RLY-4008 for Bile Duct Cancer

Not currently recruiting at 58 trial locations

Overseen By Relay Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Elevar Therapeutics

Must not be taking: FGFR inhibitors

Disqualifiers: Active infection, Cardiovascular disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called RLY-4008, an experimental drug, to assess its safety and effectiveness for people with bile duct cancer (cholangiocarcinoma) and other solid tumors. The study will test different doses and examine the treatment's impact on cancer. It targets individuals whose cancer cannot be surgically removed or has spread, and who have specific changes in their FGFR2 gene. Those who have tried other treatments without success or cannot take standard therapies might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering a chance to be among the first to benefit from this new approach.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that RLY-4008 is likely to be safe for humans?

Research has shown that RLY-4008, a new treatment for bile duct cancer, was generally well-tolerated in earlier studies. Patients who received RLY-4008 experienced promising results with manageable side effects. At the tested doses, the treatment shrank tumors without causing major changes in important blood levels, such as phosphate. Additionally, RLY-4008 demonstrated good behavior in the body, with higher doses proving more than 90% effective in targeting the cancer. Overall, these findings suggest that RLY-4008 could be a safe option for people with this type of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

RLY-4008 is unique because it specifically targets FGFR2, a protein often overactive in bile duct cancer. Unlike traditional chemotherapy and targeted therapies that can affect a wide range of cells, RLY-4008 precisely inhibits the FGFR2 pathway, potentially leading to fewer side effects and more effective treatment. Researchers are excited about RLY-4008 because it offers a promising new approach by honing in on a specific genetic alteration associated with this cancer, which could improve outcomes for patients who haven't had success with current treatments.

What evidence suggests that RLY-4008 might be an effective treatment for bile duct cancer?

Research has shown that RLY-4008, the investigational treatment in this trial, holds promise for treating bile duct cancer, particularly in patients with FGFR2 changes. Studies have found that it effectively blocks FGFR2, which is linked to tumor reduction. In patients who had not previously used FGFR inhibitors, there was a strong response against the tumor. Specifically, one study reported an overall response rate of 88%, with some patients experiencing significant tumor shrinkage. This suggests RLY-4008 could be a highly effective option for people with this type of cancer. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced bile duct cancer or other solid tumors that have specific genetic changes in FGFR2. They should be able to perform daily activities with little help (ECOG 0-1) and may have had previous treatments, but not a drug targeting FGFR2. People can't join if they have active infections like HIV/HBV/HCV, serious heart issues, eye problems from similar drugs, poor organ function, or certain electrical heart disturbances.

Inclusion Criteria

Part 3 extension:

I have a solid tumor cancer that is not cholangiocarcinoma.

I have an FGFR2 amplification and haven't been treated with an FGFR inhibitor.

Exclusion Criteria

I have a serious eye problem caused by FGFR inhibitor treatment.

I have a serious heart condition that is not under control.

My brain tumor is getting worse and causing more symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Multiple doses of RLY-4008 for oral administration to determine the appropriate dose

8-12 weeks

Dose Expansion

Participants receive the oral dose of RLY-4008 as determined during Part 1 Dose Escalation

12-16 weeks

Extension

Participants continue to receive the oral dose of RLY-4008 as determined during Part 1 Dose Escalation

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RLY-4008

Trial Overview RLY-4008 is being tested in patients with intrahepatic cholangiocarcinoma (ICC) and other solid tumors that haven't responded well to standard treatments. The study has three parts: finding the right dose of RLY-4008 (dose escalation), seeing how well it works at this dose (dose expansion), and long-term follow-up (extension).

How Is the Trial Designed?

Group I: Part 4: Rollover Experimental Treatment 1 Intervention

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Group II: Part 3: Extension Experimental Treatment 1 Intervention

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Group III: Part 2: Dose Expansion Experimental Treatment 1 Intervention

Oral dose of RLY-4008 as determined during Part 1 Dose Escalation.

Group IV: Part 1: Dose Escalation Experimental Treatment 1 Intervention

Multiple doses of RLY-4008 for oral administration.

Who Is Running the Clinical Trial?

Elevar Therapeutics

Lead Sponsor

Trials

10

Recruited

1,200+

Relay Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

1,900+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4009

Updated dose escalation results for ReFocus, a first-in- ... RLY-4008 had favorable PK with doses ≥40 mg QD providing FGFR2 occupancy ≥90%. 70 mg QD was the RP2D based on PK, safety, anti-tumor activity ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10481131/

RLY-4008, the First Highly Selective FGFR2 Inhibitor with ... These data demonstrate that sustained ∼90% inhibition of pFGFR2 by RLY-4008 is achievable at exposures that are well tolerated.

3. ccanewsonline.com ccanewsonline.com/special-issues/2021-year-in-review-cca/initial-results-of-rly-4008-in-a-first-in-human-study-in-patients-with-fgfr2-altered-cca-and-multiple-solid-tumors

Initial Results of RLY-4008 in a First-in-Human Study in ... Initial efficacy results indicate that RLY-4008 exhibits encouraging antitumor activity in patients with CCA. In 6 patients with FGFR inhibitor–naïve FGFR2 ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)03884-4/fulltext

LBA12 Efficacy of RLY-4008, a highly selective FGFR2 ... Potent efficacy was observed across all doses, particularly at the RP2D with an ORR of 88% (Table). One pt treated at the RP2D had a near-complete response and ...

5. onclive.com onclive.com/view/ongoing-investigation-of-rly-4008-highlights-evolving-treatment-options-for-fgfr2-cholangiocarcinoma

Ongoing Investigation of RLY-4008 Highlights Evolving ... The selective FGFR2 inhibitor RLY-4008 has generated higher response rates compared with historical data for prior pan-FGFR inhibitors in patients with ...

6. onclive.com onclive.com/view/rly-4008-shows-initial-activity-with-a-manageable-safety-profile-in-cholangiocarcinoma

RLY-4008 Shows Initial Activity With a Manageable Safety ... The first highly selective FGFR2 inhibitor RLY-4008 has displayed preliminary efficacy in patients with cholangiocarcinoma and has the ...

7. ir.relaytx.com ir.relaytx.com/news-releases/news-release-details/relay-therapeutics-and-elevar-therapeutics-announce-exclusive

Relay Therapeutics and Elevar Therapeutics Announce ... “Data to-date show that lirafugratinib has the potential to be an important novel medicine for patients with FGFR2-driven cholangiocarcinoma and ...