GB1211 + Pembrolizumab for Melanoma and Head & Neck Cancer

Overseen By Chris Fountain, RN, ONC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Providence Health & Services

Must not be taking: Galectin antagonists, Steroids

Disqualifiers: Autoimmune disease, Brain metastases, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 63 weeks

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new combination of treatments, GB1211 (also known as Selvigaltin) and pembrolizumab, for individuals with advanced melanoma or head and neck cancer. The primary goal is to determine if this combination outperforms pembrolizumab alone. Suitable candidates include those with melanoma that cannot be surgically removed or those with head and neck cancer that has recurred or spread, particularly if previous treatments like chemotherapy have failed. As a Phase 2 trial, this research focuses on assessing the treatment's efficacy in an initial, smaller group of participants.

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 participate if you need other systemic cancer treatments or high doses of steroids.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that GB1211 is being tested with pembrolizumab to determine its safety for treating certain cancers. Pembrolizumab, already approved for other cancer types, has a well-documented safety profile. Most patients tolerate it well, though some may experience fatigue or a rash.

GB1211 is newer, so less information is available. However, studies are assessing its safety when combined with pembrolizumab. Since this trial is in phase 2, the treatment has already passed initial safety tests in earlier phases. This suggests the combination is likely safe, but researchers continue to monitor for any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of GB1211 and pembrolizumab for melanoma and head & neck cancer because it introduces a fresh approach to treatment. Unlike the standard immunotherapies, which mainly rely on pembrolizumab alone to block the PD-1 pathway and unleash the immune system against cancer cells, GB1211 targets galectin-3, a protein that can suppress immune responses and aid tumor growth. By combining GB1211 with pembrolizumab, the treatment aims to enhance the immune system's ability to fight cancer more effectively. This dual-action approach could potentially improve patient outcomes by overcoming resistance issues seen with current therapies.

What evidence suggests that this trial's treatments could be effective for melanoma and head & neck cancer?

In this trial, participants will receive either a combination of GB1211 with pembrolizumab or pembrolizumab alone. Research has shown that combining GB1211 with pembrolizumab may help treat advanced melanoma and head and neck cancer. Researchers are studying GB1211 for its potential to enhance the effects of pembrolizumab, a well-known cancer treatment. Early results suggest that GB1211 might improve the immune system's response to cancer cells. Pembrolizumab aids the immune system in fighting cancer by blocking a protein that weakens the immune response. Ongoing studies aim to determine if adding GB1211 can improve patient outcomes. ^{1 2 4 5 6}

Who Is on the Research Team?

Brendan D. Curti, MD

Principal Investigator

Providence Health & Services

Are You a Good Fit for This Trial?

Adults with advanced melanoma or head and neck squamous cell carcinoma that's unremovable or has spread, and who have not responded to certain chemotherapies. They must be in a condition where they can live for at least another 12 weeks, agree to prevent pregnancy, and haven't had specific treatments that would exclude them.

Inclusion Criteria

You are expected to live for more than 12 weeks.

I have melanoma that cannot be removed by surgery or has spread, confirmed by a biopsy.

I am not currently experiencing any bleeding.

Exclusion Criteria

You have an ongoing autoimmune disease, except for thyroiditis or vitiligo.

You are currently receiving other cancer treatments, including experimental ones.

I haven't had cancer treatment in the last 3 weeks or 5 half-lives before starting the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either GB1211 + pembrolizumab or pembrolizumab + placebo

63 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GB1211
• Pembrolizumab
• Placebo

Trial Overview The trial is testing the effectiveness of GB1211 combined with Pembrolizumab versus Pembrolizumab with a placebo in treating metastatic melanoma or head and neck cancer. The goal is to see which combination works better for these conditions.

How Is the Trial Designed?

Group I: GB1211 + Pembrolizumab Experimental Treatment 2 Interventions

GB1211 will be administered orally twice a day at 400mg in combination with standard pembrolizumab treatment.

Group II: Pembrolizumab Monotherapy Placebo Group 2 Interventions

Placebo will have the same appearance as GB1211 and administered orally twice a day in combination with standard pembrolizumab treatment.

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Providence Cancer Center

Collaborator

Trials

2

Recruited

100+

Providence Cancer Center, Earle A. Chiles Research Institute

Collaborator

Trials

21

Recruited

500+

Galecto Biotech AB

Industry Sponsor

Trials

9

Recruited

580+

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

A 69-year-old patient with relapsed squamous cell carcinoma showed significant improvement after 14 cycles of pembrolizumab, indicating its efficacy as a second-line treatment for metastatic head and neck cancer.

The patient developed severe immune-related adverse effects, specifically grade 4 mucositis and esophagitis, highlighting the importance of monitoring for such complications in patients receiving PD-1 inhibitors like pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. Acero Brand, FZ., Suter, N., Adam, JP., et al.[2019]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

In a phase III trial, pembrolizumab, a single-agent treatment, showed significant effectiveness in patients with head and neck tumors that had high PD-L1 expression, leading to deep and lasting responses.

This study highlights the potential of pembrolizumab as a first-line therapy for this specific group of cancer patients, suggesting a targeted approach based on PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

Citations

1. ir.galecto.com ir.galecto.com/news-releases/news-release-details/galecto-announces-first-patient-dosed-investigator-initiated

Galecto Announces First Patient Dosed in an Investigator ... The study aims to evaluate the safety and efficacy of GB1211 at a dose of 100mg twice daily in combination with pembrolizumab for the treatment of metastatic ...

2. clinconnect.io clinconnect.io/trials/NCT05913388

GB1211 and Pembrolizumab Versus ... - ClinConnect This clinical trial is studying the effectiveness of two treatments for patients with advanced skin cancer (metastatic melanoma) or certain types of throat ...

3. clinicaltrials.eu clinicaltrials.eu/inn/gb1211/

Gb1211 – Application in Therapy and Current Clinical ... A study investigating GB1211 in combination with pembrolizumab (a cancer immunotherapy drug) for treating metastatic melanoma and head and neck cancer.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/453595

GB1211 and Pembrolizumab Versus ... The purpose of this study is to determine the objective response of GB1211 and pembrolizumab versus pembrolizumab and placebo in patients ...

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/453595

GB1211 and Pembrolizumab Versus ... - Carebox Connect The purpose of this study is to determine the objective response of GB1211 and pembrolizumab versus pembrolizumab and placebo in patients with advance ...

6. careacross.com careacross.com/clinical-trials/trial/NCT05913388

GB1211 and Pembrolizumab Versus ... Summary: The purpose of this study is to determine the objective response of GB1211 and pembrolizumab versus pembrolizumab and placebo in patients with advance ...