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 oncology. It has high affinity for human galectin‑3 (Kd ≈ 25 nM) and was selected following a medicinal chemistry program optimizing potency, selectivity, and oral bioavailability. A first‑in‑human study in healthy participants characterized pharmacokinetics and tolerability, and early patient studies have explored biomarker changes in decompensated cirrhosis and combination therapy with atezolizumab in first‑line NSCLC. (pmc.ncbi.nlm.nih.gov)
Notes: As of the most recent public reports, human data include one completed Phase 1 in healthy volunteers, an exploratory Phase 1b/2a biomarker study in decompensated cirrhosis, and early, small open‑label dose‑finding data in NSCLC; no definitive, controlled efficacy results in patients have been published. (pmc.ncbi.nlm.nih.gov, ir.galecto.com, oncologypro.esmo.org)
Last updated: Sep 2025
Goal: Evaluate whether adding the oral galectin‑3 inhibitor GB1211 to pembrolizumab improves objective response compared with pembrolizumab plus placebo in metastatic melanoma or recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
Patients: Adults (≥18 years) with unresectable or metastatic melanoma (including mucosal or unknown primary) or HNSCC with progression during or after platinum-based chemotherapy. Prior anti‑PD‑1/PD‑L1 is allowed if ≥6 months since last dose with documented progression; treatment‑naïve melanoma allowed. ECOG 0–2, anticipated survival >12 weeks, no active autoimmune disease (except thyroiditis or vitiligo), no untreated brain metastases, no recent systemic therapy, adequate hematologic and hepatic function, and no active infections (HIV, HBV, HCV excluded).
Design: Randomized, double-blind, placebo-controlled Phase II, stratified by diagnosis (melanoma vs OHN/HNSCC) and number of prior systemic therapies. Allocation 1:1 to experimental combination vs control. Planned enrollment 92.
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, orally bioavailable small‑molecule inhibitor of galectin‑3, a lectin implicated in immune suppression, tumor progression, and resistance to checkpoint blockade. Preclinical data show reversal of galectin‑3–mediated inhibition of PD‑1/PD‑L1 interactions and antitumor activity. Early human experience includes favorable tolerability in healthy volunteers and exploratory oncology combinations suggesting activity at 100 mg BID; definitive controlled efficacy data in cancer are not yet established.
Outcomes: Primary: Overall response rate by imaging from randomization until first documented progression (up to 63 weeks). Secondary: paired tumor galectin‑3 expression changes (screening and Day 68); longitudinal characterization of myeloid-derived suppressor cells as a predictive biomarker (to Day 85); frequency of immune‑mediated adverse events (through week 63); immunologic activity including CD4+ memory phenotype, CD8+ effector phenotype, and tumor‑specific T cells (around Day 85).
Burden on patient: Moderate. Beyond standard pembrolizumab visits and imaging, the study includes twice-daily oral dosing and placebo/GB1211 adherence, paired tumor biopsies (screening and Day 68) and serial immune monitoring blood draws through approximately 12 weeks and up to week 63 for safety assessments. The paired biopsies and intensified immunophenotyping increase procedural and visit burden compared with pembrolizumab alone, but there are no intensive pharmacokinetic schedules reported and imaging frequency appears similar to standard of care.
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