GIGA-564 for Advanced Cancer

Overseen By James Gulley

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: GigaGen, Inc.

Must not be taking: Systemic steroids

Disqualifiers: Hepatitis B, Hepatitis C, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new drug, GIGA-564 (an anti-CTLA-4 monoclonal antibody), for individuals with advanced solid tumors that have spread or cannot be surgically removed. Researchers will determine the optimal dose for future studies by gradually increasing the dose given to participants. This trial may suit those whose cancer has not responded to standard treatments and who are experiencing measurable disease symptoms. Participants will receive GIGA-564 through an IV every three weeks for up to four cycles. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does allow certain FDA-approved hormonal therapies. If you are on systemic steroids, you need to stop them at least 10 days before enrolling, unless they are for specific conditions like hormone replacement or local treatments.

Is there any evidence suggesting that GIGA-564 is likely to be safe for humans?

Research shows that GIGA-564, a new treatment for advanced cancers, appears safe. Studies have found that GIGA-564 is less toxic than a similar drug, ipilimumab, suggesting patients might experience fewer side effects with GIGA-564.

GIGA-564 specifically targets tumor cells while minimizing impact on other parts of the immune system. This targeted approach is expected to reduce unwanted side effects.

This trial is in its early stages, so researchers are still learning about its safety and tolerability. However, early results are promising, showing less toxicity compared to other treatments in its category. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about GIGA-564 for advanced cancer because it targets cancer cells in a novel way, potentially offering a new hope for patients who have exhausted standard treatments like chemotherapy and immunotherapy. Unlike traditional options, which often attack both healthy and cancerous cells, GIGA-564 is designed to selectively target cancer cells, which could minimize side effects. Additionally, the treatment is administered intravenously, allowing for precise dosage control that can be adjusted to find the most effective amount. This targeted approach could lead to more personalized and effective cancer treatment options.

What evidence suggests that GIGA-564 might be an effective treatment for advanced cancer?

Research has shown that GIGA-564 holds promise in treating advanced cancer. As a monoclonal antibody, it targets specific proteins in the body. GIGA-564 blocks a protein called CTLA-4 on T-cells, which usually helps control the immune system. By blocking CTLA-4, GIGA-564 may enable the immune system to attack cancer more effectively. Early evidence suggests it has better effects against tumors and causes fewer side effects than some existing drugs. This trial will evaluate GIGA-564 in two phases: a dose escalation phase to determine safe dosage levels, and a dose expansion phase to further assess its effectiveness and safety at selected doses. This makes it an exciting option for those considering new cancer treatments. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for people with advanced or widespread solid tumors. Participants must have a tumor that's grown despite treatment, or they can't receive other standard treatments. The exact eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

Life expectancy greater than three months

Willing and able to provide informed consent

Measurable disease on imaging as based on Response Evaluation Criteria in RECIST 1.1

Exclusion Criteria

History of hepatitis B (HBV) infection unless viral load is undetectable

Pregnant or breastfeeding

I have not been treated with therapies targeting CCR8, CD25, or TIGIT.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Phase 1A)

Participants receive GIGA-564 intravenously over at least 60 minutes on Day 1 of every 3 weeks for up to 4 cycles to evaluate up to 5 dose levels

12 weeks

Dose Expansion (Phase 1B)

Participants receive up to 4 cycles of one of up to three tolerable dose levels of GIGA-564 intravenously over at least 60 minutes on Day 1 of every 3 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GIGA-564

Trial Overview The study is testing GIGA-564 to find the highest dose patients can take without serious side effects (MTD) and to decide on the best dose for future studies (RP2D). It's an early-phase trial focusing on safety and dosage levels.

How Is the Trial Designed?

Group I: GIGA-564: Dose Expansion (Phase 1B) Experimental Treatment 1 Intervention

Dose expansion (Phase 1B) of selected dose levels may be initiated following the preliminary clearance of those specified dose levels from the dose escalation (Phase 1A) as determined by the Sponsor and SRC. Participants will receive up to 4 cycles of one of up to three tolerable dose levels of GIGA-564. GIGA-564 will be given intravenously over at least 60 minutes on Day 1 of every 3 weeks (3 weeks = 1 cycle) for up to 4 cycles until time of confirmed disease progression, unacceptable toxicity, or other reason for treatment discontinuation.

