What side effects are associated with this type of intervention?

Common side effects of treatments similar to Dazostinag, which include immune-modulating therapies and direct tumor cell targeting agents, often involve fatigue, rash, diarrhea, and immune-related adverse events such as pneumonitis, colitis, hepatitis, and endocrinopathies. Targeted therapies like BRAF and MEK inhibitors can cause skin toxicities, fever, fatigue, and cardiovascular issues. These treatments aim to enhance the immune response against tumors or directly inhibit tumor cell growth, but they come with a risk of significant side effects that require careful management.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of tumors that work through immune modulation or direct tumor cell targeting. Pembrolizumab, an anti-PD-1 antibody, has been approved for various cancers, including melanoma and non-small cell lung cancer, due to its ability to enhance the immune system's response against tumor cells. Ipilimumab, an anti-CTLA-4 antibody, is another immune checkpoint inhibitor approved for melanoma. Nivolumab, also an anti-PD-1 antibody, has been approved for melanoma, lung cancer, and other tumors. Additionally, combination therapies such as pembrolizumab with chemotherapy or other targeted agents like lenvatinib have shown efficacy in treating advanced cancers. These treatments share similarities with Dazostinag, which is being studied for its potential anti-tumor effects, possibly through immune modulation or direct targeting of tumor cells.

What other types of research exist?

Promising novel alternatives to Dazostinag for tumor patients in 2024 include Pembrolizumab, Nivolumab, Ipilimumab, and combination therapies such as Pembrolizumab with chemotherapy or Nivolumab with Ipilimumab. These treatments have demonstrated potential anti-tumor effects through immune modulation and direct tumor cell targeting in various cancers.

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Monoclonal Antibodies

TAK-676 + Pembrolizumab for Metastatic Cancer (iintune-1 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Takeda

Eligibility Criteria Checklist

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

Must have

CRC (Part 3): Third-line or later MSI-H/dMMR CRC (Part 3A): histologically confirmed recurrent locally advanced or metastatic MSI-H/dMMR CRC with disease progression on or following therapy with anti-PD-1 or PD-L1 antibody and at least one line of combination chemotherapy, Third-line MSS/pMMR CRC (Part 3B): histologically confirmed recurrent locally advanced or metastatic MSS/pMMR CRC with disease progression on or following therapy with 2 different lines of combination chemotherapy, MSI/MMR status confirmed by a clinically-approved IHC and/or PCR assay, treated with 2 prior lines of therapy in the recurrent locally advanced or metastatic setting

TAK-676 SA (dose escalation Part 1A): histologically confirmed advanced or metastatic solid tumors with no standard therapeutic options or intolerant to these therapies

Must not have

For participants receiving pembrolizumab only: contraindication and/or intolerance to the administration of pembrolizumab

History of brain metastasis unless clinically stable (>=6 weeks) after prior surgery, whole-brain radiation, or stereotactic radiosurgery, and off corticosteroids

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 54 months

Awards & highlights

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial is testing a new drug called dazostinag, alone and with another drug called pembrolizumab, to treat people with advanced solid tumors. It focuses on patients with specific types of head and neck cancer and colorectal cancer who have few other treatment options. The goal is to find a safe dose and see if the combination can help the immune system fight the cancer more effectively.

Who is the study for?

Adults with advanced or metastatic solid tumors who haven't responded to standard treatments, or can't tolerate them, may join this trial. They should be in good physical condition (ECOG 0-1), have not received certain vaccines recently, and must not have active hepatitis or heart issues. Smokers and those with specific lung conditions cannot participate.

What is being tested?

The study is testing TAK-676 alone and combined with Pembrolizumab to find the highest dose patients can take without severe side effects. It includes a phase where doses increase (dose escalation) followed by a phase that tests the chosen dose more broadly (dose expansion). Some will also receive chemotherapy drugs like Platinum and 5-fluorouracil.

What are the potential side effects?

Possible side effects of TAK-676 include reactions at the infusion site, fatigue, digestive problems, blood disorders, increased risk of infections, and potential organ inflammation. Pembrolizumab might cause immune-related adverse effects such as skin rash or thyroid dysfunction.

Eligibility Criteria

Inclusion Criteria

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

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I have advanced cancer with no standard treatment options left or cannot tolerate them.

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I can carry out all my daily activities without help.

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My cancer is advanced or has spread, and standard treatments haven't worked or can't be used.

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My cancer did not respond to previous immunotherapy treatments.

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My advanced cancer has no standard treatment options left, or I can't tolerate them.

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I am fully active or can carry out light work.

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My tumor has not been treated with anti-PD-1 or anti-PD-L1 therapy.

Exclusion Criteria

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

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I cannot take pembrolizumab due to adverse reactions or medical reasons.

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My brain metastasis has been stable for over 6 weeks, and I'm not on corticosteroids.

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I do not have severe lung problems or uncontrolled fluid in my lungs or abdomen.

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I have experienced moderate to severe low blood pressure.

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I cannot tolerate or am allergic to platinum-based chemotherapy and 5-FU.

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I have ongoing, active hepatitis.

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I currently have a serious infection or a high fever due to cancer.

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I have refused all standard treatments available.

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I am not taking drugs that affect liver transport proteins.

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I have received a stem cell or organ transplant.

