What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as oxaliplatin-based chemotherapy (e.g., FOLFOX), fluorouracil (FU), leucovorin (LV), capecitabine, and irinotecan, are associated with a range of side effects. Oxaliplatin can cause cumulative sensory neuropathy, which may persist in some patients. Fluorouracil and capecitabine often lead to gastrointestinal issues like diarrhea, nausea, vomiting, and stomatitis, as well as hand-foot syndrome. Irinotecan is known for causing severe neutropenia and diarrhea. Targeted therapies, such as anti-EGFR agents, can result in skin toxicity, including rash and other dermatologic effects. Overall, females tend to experience greater treatment-related toxicity, particularly severe neutropenia.

What prior FDA approvals exist?

Several FDA-approved treatments for colorectal cancer target specific genetic mutations or pathways. Cetuximab and panitumumab are monoclonal antibodies that target the EGFR pathway, used in patients with wild-type KRAS tumors. For patients with BRAF V600E mutations, the combination of encorafenib, binimetinib, and cetuximab is approved. Immunotherapy options include pembrolizumab and nivolumab, which are used for microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancers. These treatments highlight the importance of targeting specific genetic alterations in colorectal cancer.

What other types of research exist?

Promising novel alternatives for colorectal cancer treatment in 2024 include: 1) Futibatinib, an irreversible FGFR1-4 inhibitor, which has shown efficacy in various solid tumors with FGFR aberrations. 2) BTK inhibitors like ibrutinib and acalabrutinib, which are being explored for their potential in solid tumors. 3) Pembrolizumab plus cetuximab, which is under investigation for treatment-refractory cancers and may offer benefits in colorectal cancer with EGFR involvement.

← Back to Search

Protein Tyrosine Phosphatase Inhibitor

SHP2 Inhibitor for Solid Cancers

Phase 1

Recruiting

Led By Ravi Salgia, MD

Research Sponsored by HUYABIO International, LLC.

Eligibility Criteria Checklist

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

Must have

Advanced malignant solid tumors with KRAS or EGFR mutations diagnosed by histology or cytology

Male or female at least 18 years of age at the time of signing the ICF prior to initiation of any study specific activities/procedures

Must not have

Prior treatment with any SHP2 inhibitors

Any unresolved Grade 2 or greater toxicity from previous anti-cancer therapy, except alopecia, within 4 weeks of first study treatment administration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 36 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called HBI-2376 in patients with advanced solid tumors that have specific genetic changes. The drug aims to block a protein that helps cancer cells grow, potentially stopping or slowing down the cancer.

Who is the study for?

Adults with advanced solid tumors that have specific mutations (KRAS or EGFR) and who have not responded to standard treatments can join. They must be able to take pills, have good organ function, and a performance status indicating they are relatively active. People with untreated brain metastases, recent heart issues, ongoing severe side effects from past cancer treatment, pregnancy, or autoimmune diseases cannot participate.

What is being tested?

The trial is testing HBI-2376's safety at different doses in patients with certain genetic mutations in their tumors. It aims to find the highest dose patients can tolerate without severe side effects and will also see how the body processes the drug.

What are the potential side effects?

While specific side effects of HBI-2376 aren't listed here, common ones for cancer drugs include nausea, fatigue, risk of infection due to low blood cell counts, liver problems which might show as yellow skin or eyesight changes.

Eligibility Criteria

Inclusion Criteria

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

Select...

My cancer has KRAS or EGFR mutations.

Select...

I am 18 years or older and have agreed to participate in this study.

Select...

I am fully active or can carry out light work.

Select...

I can take pills and don't have major stomach or intestine issues.

Exclusion Criteria

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

Select...

I have not taken SHP2 inhibitors before.

Select...

I don't have any major side effects from cancer treatment, except for hair loss.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 36 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

To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), of HBI-2376 as an oral monotherapy for advanced solid tumors harboring KRAS or EGFR mutations.

Secondary study objectives

Pharmacokinetic variables including Area Under the Curve (AUC)

Pharmacokinetic variables including clearance

Pharmacokinetic variables including maximum plasma concentration (Cmax)

+3 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Dose Escalation and ExpansionExperimental Treatment1 Intervention

HBI-2376 will be given orally in ascending doses (escalation cohort), until the maximum tolerated dose or recommended Phase 2 dose is reached. Up to 6 patients will then be enrolled in the expansion cohort at the recommended dose.

0 / 6Eligibility 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 colorectal cancer often target specific genetic mutations or pathways involved in tumor growth and survival. For instance, therapies targeting the RAS signal transduction pathway, such as farnesyl transferase inhibitors, aim to inhibit the activation of RAS proteins, which are crucial for cancer cell proliferation. Additionally, agents targeting the epidermal growth factor receptor (EGFR), like cetuximab, are used in patients without RAS mutations to block signals that promote tumor growth. Understanding these mechanisms is vital for colorectal cancer patients as it helps in selecting the most effective treatment based on their tumor's genetic profile, potentially improving outcomes and minimizing unnecessary side effects.

Glufosfamide: can we improve the process of anticancer agent development?