tiragolumab (RG6058)

P2, N=42, Recruiting, Georgetown University | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

P1/2, N=110, Completed, Hoffmann-La Roche | Recruiting --> Completed | N=336 --> 110 | Trial completion date: Jul 2025 --> Mar 2024 | Trial primary completion date: Jan 2025 --> Sep 2023

The addition of tiragolumab, an anti-TIGIT inhibitor, to chemotherapy plus atezolizumab demonstrated promising early results for lung cancer. Unfortunately, the phase 3 study SKYSCRAPER-02 did not confirm the anticipated benefit of tiragolumab combination in recalcitrant small-cell lung cancer,1 reiterating the need for a more accurate population selection in clinical trials.

P2, N=40, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting

P2, N=80, Active, not recruiting, SCRI Development Innovations, LLC | Trial completion date: Feb 2024 --> Jul 2024 | Trial primary completion date: Feb 2024 --> Jul 2024

P2, N=60, Not yet recruiting, The Netherlands Cancer Institute

P2, N=40, Not yet recruiting, Hoffmann-La Roche

P2, N=52, Not yet recruiting, National Cancer Institute (NCI)

P1/2, N=90, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | Trial completion date: Aug 2027 --> Aug 2024 | Trial primary completion date: Nov 2026 --> Aug 2024

P2, N=29, Terminated, Hoffmann-La Roche | Active, not recruiting --> Terminated; Sponsor's decision to terminate the study after Stage 1; will not proceed with Stage 2.

TIGIT is mainly expressed on T cells and is an inhibitory checkpoint receptor that binds to its ligand PVR in the tumor microenvironment. In contrast, Tiragolumab does not show an acidic pH-dependent binding enhancement. Our results provide valuable information that could help to improve the efficacy of therapeutic antibodies for cancer treatment.

P2, N=252, Completed, Genentech, Inc. | Active, not recruiting --> Completed

SKYSCRAPER-04 (NCT04300647) explored the clinical activity of Tiragolumab (T, anti-TIGIT) plus atezolizumab (A, anti-PD-L1) dual blockade (T+A) in patients (pts) with PD-L1+ cervical cancer. This exploratory analysis suggests that increased tumor immunity and mutation burden (TMB and PIK3CA-mut) correlates with improved ICB clinical outcomes. No biomarkers were clearly associated with tiragolumab outcome. These results are hypothesis generating and should be confirmed in an independent dataset.

P1, N=422, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2026 --> Apr 2026

P2; Not yet recruiting --> Recruiting

P1/2, N=8, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | N=118 --> 8 | Trial completion date: Dec 2023 --> Jul 2023 | Trial primary completion date: Dec 2023 --> Jul 2023

P2, N=58, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Feb 2024 --> Nov 2023

Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development.

P1/2, N=150, Recruiting, Hoffmann-La Roche | Trial completion date: Feb 2027 --> Sep 2028 | Trial primary completion date: May 2025 --> Sep 2025

P3, N=1150, Recruiting, Hoffmann-La Roche

P2; N=244 --> 7 | Trial completion date: Nov 2028 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Nov 2023; Sponsor made decision to terminate study.

P1/2, N=675, Recruiting, Hoffmann-La Roche | N=470 --> 675 | Trial completion date: Nov 2026 --> Sep 2027 | Trial primary completion date: Aug 2025 --> Jun 2026

Approximately, 30% of recurrent EC pts fall into this category. Pairing ICI with targeted therapies carries the potential to elicit prolonged anti-tumor effects. Atezolizumab (Atezo) is a humanized monoclonal PD-L1 inhibitor that has demonstrated monotherapy antitumor activity with an acceptable safety profile in relapsed recurrent EC...In cohort A, pts may be eligible for one of the following doublets: Atezo+ipatasertib (PIK3CA/PTEN/AKT1-altered cancers), Atezo+talazoparib (tumors with genomic loss of heterozygosity (LOH) ≥16%), Atezo+Trastuzumab emtansine (ERBB2/HER2 mutated and/or amplified tumors), and Atezo+Tiragolumab (MSI-H and/or TMB>10 mut/MB). The Atezo+bevacizumab (biomarker unmatched) arm is closed to enrollment...Pts will receive Atezo in addition to the targeted agent (at the study approved dosing schedule) until progression, unacceptable toxicity, pt or physician decision to withdraw from the study, death, or study termination. Pts in cohort B, will be eligible for inavolisib (PIK3CA/PTEN/AKT1-altered cancers) + letrozole. The primary endpoint for Cohort A is confirmed overall response rate (ORR) for each cohort, and for Cohort B is progression free survival at 6 months...As a platform study, additional arms may be added, as supported by evolving understanding of EC and molecular targets. EndoMAP is actively enrolling at 18 sites in the US with a target of 25 sites nationwide.