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I am not on any cancer treatment except hormone therapy for breast cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 54 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 54 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 54 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity

Number of Participants with Dose-Limiting Toxicities (DLTs)

Secondary study objectives

Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Disease Control Rate (DCR)

Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Duration of Response (DOR)

Dose Escalation, Japan Safety Lead-in, and Expansion Phases: Overall Response Rate (ORR)

+5 more

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

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: Part 3B (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSS/pMMR CRCExperimental Treatment2 Interventions

Dazostinag 5.0 mg, infusion, IV, will be administered in participants with microsatellite stable/mismatch repair proficient (MSS/pMMR) CRC at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. along with pembrolizumab 200 mg infusion, IV, Q3W.

Group II: Part 3A (Expansion Phase in CRC): Dazostinag + Pembrolizumab in MSI-H/dMMR CRCExperimental Treatment2 Interventions

Dazostinag 5.0 mg, infusion, IV, will be administered in participants with microsatellite instability-high /mismatch repair deficient (MSI-H/dMMR) colorectal cancer (CRC) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W.

Group III: Part 2B (SCCHN Dose Expansion Phase): Dazostinag + Pembrolizumab + ChemotherapyExperimental Treatment4 Interventions

Dazostinag 5.0 mg, infusion, IV, will be administered in participants with SCCHN at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle. Pembrolizumab infusion, IV will be administered at 200 mg Q3W. Platinum-based chemotherapy comprising the combination of carboplatin (target area under the curve of 5 milligrams per milli Liters per minute (mg/mL/minute) \[AUC 5\]) or cisplatin (100 milligrams per square meter \[mg/m\^2\] Day 1 of each treatment cycle), and 5-fluorouracil (\[5-FU\]; 1000 mg/m\^2 per day for 4 consecutive days) Q3W for up to 6 cycles.

Group IV: Part 2A (SCCHN CPS ≥ 1 Dose Expansion and Optimization Phase): Dazostinag + PembrolizumabExperimental Treatment2 Interventions

Dazostinag 5.0 mg, infusion, IV, will be administered in participants with squamous cell carcinoma of head and neck (SCCHN) at the identified dose level from Part 1 on Days 1, 8, and 15 in a 21-day cycle along with pembrolizumab 200 mg infusion, IV, Q3W. Dose optimization may be performed in this phase.

Group V: Part 1B (Combination Dose Escalation Phase): Dazostinag + PembrolizumabExperimental Treatment2 Interventions

Dazostinag escalating doses (0.2 mg and above) in combination with pembrolizumab 200 mg, infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycle. Pembrolizumab 200 mg will be administered 1 hour prior to Dazostinag once every 3 weeks (Q3W). The dosing will be initiated when at least two dose levels (DLs) of Part 1A have been evaluated.

Group VI: Part 1 (Monotherapy Dose Escalation Phase): Dazostinag Safety Lead-in + Dazostinag SA [Part 1A]Experimental Treatment1 Intervention

Safety Lead-in: Dazostinag 0.1 mg, infusion, intravenously (IV), once weekly, on Days 1, 8 and 15 in 21-day treatment cycles. Dazostinag SA Dose Escalation (Part 1A): Dazostinag single agent (SA), infusion, IV, once weekly on Days 1, 8 and 15 in each 21-day treatment cycles with escalating doses (0.2 mg and above). The dosing will be initiated in the Dazostinag SA Dose Escalation Phase based on the available safety and tolerability data from the Safety Lead-in.

Group VII: Arm B: Japan Safety Lead-in Dazostinag Transitioned to PembrolizumabExperimental Treatment2 Interventions

Dazostinag 5.0 mg, infusion, IV, as an SA once on Day 1 in Cycle 0 (cycle length=7 days) in Japanese participants with advanced or metastatic solid tumors based on confirmation of tolerability in Arm A. Following Cycle 0 (7 days), participants will be transitioned to the same dose level of dazostinag on Days 1, 8, and 15 of each 21-day cycle in combination with pembrolizumab administered Q3W, IV, on Day 1 in each 21-day cycle. Additional dose levels of dazostinag (such as ≥ 7.0 mg) in combination with pembrolizumab (200 mg, Q3W) may be explored in the Safety Lead-in.

Group VIII: Arm A: Japan Safety Lead-in Dazostinag + PembrolizumabExperimental Treatment2 Interventions

Dazostinag 5.0 mg, infusion, IV, in Japanese participants with advanced or metastatic solid tumors on Days 1, 8, and 15 in each 21-day cycle in combination with pembrolizumab 200 mg administered Q3W, IV, on Day 1 in each 21-day cycle. Additional dose levels of Dazostinag (such as 14.0 mg) in combination with pembrolizumab (200 mg, Q3W) may be explored in the Safety Lead-in.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Platinum

Not yet FDA approved

Fluorouracil

FDA approved

0 / 19Eligibility 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

Common treatments for tumors often involve immune modulation and direct targeting of tumor cells. Immune checkpoint inhibitors, such as pembrolizumab, work by blocking proteins like PD-1 on immune cells, thereby enhancing the body's immune response against tumor cells. This is crucial for patients as it helps the immune system recognize and destroy cancer cells more effectively. Additionally, targeted therapies like tyrosine kinase inhibitors disrupt specific pathways that tumors use for growth and survival, directly inhibiting tumor cell proliferation. These mechanisms are significant for tumor patients as they offer more precise and potentially less toxic treatment options compared to traditional chemotherapy.