BAT6021 in advanced solid tumours: a Phase 1 anti-TIGIT programme closed on the class's Phase 3 data

What was tried

Bio-Thera Solutions ran NCT05073484, a Phase 1, multi-center, open-label study of BAT6021 given alone or in combination with BAT1308 in patients with advanced solid tumors. BAT6021 is a recombinant humanized anti-TIGIT antibody and BAT1308 a recombinant humanized anti-PD-1 antibody. The design was non-randomized and sequential with no masking. Monotherapy escalation ran through 10, 30, 100, 300, 600 and 900 mg, and combination cohorts paired 100, 300 or 600 mg of BAT6021 with 300 mg of BAT1308.

The primary outcome measures were dose-limiting toxicity over a minimum of 21 days after first dose and serious adverse events. Secondary measures covered pharmacokinetics (Cmax) and immunogenicity. Eligibility required adults with confirmed advanced or metastatic solid tumors refractory to standard therapy, ECOG status 0 or 1, and measurable disease by RECIST v1.1.

Actual enrollment was 13 patients across three listed locations. The study started on 29 October 2021 and recorded actual primary completion and completion on 30 March 2023. The record was updated to terminated on 15 October 2026, roughly 43 months later. No results have been posted. The whyStopped field is unusually candid: "Based on the disclosed global research data on the same target drugs, the company has carefully considered and decided to terminate the project to optimize the existing research pipeline."

The biological hypothesis

TIGIT is an inhibitory receptor on T cells and NK cells that binds CD155 (PVR) and CD112 (nectin-2), competing with the activating receptor CD226. Blocking TIGIT was expected to release that brake and, in antibodies with active Fc, to deplete TIGIT-high regulatory T cells through antibody-dependent cellular cytotoxicity. Bio-Thera designed BAT6021 for that second mechanism, describing it at first dosing in January 2022 as "a monoclonal antibody with enhanced ADCC targeting TIGIT."

The evidence base was clinical and literature-derived rather than genetic. Open Targets scores the TIGIT to cancer association at 0.3076, from a literature score of 0.8671 and a clinical score of 0.4627, with no genetic association score returned and no safety liabilities recorded. Open Targets lists seven TIGIT drug programmes, four at Phase 3 (ociperlimab, tiragolumab, domvanalimab, vibostolimab) and three that did not advance past Phase 2 (etigilimab, ASP-8374, IBI-939). The class rested on one positive randomized signal, the CITYSCAPE Phase 2 study, which reported an objective response rate of 37% versus 21% with atezolizumab alone in the PD-L1-high population and 31.3% versus 16.2% overall.

What actually happened

The trial finished dosing in March 2023 without a posted result. What killed the programme happened elsewhere, in other companies' Phase 3 readouts.

Roche's SKYSCRAPER-01 and SKYSCRAPER-02 failed to improve survival outcomes. BeOne Medicines discontinued ociperlimab after AdvanTIG-302 read out negative. Merck's KeyVibe-003 and KeyVibe-007 met predetermined futility criteria for overall survival in 2025 and vibostolimab was discontinued. In December 2025 Arcus and Gilead stopped the Phase 3 STAR-221 study of domvanalimab after an independent data monitoring committee found the combination did not improve overall survival, and the midstage Edge-Gastric study was stopped alongside it. Bio-Thera's termination notice, posted in October 2026, points at precisely this body of disclosed data.

Claidex already held four TIGIT post-mortems: ociperlimab in first-line PD-L1-high non-small cell lung cancer, tiragolumab in adjuvant non-small cell lung cancer, and the vibostolimab coformulation in BCG-unresponsive bladder cancer and in adjuvant melanoma. Two were efficacy failures, one a safety signal, one a strategic reprioritisation. BAT6021 makes five.

Failure mechanism, best guess

The archetype is strategic reprioritisation, and it is the correct label. This trial did not fail. It was closed because the hypothesis it tested had been falsified at Phase 3 scale by better-powered studies against the same target.

The underlying class failure has at least three candidate mechanisms, none settled. The first is Fc design. Preclinical work suggests anti-TIGIT activity depends on Fc effector function, and a recent review notes that an Fc-deficient variant lost efficacy in a mouse model while ociperlimab's Fc function was described as critical. Most discarded clinical candidates were Fc-enabled, the design BAT6021 used. The second is CD226 co-dependency. Releasing the TIGIT brake only helps if the activating receptor it competes with is still present, and CD226 is downregulated on exhausted tumour-infiltrating lymphocytes. The third is ligand redundancy. CD155 and CD112 are also read by CD96 and PVRIG, so blocking one receptor leaves the axis partly intact.

Biomarker selection compounded all three. The same review tested the baseline TIGIT to CD226 ratio against response and found no association in GSE91061 (n = 49, p = 0.149) or IMvigor210 (n = 298, p = 0.624), and none with overall survival in IMvigor210 (log-rank p = 1.0). The authors frame these as hypothesis-generating because they were not corrected for multiple comparisons. The class advanced to Phase 3 without a patient-selection marker that works.