Group II: GIGA-564: Dose Escalation (Phase 1A) Experimental Treatment 1 Intervention

Up to 5 dose levels \[0.3, 1.0, 3.0, 10.0, and 20.0 milligrams per kilogram (mg/kg)\] will be evaluated sequentially. Participants will receive GIGA-564 intravenously over at least 60 minutes on Day 1 of every 3 weeks (3 weeks = 1 cycle) for up to 4 cycles until time of confirmed disease progression, unacceptable toxicity, or other reason for treatment discontinuation.

Who Is Running the Clinical Trial?

GigaGen, Inc.

Lead Sponsor

Trials

2

Recruited

60+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The study identified two specific single-chain variable fragment (scFv) antibodies that effectively bind to the CTLA-4 receptor, which is crucial for inhibiting T-cell function in cancer, suggesting their potential use in targeted cancer therapy.

These scFvs were shown to selectively react with the CTLA-4 epitope in laboratory tests, indicating their specificity and potential effectiveness in activating the immune response against tumors by blocking CTLA-4.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production and Evaluation of Specific Single-Chain Antibodies against CTLA-4 for Cancer-Targeted Therapy. Hosseinzadeh, F., Mohammadi, S., Nejatollahi, F.[2022]

Zimberelimab (GLS-010) is a highly effective human monoclonal antibody that binds strongly to the PD-1 receptor, blocking its interaction with PD-L1/2, which is crucial for T cell activation.

In preclinical studies, GLS-010 demonstrated significant anti-tumor effects in mice, indicating its potential as a promising treatment for cancer, warranting further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. Lou, B., Wei, H., Yang, F., et al.[2022]

Monoclonal antibodies targeting CTLA4 enhance T-cell activation, which may lead to a stronger immune response against advanced cancers, showing promise as a novel immunotherapy.

While these anti-CTLA4 mAbs have demonstrated antitumor activity in some patients with manageable side effects, further research is needed to fully understand their mechanisms and validate findings through randomized clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current experience with CTLA4-blocking monoclonal antibodies for the treatment of solid tumors. Agarwala, SS., Ribas, A.[2011]

In a phase II trial involving 47 patients with treatment-refractory colorectal cancer, tremelimumab showed limited efficacy as a single agent, with only one patient (2%) achieving a partial response and 21 patients (45%) surviving for at least 180 days after treatment.

The treatment was associated with some grade 3/4 adverse events, including diarrhea and ulcerative colitis, but these were generally manageable, suggesting that while tremelimumab may not be effective alone, it could be safe for further exploration in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer. Chung, KY., Gore, I., Fong, L., et al.[2022]

In a study of 19 patients with metastatic melanoma treated with the anti-CTLA4 antibody tremelimumab, there was a significant increase in intratumoral infiltration (ITI) by CD8(+) T cells after treatment, with changes ranging from 1-fold to 100-fold in most cases.

Despite the increase in T cell infiltration, there was no significant difference in the characteristics or activation levels of T cells between patients who responded to treatment and those who did not, suggesting that increased T cell presence alone does not guarantee a positive tumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA4 blockade induces frequent tumor infiltration by activated lymphocytes regardless of clinical responses in humans. Huang, RR., Jalil, J., Economou, JS., et al.[2022]

The dual variable domain immunoglobulin (anti-CTLA4 DVD) effectively targets tumors while minimizing immune-related adverse events by preserving beneficial tissue-resident Tregs, as shown in experiments with Rag 1-/- mice.

This innovative approach enhances antitumor efficacy by reducing tumor-infiltrating Tregs and increasing CD8+ T lymphocyte infiltration, demonstrating a mechanism that separates effective cancer treatment from harmful side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity. Pai, CS., Simons, DM., Lu, X., et al.[2020]

Blocking CTLA-4 with anti-CTLA-4 monoclonal antibodies enhances T-cell activation, leading to a stronger immune response against tumors, particularly in metastatic melanoma.

