Sponsor: Providence Health & Services (other)
Phase: 2
Start date: Feb. 29, 2024
Planned enrollment: 92
GB1211 (selvigaltin) is an oral, small‑molecule inhibitor of galectin‑3 being developed for fibrotic liver disease and as a combination partner with immune checkpoint inhibitors in oncology. Early human studies have established acceptable safety and predictable pharmacokinetics; exploratory oncology and liver-disease signals have been reported in conference presentations and company updates. (pubmed.ncbi.nlm.nih.gov)
Program update: As of late 2023, the sponsor indicated it would not initiate the randomized Part B and would redirect resources, while continuing to support an investigator‑initiated phase 2 study of GB1211 plus pembrolizumab in melanoma/HNSCC. (galecto.gcs-web.com)
Decompensated liver cirrhosis (GULLIVER‑2, NCT05009680):
Notes: Peer‑reviewed efficacy publications in patient populations have not yet been identified as of October 7, 2025; reported anti‑tumor responses and liver biomarker improvements derive from conference abstracts and sponsor communications and require confirmation in larger, controlled studies. (oncologypro.esmo.org)
Last updated: Oct 2025
Goal: Evaluate whether adding the oral galectin‑3 inhibitor GB1211 to pembrolizumab improves objective response compared with pembrolizumab plus placebo in advanced metastatic melanoma and recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
Patients: Adults (≥18) with unresectable or metastatic melanoma (including mucosal or unknown primary) or HNSCC with progression during/after platinum chemotherapy. Prior anti‑PD‑1/PD‑L1 allowed if last dose ≥6 months and radiographic progression documented; treatment‑naïve melanoma permitted. ECOG 0–2, life expectancy >12 weeks, no active autoimmune disease (exceptions: thyroiditis, vitiligo), no untreated brain metastases, no recent systemic anticancer therapy, and adequate hematologic and organ function. Key exclusions include prior galectin antagonist, active infection, Child‑Pugh C hepatic impairment, need for supraphysiologic steroids, and unresolved immune‑mediated toxicities.
Design: Randomized, double‑blind, placebo‑controlled, phase II study with stratification by diagnosis (melanoma vs oral/head and neck cancer) and number of prior systemic therapies. Allocation is 1:1 to experimental combination or control. Planned follow‑up for efficacy and safety through approximately 63 weeks.
Treatments: Experimental arm: GB1211 400 mg orally twice daily plus standard pembrolizumab. Control arm: matching oral placebo twice daily plus standard pembrolizumab. GB1211 (selvigaltin) is a selective small‑molecule inhibitor of galectin‑3, a lectin implicated in tumor immune evasion, fibrosis, and modulation of checkpoint efficacy. Preclinical data show reversal of galectin‑3–mediated interference with PD‑1/PD‑L1 interactions and antitumor immune enhancement. Early clinical experience has demonstrated acceptable tolerability in healthy volunteers and preliminary safety and activity signals in small oncology cohorts when combined with checkpoint blockade; definitive efficacy in controlled oncology studies has not yet been established. Pembrolizumab is a standard anti‑PD‑1 antibody used across melanoma and HNSCC.
Outcomes: Primary: Overall response rate by imaging from randomization to first documented progression, assessed up to 63 weeks. Secondary: Changes in tumor galectin‑3 expression in paired biopsies (screening and day 68); characterization of myeloid‑derived suppressor cells over time as a predictive biomarker; frequency of immune‑mediated adverse events; immunologic activity measures including CD4+ memory phenotype T cells, CD8+ effector phenotype T cells, and tumor‑specific T cells at protocol‑specified time points (notably day 85).
Burden on patient: Moderate. In addition to standard pembrolizumab visits and imaging, patients will take a twice‑daily oral study drug or placebo and undergo paired tumor biopsies, which adds procedural risk and visits. The immunologic biomarker program entails extra blood collections at specified time points to assess T‑cell phenotypes and MDSCs, increasing visit duration and needle sticks. Imaging and safety assessments are similar to standard of care for checkpoint therapy, and no intensive pharmacokinetic sampling is described. Travel and time commitments are greater around biopsy and biomarker time points (e.g., screening, day 68, day 85), but overall visit frequency is consistent with typical phase II immunotherapy trials.
Last updated: Oct 2025
Inclusion Criteria:
* Patients with unresectable or metastatic melanoma including unknown primary or mucosal melanomas. Histological confirmation of melanoma will be required by previous biopsy or cytology. Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression during or after platinum-containing chemotherapy are eligible. PD-L1 testing is not needed for OHN cancers.
* Patients who have received anti-PD1 or anti-PD-L1 in the past are eligible if it has been at least 6 months since the last anti-PD-1 or PD-L1 dose, they meet all other eligibility criteria and progression of malignancy has been documented on imaging. Progression for this patient subset is defined as the appearance of one or more new metastatic sites, or a 5% or greater increase in the sum of diameter of target lesions or an unequivocal increase in non-target site. Treatment naïve melanoma patients are eligible.
* Patients must be ≥ 18 years of age.
* ECOG performance status of 0-2.
* Women of childbearing potential must have a serum or urine pregnancy test performed within 72 hours prior to the start of protocol treatment. The results of this test must be negative in order for the patient to be eligible. In addition, women of childbearing potential as well as male patients must agree to take appropriate precautions to avoid pregnancy.
* No active bleeding.
* Anticipated lifespan greater than 12 weeks.
* Patients must sign a study-specific consent document.
Exclusion Criteria:
* Patients who have previously received a galectin antagonist.
* Patients with active autoimmune disease except for autoimmune thyroiditis or vitiligo.
* Patients with history of autoimmune colitis.
* Patients with untreated brain metastases. Patients with treated brain metastases who demonstrate control of brain metastases with follow-up imaging 4 or more weeks after initial therapy are eligible.
* Patients requiring other systemic oncologic therapy, including experimental therapies.
* Patients who have received anti-cancer treatment within 3 weeks or 5 half-lives before first study drug dose.
* Patients with Child-Pugh C hepatic impairment.
* Patients with active infection requiring antibiotics.
* Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.
* Need for steroids at greater than physiologic replacement doses. Inhaled corticosteroids are acceptable.
* Laboratory exclusions (to be performed within 28 days of enrollment):
* WBC \< 3.0 x 109/L
* Hgb \< 9.0 g/dL
* AST or ALT \> 1.5 times ULN
* Total bilirubin \> 1.9 g/dL, unless due to Gilbert's Syndrome. If Gilbert's Syndrome is present by clinical history, then direct bilirubin must by \< 3.0 g/dl.
* Active or known history of HIV
* Active or known history of Hepatitis B
* Active or known history of Hepatitis C
* Platelet counts \< 100 x 10E9 / L (100,000/ μL) without transfusion
* INR \> 1.5x ULN
* Inability to give informed consent and comply with the protocol. Patients must be judged able to understand fully the investigational nature of the study and the risks associated with the therapy.
* Any medical condition that in the opinion of the Principal Investigator would compromise the safety or conduct of the study procedures.
* Unresolved immune-mediated pneumonitis, diarrhea, elevation of hepatocellular enzymes or other toxicities requiring greater than physiological replacement doses of steroids.
Portland, Oregon, 97213, United States
[email protected] / 503-215-2691
Status: Recruiting