How to prevent this next time

No endpoint data were posted for this trial, and 13 patients in an open-label dose escalation would not support an efficacy inference in any case. The levers below are qualitative.

Base-rate adjustment is the dominant one. A Phase 1 anti-TIGIT antibody starting in late 2021 entered a field whose clinical case rested on a single Phase 2 response-rate comparison in one tumour type. The prior on a second-wave, mechanistically undifferentiated entrant was low from the start, and it should have been written down before the first patient was dosed.

Mechanistic differentiation is the second lever. BAT6021 shared its Fc-enabled design with candidates already in Phase 3. A programme entering a crowded class four years behind the leaders needs a stated reason it would succeed where they might not, whether Fc silencing, bispecific format or a defined patient-selection marker.

Biomarker enrichment is the third. No anti-TIGIT programme carried a validated predictive marker into late development, and the one Phase 3 reported to show gains in both progression-free and overall survival, SKYSCRAPER-08 in oesophageal squamous cell carcinoma, suggests the biology may be real in selected contexts rather than absent.

The single highest leverage change would have been to tie the programme's continuation decision to a pre-registered external readout gate on the first Phase 3 in the class, instead of running a dose escalation to completion and then waiting three years to record the termination.

What this means for similar programs

The recomputed Mechanism Risk Score for TIGIT is 80 of 100, in the red band. Phase burden contributes 25.7 of 30, archetype severity 19.9 of 25, recency 12.0 of 15, genetic deficit 10.4 of 15 and saturation 12.0 of 15 across 8 distinct programmes. Five documented terminations against one target in five months is the clearest saturation signal in the Claidex graph.

Two structural lessons carry past TIGIT. A target validated by a single Phase 2 response-rate comparison is not validated. And a registry record that sits unchanged for three years after dosing stops is not a reliable picture of what a company is developing.

Open questions

What safety, pharmacokinetic and immunogenicity data did the 13 dosed patients generate, and will any of it be released? How was BAT6021 Fc-engineered, and how did its ADCC potency compare with tiragolumab and ociperlimab? Does the Fc-silent subclass, including domvanalimab and the bispecific rilvegostomig, behave differently enough to separate the Fc hypothesis from a flat negative on the axis?

Sources

1. • ClinicalTrials.gov, NCT05073484, BAT6021 and BAT1308 in advanced solid tumor: https://clinicaltrials.gov/study/NCT05073484 - Open Targets Platform, TIGIT (ENSG00000181847) and cancer (MONDO_0004992), accessed 22 October 2026: https://platform.opentargets.org/target/ENSG00000181847 - Bio-Thera Solutions, first patient dosed in Australia for BAT6021, an ADCC-enhanced monoclonal antibody targeting TIGIT, 24 January 2022: https://www.businesswire.com/news/home/20220124005351/en/ - Smail SW, et al. The Right Key, the Wrong Lock: TIGIT Checkpoint Blockade and the Road to Precision Immunotherapy. Pharmaceutics, 2026. https://- Sundstrom P, et al. Anti-TIGIT therapies: a review of preclinical and clinical efficacy and mechanisms. Cancer Immunol Immunother, 2025. https://- Cai L, et al. Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy. J Hematol Oncol, 2023. https://- Chu X, et al. Co-inhibition of TIGIT and PD-1/PD-L1 in cancer immunotherapy: mechanisms and clinical trials. Mol Cancer, 2023. https://- Brazel D, et al. Tiragolumab (anti-TIGIT) in SCLC: Skyscraper-02, a towering inferno. Lung Cancer (Auckl), 2023. https://- Xu J, et al. Atezolizumab with or without tiragolumab in unresectable oesophageal squamous-cell carcinoma. Ann Oncol, 2026. https://- Fierce Biotech, Arcus discontinues Gilead-partnered TIGIT trials due to futility, 12 December 2025: https://www.fiercebiotech.com/biotech/arcus-halts-gilead-partnered-tigit-trials-biotech-reworks-rd-focus - The solid tumor microenvironment changes the hierarchy of CD155 and CD112 receptors, shaping checkpoint biology. bioRxiv, 2 August 2026. https://- TIGIT-NECTIN2/3 signaling preserves ignorant CD8+ T cells for favorable immune checkpoint outcomes. bioRxiv, 8 May 2026. https://- Claidex claim graph, TIGIT post-mortems: /claim/ociperlimab-tigit-advantig-302-nsclc-class-failure, /claim/tiragolumab-tigit-adjuvant-nsclc-phase3-class-efficacy-failure, /claim/vibostolimab-favezelimab-tigit-bcg-unresponsive-nmibc-keynote-057-phase2-strategic-termination, /claim/vibostolimab-pembrolizumab-tigit-adjuvant-melanoma-keyvibe-010-phase3-safety-termination - openFDA drug event endpoint, queried for BAT6021 on 22 October 2026, no matching records: https://api.fda.gov/drug/event.json.