Anti-TIGIT Plus Immunotherapy ‘Promising’ in NSCLC, Esophageal Cancer

Derick Alison
Derick Alison
7 Min Read

Combination treatment with an investigational anti-TIGIT drug plus a PD-L1 inhibitor was well tolerated and demonstrated promising activity in patients with metastatic non-small cell lung cancer (NSCLC) and esophageal cancer who had no prior exposure to immunotherapy, a phase I trial found.

In the study’s metastatic NSCLC cohort, which selected for PD-L1 expression, six of 13 patients (46%) responded to anti-TIGIT tiragolumab plus atezolizumab (Tecentriq), reported Byoung Chul Cho, MD, PhD, of Yonsei University College of Medicine in Seoul, South Korea, and colleagues.

And five of 18 patients (28%) with metastatic esophageal cancer responded to the combination; this group was not selected for PD-L1 expression.

Median durations of response in the two cohorts reached 24.2 months (95% CI 9.7 to not reached [NR]) and 15.2 months (95% CI 7.0 to NR), respectively. There were no dose-limiting toxicities, according to the results in JAMA Oncology.

The treatment strategy “may amplify the magnitude and quality of tumor-specific T-cell responses and provide meaningful antitumor activity,” the authors wrote. “These findings support the continued investigation of dual TIGIT/programmed death ligand 1 inhibition in patients with advanced solid tumors.”

While characterizing these results as “encouraging” in an accompanying editorial, Aung Naing, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues said “interpretative caution applied to phase I trials is paramount, as they cannot conclusively affirm intervention efficacy — a notion further underscored by some phase III trials … failing to meet primary endpoints.”

For example, the SKYSCRAPER-02 trial showed no survival improvement with the addition of tiragolumab to atezolizumab plus chemotherapy for patients with untreated extensive-stage small cell lung cancer.

Last month, developer Roche “inadvertently” released results from an interim overall survival (OS) analysis of the phase III SKYSCRAPER-01 trial investigating tiragolumab and atezolizumab versus atezolizumab alone as first-line treatment for PD-L1-high NSCLC. Those OS results, while not mature at the time of the analysis, showed a numerical advantage in favor of the tiragolumab arm (median 22.9 vs 16.7 months, respectively; HR 0.81, 95% CI 0.63-1.03), according the press release.

“Anti-TIGIT therapy stands at a crossroads of promise and complexity,” wrote Naing and colleagues. “Early-phase trials, although enlightening, are provisional in nature. A synergistic approach encompassing baseline immune characterization, sequential therapy, and comprehensive [tumor microenvironment] analysis holds the potential to advance therapeutic paradigms.”

In addition to the SKYSCRAPER-01, tiragolumab in combination with atezolizumab is being further investigated in the phase II CITYSCAPE study in advanced PD-L1-positive NSCLC, and in the phase III SKYSCRAPER-07 and SKYSCRAPER-08 trials in metastatic esophageal cancer.

The current study was a multicenter (13 sites in Australia, Canada, France, Korea, Spain, and the U.S.), open-label, dose-escalation and dose-expansion phase Ia/Ib nonrandomized controlled trial involving patients with advanced solid tumors for whom standard treatment did not exist or was ineffective. Starting in 2016, patients received tiragolumab intravenously every 3 weeks in phase Ia (n=24) and the combination of the two drugs every 3 weeks in phase Ib (n=49). Beyond NSCLC and esophageal cancer, other tumor types in the trial included colorectal breast, head and neck, and ovarian cancers.

Among the phase Ia and Ib dose-escalation cohorts, the median age was 60 and 54 years, respectively, more than half of the patients were female (58% and 51%), and more than a third had received four or more prior cancer therapies.

Cho and colleagues reported that while there were no objective responses in phase Ia, four patients did experience prolonged stable disease with tumor shrinkage. There was evidence of antitumor activity in three of these patients (6%) in phase Ib.

Combining responders plus patients with stable disease in the NSCLC and esophageal cancer cohorts yielded disease control rates of 77% and 50%, respectively.

No maximum-tolerated dose for tiragolumab was identified, and the recommended phase II dosage is 600 mg given once every 3 weeks.

The most frequent treatment-related adverse events (AEs) were fatigue (21%) in phase Ia and pruritus (10%) in phase Ib, with the majority of AEs being low-grade. Immune-mediated AEs occurred in 17% of patients during phase Ia and 59% during Ib, and were mostly low-grade.

The authors observed a similar safety profile with tiragolumab alone and in combination with atezolizumab. The most common immune-mediated AE was rash (54% of patients with NSCLC and 38% with esophageal cancer). The majority of treatment-related AEs were low-grade. There were no grade 5 AEs or immune-mediated AEs related to tiragolumab and/or atezolizumab.

Study limitations included the small sample size for each tumor type, the poor prognosis of the study population, and that many patients had received prior immunotherapy.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

This study was sponsored by F. Hoffmann-La Roche.

Cho, co-authors, and editorialists reported multiple relationships with industry, including with the study funder.

Primary Source

JAMA Oncology

Source Reference: Kim TW, et al “Anti-TIGIT antibody tiragolumab alone or with atezolizumab in patients with advanced solid tumors: A phase 1a/1b nonrandomized controlled trial” JAMA Oncol 2023; DOI: 10.1001/jamaoncol.2023.3867.

Secondary Source

JAMA Oncology

Source Reference: Hajjar J, et al “Unlocking the potential of anti-TIGIT therapy — between promise and challenges” JAMA Oncol 2023; DOI:10.1001/jamaoncol.2023.3835.

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