SHY Therapeutics starts Phase 1 dose-finding trial of proteasome inhibitor SHY-ONC6
The 30-patient study will test dose-limiting toxicity and a recommended Phase 2 dose in a tumor field where proteasome inhibition has run mostly in blood cancers.
Executive Summary
- SHY Therapeutics opened enrollment in a Phase 1 trial testing its proteasome inhibitor in patients with advanced tumors who have exhausted standard therapies.
- Proteasome inhibition is an established approach in blood cancers, but it has rarely been tested as a targeted mechanism against tumors outside that setting, making this trial a test of whether that biology extends beyond its established use.
- The study is designed to find a tolerable dose and recommended Phase 2 dose before it can generate any signal on tumor response, so the near-term reading is on safety, not efficacy.
- No other industry-sponsored Phase 1 trial currently pairs a proteasome-inhibitor mechanism with a tumor population outside blood cancers, positioning this study as an early, largely unaccompanied test of that combination.
The trial
The study, registered as NCT07705334 and also known as Luca-1, opened for recruitment on June 29, 2026, and is targeting 30 patients across sites in the United States. Eligible patients have tumors including triple-negative and HR-positive breast cancer, colon cancer, gastric cancer, hepatocellular carcinoma, non-small cell lung cancer, mesothelioma, pancreatic cancer, castration-resistant prostate cancer, and soft-tissue sarcoma that has progressed on or is intolerant of standard therapies. The trial is not registrational, and its primary completion date is set for May 15, 2027. NCT07705334A Study of SHY-ONC6, a Novel Proteasome Inhibitor, in Adults With Advanced or Metastatic Solid TumorsNCT07705334
What it will test
The trial's primary measures are the incidence of dose-limiting toxicities, adverse events, and serious adverse events during the first 21-day cycle, the maximum tolerated dose determined through a Bayesian dose-escalation design targeting a 30% dose-limiting toxicity rate, and a recommended Phase 2 dose. Secondary measures include objective response rate, duration of response, and progression-free survival by RECIST v1.1, along with standard pharmacokinetic parameters. Because the design is a dose-finding study, the near-term information value sits in tolerability and dosing, with any anti-tumor activity signal following only after a dose is selected. NCT07705334A Study of SHY-ONC6, a Novel Proteasome Inhibitor, in Adults With Advanced or Metastatic Solid TumorsNCT07705334
The mechanism's track record
Proteasome inhibitors including bortezomib, carfilzomib, and ixazomib have an established history in multiple myeloma, where several have reached Phase 3 and approval. In tumors, the mechanism has been tested only sparingly: prior Phase 1 studies of oprozomib (Amgen) and marizomib (Celgene) tested proteasome inhibition in -tumor populations, and Chia Tai Tianqing Pharmaceutical Group's TQB3602 is currently in Phase 1 testing for advanced malignant tumors. Industry field activity around the proteasome target has declined overall, with 106 recent trials against 11,130 older ones tracked in the broader dataset.
Competitive position
Among industry trials combining a proteasome-inhibitor mechanism with a tumor indication, SHY-ONC6's trial is the only one currently active at Phase 1. The closest direct comparators, TQB3602, oprozomib, and marizomib, share the same target and modality but were tested in earlier eras and different specific tumor populations. Given how little the mechanism has been tried against tumors of this kind, a tolerable dose paired with any objective response by RECIST v1.1 would be the result that establishes whether proteasome inhibition has a place in this setting beyond its established use in blood cancers.
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