Preliminary studies show that anti-CTLA-4 mAbs are effective and well-tolerated in cancer treatment, with ongoing trials exploring their use in various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA-4: negative regulator of the immune response and a target for cancer therapy. Keilholz, U.[2022]

CTLA4 blocking monoclonal antibodies, specifically ipilimumab and tremelimumab, have shown the ability to induce long-lasting tumor responses in patients with metastatic melanoma, with objective responses observed in 5 to 20% of cases during early clinical trials.

While these treatments can lead to significant and sometimes severe immune-related toxicities, such as colitis and skin rashes, they also demonstrate the potential to break immune tolerance and achieve durable cancer regressions, warranting further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CTLA4 Antibody Clinical Trials in Melanoma. Ribas, A.[2022]

In a phase I trial involving 39 patients with solid tumors, CP-675,206, an anti-CTLA4 monoclonal antibody, was found to be safe at doses up to 15 mg/kg, with dose-limiting toxicities including autoimmune reactions like diarrhea and dermatitis.

The treatment showed promising antitumor activity, particularly in melanoma, with two patients achieving complete responses lasting over 25 months and several others experiencing stable disease or prolonged periods without disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. Ribas, A., Camacho, LH., Lopez-Berestein, G., et al.[2022]

PF-06801591, a monoclonal antibody targeting the PD-1 receptor, was found to be safe and tolerable in a phase 1 trial with 40 patients, showing no dose-limiting toxic effects and manageable adverse events for both intravenous and subcutaneous administration.

The study demonstrated that monthly subcutaneous administration of PF-06801591 is a convenient and effective alternative to intravenous delivery, with an overall objective response rate of 18.4% and full PD-1 receptor occupancy achieved across all dose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Subcutaneous vs Intravenous Administration of Anti-PD-1 Antibody PF-06801591 in Patients With Advanced Solid Tumors: A Phase 1 Dose-Escalation Trial. Johnson, ML., Braiteh, F., Grilley-Olson, JE., et al.[2022]

CTLA-4 blockade, either alone or in combination with PD-1 blockade, effectively activates T cells and shows clinical benefits in melanoma patients, highlighting its role in cancer immunotherapy.

While CTLA-4 blockade has been established as a treatment for melanoma, further research is needed to explore its efficacy in other types of cancer, necessitating well-designed clinical trials that consider immune biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTIA-4 blockade therapy; biology and clinical activity. Tada, K., Heike, Y.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06258304

A Dose Escalation and Expansion Study of GIGA-564 in ... The purpose of this study is to assess the safety and tolerability of GIGA-564 and identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D ...

2. grifols.com grifols.com/en/view-news/-/news/gigagen-presents-ind-enabling-data-and-phase-1-trial-strategy-for-its-novel-anti-ctla-4-oncology-drug-candidate-giga-564-at-sitc-2023

GigaGen Presents IND-Enabling Data and Phase 1 Trial ... Results also show that GIGA-564 offers increased anti-tumor efficacy and reduced toxicity compared to the commercially available drug ...

3. synapse.patsnap.com synapse.patsnap.com/article/gigagen-begins-phase-1-trial-of-giga-564-for-advanced-tumors

GigaGen Begins Phase 1 Trial of GIGA-564 for Advanced ... ... GIGA-564's therapeutic potential. GIGA-564 is a fully human monoclonal antibody that differentiates itself from existing anti-CTLA-4 drugs.

4. gigagen.com gigagen.com/

GigaGen - Antibody Drug Discovery With Single Cell ... Its lead oncology asset, GIGA-564, is a monoclonal antibody that targets CTLA-4, which has demonstrated improved anti-tumor efficacy and reduced toxicity in ...

5. withpower.com withpower.com/trial/phase-1-advanced-or-metastatic-solid-tumor-malignancies-2-2024-4d75a

GIGA-564 for Advanced Cancer GIGA-564 is unique because it is an anti-CTLA-4 monoclonal antibody that works by blocking a protein (CTLA-4) on T-cells, which normally helps keep the immune ...

6. clinicaltrialsarena.com clinicaltrialsarena.com/news/gigagen-solid-tumour-trial/

GigaGen doses first subject in Phase I advanced solid ... A fully human monoclonal antibody, GIGA-564 is designed to minimally block CTLA-4 and selectively deplete intratumoral T regulatory cells ...