P1/2, N=32, Recruiting, National Taiwan University Hospital | Not yet recruiting --> Recruiting

Although two clinical studies on advanced lung cancer had positive results, the TIGIT-targeted antibody, tiragolumab, recently failed in two new trials. In this review, we highlight the current developments on TIGIT for cancer immunotherapy and discuss the characteristics and functions of TIGIT.

P2, N=96, Recruiting, Omico | Not yet recruiting --> Recruiting

P2, N=97, Recruiting, University Medical Center Groningen | Not yet recruiting --> Recruiting

Tiragolumab plus atezolizumab was well tolerated in Japanese patients with advanced/metastatic solid tumors, and no differences in tiragolumab PK characteristics were noted between Japanese patients enrolled in this study, and non-Japanese patients enrolled in a global phase III study. These results may support the inclusion of Japanese patients in ongoing global phase III clinical trials.

P1/2, N=40, Active, not recruiting, Hoffmann-La Roche | N=255 --> 40

"Haystack Oncology...has entered into a collaboration with Alliance Foundation Trials, LLC (AFT) for research use of Haystack Oncology's personalized MRD technology (Haystack MRD™) to analyze therapeutic response and provide molecular insights for AFT's interventional, randomized phase II clinical trial (AFT-57) in patients with unresectable stage III non-small cell lung cancer (NSCLC). The AFT-57 clinical study is supported by Genentech, a member of the Roche Group, and will explore the efficacy and safety of an anti-PD-L1 atezolizumab (Tecentriq^®) with or without tiragolumab (anti-TIGIT) in conjunction with chemoradiotherapy."

P2, N=178, Recruiting, Alliance Foundation Trials, LLC. | Not yet recruiting --> Recruiting

We summarize PK data from the phase 1a/1b GO30103 study of every 3 weeks (Q3W) sequential dosing of tiragolumab (2, 8, 30, 100, 400, 600, or 1200 mg) followed by atezolizumab (1200 mg), every 4 weeks (Q4W) sequential dosing (tiragolumab 840 mg followed by atezolizumab 1680 mg) and Q4W co-infusion (tiragolumab 840 mg plus atezolizumab 1680 mg). There were no meaningful differences in tiragolumab or atezolizumab exposure between the Q4W co-infusion and sequential dosing cohorts. ClinicalTrials.

P2; N=160; Not yet recruiting; Sponsor:Institut Curie

Eligible pts (confirmed LA or R/M ESCC; ECOG PS 0–1; no prior systemic tx) were randomized 1:1 to receive tira 600mg + atezo 1200mg + CT (paclitaxel 175mg/m2 + cisplatin 60–80mg/m2, local standard of care) or placebo + CT on Day 1 of each 21-day cycle (cycles 1–6); followed by tira + atezo or placebo maintenance until loss of clinical benefit/unacceptable toxicity. The study met both primary endpoints of IRF-assessed PFS and OS, demonstrating statistically significant and clinically meaningful improvements in PFS and OS for tira + atezo + CT over placebo + CT. Generally consistent benefit was observed across subgroups, including PD-L1 status. The safety profile was consistent with the known risks of the individual tx.

Eligible pts (locally advanced unresectable, or metastatic EC with no prior systemic treatment; ECOG PS 0–1) were randomized to receive: cisplatin 80mg/m2 + 5-FU 800mg/m2/24 hours on Days 1–5 of each cycle (CT); atezo 1200mg + cisplatin + 5-FU (atezo + CT); or tira 600mg + atezo + cisplatin + 5-FU (tira + atezo + CT) in 21-day cycles... Clinically meaningful improvements in INV-assessed ORR and PFS and a trend of improved OS were observed with tira + atezo + CT when compared with CT and atezo + CT. These results support the contribution of both tira and atezo in combination with CT. The safety profile was consistent with the known risks of the individual tx.

P2, N=15, Recruiting, National Cancer Institute (NCI) | Initiation date: Jan 2024 --> Sep 2023

P1, N=518, Active, not recruiting, Genentech, Inc. | Phase classification: P1a/1b --> P1

P1/2, N=340, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

Preliminary antitumor activity was demonstrated for the combination regimen in patients with cancer immunotherapy-naive metastatic NSCLC or EC. ClinicalTrials.gov Identifier: NCT02794571.

Ancillary analyses will be performed with peripheral and intratumoral immune biomarker assessments. This study is registered on ClinicalTrials.gov: NCT05259319, since February 28th, 2022.