approved for metastatic melanoma, non-small cell lung cancer, and other cancers. Ipilimumab, a CTLA-4 inhibitor, is also approved for metastatic melanoma. These treatments work by modulating the immune system to better target and destroy cancer cells.

What other types of research exist?

Promising novel alternatives to THOR-707 for metastasis patients include: 1) Pembrolizumab (Keytruda) combined with chemotherapy, which has shown efficacy in non-small cell lung cancer. 2) Avelumab, a PD-L1 inhibitor, which has demonstrated durable responses in mesothelioma. 3) Nivolumab combined with Ipilimumab, which has been effective in renal cell carcinoma. 4) Enfortumab Vedotin, an antibody-drug conjugate, which has shown promise in urothelial carcinoma. These agents represent advanced immunotherapy options that enhance the body's immune response against tumors.

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Cytokine

THOR-707 Combination Therapy for Cancer (HAMMER Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Synthorx, Inc, a Sanofi company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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: 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.

Must not have

Known hypersensitivity or contraindications to any components of THOR-707, PEG, pegylated drugs, and E. coli derived-protein, checkpoint inhibitor, or anti-EGFR antibody for applicable cohorts.

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.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up study day 1 up to day 42 (6 week-cycle)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called THOR-707 to see if it is safe and effective for cancer patients. The drug aims to help the immune system fight cancer. The study will check how well the drug works alone and with other treatments.

Who is the study for?

Adults with advanced or metastatic solid tumors who have tried standard treatments without success, are intolerant to them, or have no other effective options available. Participants should not have received certain cancer therapies recently and must be free of specific health conditions like uncontrolled diabetes or active infections. They need functioning major organs, measurable disease per RECIST v1.1 criteria, a life expectancy over 12 weeks, and an ECOG status of 0-1.

What is being tested?

The trial is testing THOR-707 alone and in combination with an anti-EGFR antibody or checkpoint inhibitor for safety and maximum tolerated dose (MTD). It also aims to observe the preliminary effectiveness by measuring tumor response rates, time to response, duration of response, progression-free survival (PFS), overall survival (OS), and disease control rate.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation in various organs which could manifest as flu-like symptoms; skin reactions; digestive issues; changes in liver function tests; fatigue; potential infusion-related reactions; and possibly others depending on individual patient responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My advanced cancer has been confirmed by lab tests and has at least one tumor that can be safely biopsied.

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My cancer type is approved for anti-PD(L)1 treatment.

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I am fully active or can carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not allergic to THOR-707, PEG, pegylated drugs, E. coli proteins, checkpoint inhibitors, or anti-EGFR antibodies.

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I haven't had major surgery in the last 30 days or still recovering from one.

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I haven't had serious heart problems or surgeries in the last 6 months.

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I have an autoimmune disease that needed treatment in the last 3 months.

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I have HIV or active hepatitis C.

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I had a severe reaction to previous immune therapy.

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I have a specific type of melanoma in my eye or related to my eye.

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I have not had serious bleeding in the last 2 weeks.

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I have had serious lung problems in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ study day 1 up to day 42 (6 week-cycle)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~study day 1 up to day 42 (6 week-cycle)

This trial's timeline: 3 weeks for screening, Varies for treatment, and study day 1 up to day 42 (6 week-cycle) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD)- Cohort G

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

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

+5 more

Secondary study objectives

Clinical Benefit Rate (CBR)

Disease Control Rate (DCR) according to RECIST version 1.1

Duration of Response (DOR) according to RECIST version 1.1

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Group I: Cohort H Monotherapy QW/Q2W (Dose Expansion)Experimental Treatment1 Intervention

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.

Group II: Cohort G Monotherapy QW/Q2W (Dose Escalation)Experimental Treatment1 Intervention

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.

Group III: Cohort F-THOR-707 Q3W with checkpoint inhibitor (Dose Expansion)Experimental Treatment2 Interventions

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.

Group IV: Cohort E-THOR-707 Q2W with checkpoint inhibitor (Dose Expansion)Experimental Treatment2 Interventions

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.

Group V: Cohort D-THOR-707 Q3W with anti-EGFR antibody (Dose Escalation)Experimental Treatment2 Interventions

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.

Group VI: Cohort C-THOR-707 Q3W with checkpoint inhibitor (Dose Escalation)Experimental Treatment2 Interventions

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.

Group VII: Cohort B-THOR-707 Q3W Monotherapy (Dose Escalation)Experimental Treatment1 Intervention

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.

Group VIII: Cohort A-THOR-707 Q2W Monotherapy (Dose Escalation)Experimental Treatment1 Intervention

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.

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immunotherapy agents such as THOR-707, ipilimumab, nivolumab, and interleukin-2 work by enhancing the body's immune response to target and destroy cancer cells. THOR-707 is designed to increase the activity of CD8+ T cells and natural killer cells within the tumor microenvironment, making it more hostile to cancer cells. Ipilimumab blocks CTLA-4, a protein that downregulates the immune system, thereby boosting T-cell activity. Nivolumab inhibits PD-1, a checkpoint protein on T cells, preventing cancer cells from evading immune detection. Interleukin-2 stimulates the growth and activity of T cells and natural killer cells. These mechanisms are crucial for metastasis patients as they help the immune system recognize and attack metastatic tumors, potentially leading to better control of the disease and improved survival outcomes.

Characteristics and management of immunerelated adverse effects associated with ipilimumab, a new immunotherapy for metastatic melanoma.