Codrituzumab for Solid Tumors

Recruiting at 4 trial locations

Overseen By Michael Ortiz, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: CNS tumor, Uncontrolled seizures, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests codrituzumab, an experimental treatment, to determine its safety and side effects in children and young adults with solid tumors that express the protein GPC3. The researchers aim to understand how the body processes this treatment. This trial suits those whose solid tumors have returned or did not respond to standard treatments and have tested positive for GPC3. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any current anti-cancer therapy or investigational agents to participate.

Is there any evidence suggesting that codrituzumab is likely to be safe for humans?

Research has shown that codrituzumab has been tested in earlier studies, providing information about its safety. In these studies, most patients tolerated codrituzumab well, experiencing no serious side effects.

One study focused on Japanese patients with advanced liver cancer and found codrituzumab to be safe and manageable, with no unexpected or severe side effects reported.

Another study combined codrituzumab with another treatment and observed a strong effect against tumors. While this study focused on efficacy, it also suggested no major safety issues when used with other drugs.

As this is a Phase 1 trial, the primary goal is to ensure the treatment's safety. Researchers are closely monitoring for any side effects. If codrituzumab passes this phase, it is likely safe for further testing in more people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Codrituzumab is unique because it targets a specific protein known as Glypican-3 (GPC3), which is often found on the surface of certain tumor cells, including those in hepatoblastoma. Unlike traditional chemotherapy that attacks rapidly dividing cells indiscriminately, Codrituzumab zeroes in on this protein, potentially leading to more precise treatment with fewer side effects. Researchers are excited about Codrituzumab because its targeted approach could offer a new option for patients with solid tumors that express GPC3, who might not respond well to existing therapies.

What evidence suggests that codrituzumab might be an effective treatment for solid tumors?

Research shows that codrituzumab targets a protein called GPC3, often found on certain solid tumors. In earlier studies, researchers tested codrituzumab in people with liver cancer, but it wasn't very effective at the doses used. Some researchers believe that using higher doses or selecting patients with more GPC3 might lead to better results. Although codrituzumab hasn't shown clear benefits yet, its focus on GPC3 suggests potential usefulness for specific tumors with this protein. This trial will explore these possibilities by testing codrituzumab in different dosing regimens to determine its potential effectiveness. ^{2 4 5 6 7}

Who Is on the Research Team?

Michael Ortiz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to less than 22 years with solid tumors that haven't responded to treatment or have returned after treatment. They must be able to perform daily activities at least half the time, have recovered from previous treatments, not be pregnant, agree to use contraception if of reproductive age, and meet specific blood and organ function criteria.

Inclusion Criteria

Systemic Anticancer Therapy (e.g. Chemotherapy): Not Myelosuppressive: > 7 days must have elapsed from their last dose of anticancer therapy not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts). Myelosuppressive: > 14 days must have elapsed from their last dose of known myelosuppressive anticancer therapy. Antibodies: > 21 days must have elapsed from the infusion of last anticancer antibody. Cellular Therapies: > 42 days must have elapsed from the completion of any type of cellular therapy, including modified T cells, NK cells, dendritic cells, etc.

I had my last radiation treatment more than 14, 42, or 120 days ago, depending on the type and dose.

My neurological condition has been stable for over a week without steroids, and I can use a wheelchair.

Exclusion Criteria

Patients who do not have tumor tissue available for GPC3 testing are not eligible for study entry.

I haven't taken high-dose steroids or immunosuppressants for over 14 days.

Patients with a baseline QTc > 480.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive codrituzumab with a 3+3 dose escalation design to determine the maximum tolerated dose (MTD)

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Codrituzumab

Trial Overview The study tests Codrituzumab's safety and effects in participants with GPC3 protein-expressing solid tumors. It examines how the body absorbs, distributes, and eliminates this drug. The goal is to find a safe dosage that causes few or mild side effects.

How Is the Trial Designed?

Group I: Codrituzumab Experimental Treatment 1 Intervention

For Phase A of the study, we will use the 3+3 study design, with 2 planned dose levels, starting at 50% of the adult RP2D to confirm the pediatric RP2D/MTD. 6-9,43 Phase B will include an expansion cohort for patients with hepatoblastoma.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Chugai Pharma USA

Industry Sponsor

Trials

9

Recruited

4,600+

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168827816301064

Randomized phase II placebo controlled study of ... In this clinical trial, codrituzumab was not found be effective against liver cancer. It was suggested though that a higher dose of codrituzumab or ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01507168

NCT01507168 | A Study of GC33 (RO5137382) in Patients ... This randomized, placebo-controlled, multicenter study will evaluate the efficacy and safety of GC33 (RO5137382) in previously treated patients.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27085251/

Randomized phase II placebo controlled study of ... It was suggested though that a higher dose of codrituzumab or selecting patients with high level of glypican-3 or its mediator CD16 might improve outcome.

4. aacrjournals.org aacrjournals.org/clincancerres/article/19/4/920/78147/First-in-Man-Phase-I-Study-of-GC33-a-Novel

First-in-Man Phase I Study of GC33, a Novel Recombinant ... Tumor response was assessed every 8 weeks using Response Evaluation Criteria in Solid Tumors criteria. Results: Twenty patients were enrolled and treated with ...

5. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(16)30106-4/abstract

Randomized phase II placebo controlled study ... Codrituzumab did not show clinical benefit in this previously treated HCC population. Whether higher codrituzumab drug exposure or the use of CD16 and GPC3 as ...

6. medchemexpress.com medchemexpress.com/codrituzumab.html?srsltid=AfmBOoocSXAhL0vy4ppKYD6if1LEt0wodkuH3FvhWBoq1OadNe4knwvm

Codrituzumab (GC33) | Anti-GPC3 Antibody Codrituzumab (once-weekly for 21 days) combined with PD-L1 mAb demonstrates a marked antitumor effect, enhancing tumor infiltration of PD-L1-positive immune ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4317809/

Japanese phase I study of GC33, a humanized antibody ... This study aimed to assess the safety, tolerability, and pharmacokinetic characteristics of GC33 in Japanese patients with advanced hepatocellular carcinoma.