Roche Terminates Phase II/III SKYSCRAPER-06 Trial of Tiragolumab in First-Line Non-Squamous NSCLC Following Failure to Meet PFS and OS Endpoints

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It is particularly memorable that in August 2023, Roche announced the results of the second interim analysis of the Phase 3 clinical trial Skyscraper 01 study.

Although the OS data was not yet mature at the time, the mOS data for the combination of TIGIT and PD-L1 was significantly better than the data for PD-L1 monotherapy (22.9 months vs 16.7 months).

On the same day, the stock prices of TIGIT track pharmaceutical companies were almost all in the red. Arcus rose by 22.43%, iTeos by 14.89%, and Compugen by 19.61%.

Roche (Genentech) is the discoverer and leading pioneer in the research and development of the TIGIT target.In 2021, Roche focused on TIGIT monoclonal antibodytiragolumabConducted more than 10 Phase II/III clinical trials.

It can be said that,RocheEvery move of TIGIT tugs at the nerves of everyone in this field.

Recently, Roche's TIGIT has delivered more bad news……

On July 4, 2024, Roche announced that its Phase II/III KYSCRAPER-06 study did not meetPrimary EndpointPFS、OS。

Figure 1: Roche Press Release (Source: businesswire)

A total of542 previously untreated patients with advanced non-squamous NSCLC,EvaluationTIGIT Monoclonal AntibodyTiragolumab + PD-L1 (Tecentriq) + Chemotherapy vs PD-1 (K drug) + Chemotherapy: Safety and Efficacy.

ResearchThe results showed that the hazard ratio (HR) for one of the primary endpoints, PFS, was 1.27 (95% CI: 1.02, 1.57), and the HR for overall survival (OS) was 1.33 (95% CI: 1.02, 1.73); the data remain immature.

In the intent-to-treat population, the efficacy of the TIGIT combination group was lower than that of the control group (K drug) in terms of PFS and OS, with consistent overall safety.

Given that the HR value has significantly exceeded 1, and the lower limit of the 95% confidence interval has also surpassed 1, Roche decided to terminate this study ahead of schedule.

And before this, Gilead, BMS,Merck & Co.has also made a similar decisionDefinition.

GileadCancelled its anti-TIGIT antibody (domvanalimab）+ PD-1（ zimberelimab）The Phase III ARC-10 Study of K Drug in First-Line Advanced NSCLC Treatment.

WillThe focus of research and development has shifted to the efficacy of domvanalimab + zimberelimab + chemotherapy versus Keytruda + chemotherapy in first-line treatment for all NSCLC patients, regardless of PD-L1 expression levels.

As for BMS, it also terminated its own TIGIT monoclonal antibody.BMS-986207The research shifted to the development of the TIGIT/CD96 bispecific antibody BMS-986442 (AGEN1777).

Finally, there is Merck, in May this year,Announcement of the Termination of Ongoing MK-7684A (K Drug +TIGIT AntibodyVibostolimab vs K Drug MonotherapyPhase III KeyVibe-010 Study in Adjuvant Treatment of High-Risk Stage IIB-IV Melanoma Patients After Surgical Resection.

The attitude of MNCs makesThe future development prospects of TIGIT have become unclear.

Including this timeNegative Results of KYSCRAPER-06 Study,RocheTIGIT has suffered three defeats in the lung cancer field.

As early as 2022, Roche had two setbacks. One was "tiragolumab+Tecentriq + Chemotherapy”First-line treatment for extensive-stage SCLC Phase III - SKYSCRAPER-02, did not meet PFS endpoint.

Another time was,Skyscraper—01 Study's First Interim Analysis Also Fails to Reach PFS Endpoint.

The controversy surrounding the TIGIT target has never stopped.

Unlike PD-1 antibody monotherapy, which can achieve clinical benefits on its own, previous studies suggest that TIGIT itself lacks standalone druggability and needs to be combined with PD-1/PD-L1 monoclonal antibodies.

NamelyTIGIT monoclonal antibody, when used in combination with PD-1 monoclonal antibody and PD-L1 monoclonal antibody, can enhance the effects of the latter.

Since the first PD-1 monoclonal antibody was approved by the FDA in 2014, immune checkpoint inhibitors represented by PD-1/PD-L1 have embarked on a new journey in anti-tumor treatment.

Today, PD-1/PD-L1 has becomePaved the waySuch a large market, once there isTIGIT's Initial Public Offering, that isA super blockbuster worth tens of billions of dollarsBomb.

Roche is willing to take a chance, and so is GSK.

June 24, 2024GSKA Phase III Clinical Trial of PD-1 Antibody Dostarlimab + TIGIT Antibody Belrestotug in First-Line Treatment of NSCLC Patients with High PD-L1 Expression Registered on Clinicaltrials.gov.

GSK has becomeFollowing Roche, BeiGene, Merck, and Gilead, anotherPD-1+TIGIT Pushed toPlayers in Phase III clinical trials.

In addition, except forTIGIT monoclonal antibody,TIGITBispecific AntibodyThere is no doubt that it can also become a breakthrough in the future. In China alone, several pharmaceutical companies such as Innovent, Hengrui, Henlius, and Promab have laid out their plans, and all have entered the clinical stage.

Cover image source: pixabay

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