American Association for Cancer Research Annual Meeting

American Association for Cancer Research Annual Meeting

April 15, 2018
2 min read

Taselisib monotherapy appears active in PIK3CA-mutated solid tumors

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Komal Jhaveri

CHICAGO — Taselisib demonstrated preliminary clinical activity and exhibited an acceptable safety profile as monotherapy for patients with PIK3CA-mutated locally advanced or metastatic solid tumors, according to results of a basket study presented at American Association for Cancer Research Annual Meeting.

“This study represents the largest basket study reported to date of PIK3CA-mutant tumors treated with a mutant-selective PI3K inhibitor,” Komal Jhaveri, MD, oncologist at Memorial Sloan Kettering Cancer Center, said during her presentation. “Signals of taselisib activity were observed in multiple tumor types, including confirmed responses in head and neck squamous cell carcinoma, cervical [cancer], endometrial [cancer] and other tumors.”

The PIK3CA gene — which encodes the alpha-isoform of the catalytic subunit of Class 1 PI3 kinases — often is mutated or amplified in solid tumors.

Taselisib (GDC0032/RG7604, Genentech/Roche) is an oral, selective inhibitor of Class 1 PI3K alpha, delta and gamma isoforms.

Results of prior preclinical and clinical studies suggested single-agent taselisib has activity in multiple PIK3CA-mutated tumor types, according to study background.

Jhaveri and colleagues conducted an open-label phase 1 study to assess taselisib for patients with PIK3CA-mutated tumors who did not respond to or progressed after at least one prior treatment. Enrolled patients were not candidates for other regimens known to offer clinical benefit.

The study included 11 subcohorts of patients with various solid tumor types, including endometrial cancer; bladder cancer; head and neck squamous cell carcinoma; cervical cancer; gastric/gastroesophageal junction cancer; small cell lung cancer; triple-negative breast cancer; colorectal cancer, excluding KRAS-mutated tumors; squamous tumors, excluding histologies included in other subcohorts; ovarian cancer; and those with PIK3CA-mutant tumors not otherwise specified, excluding colorectal, breast and non-small cell lung cancers.

Investigators centrally assessed archival or fresh tumor tissue for PIK3CA mutation amplification.

Patients received taselisib monotherapy dosed at 4 mg or 6 mg daily.

Tolerability and safety served as the primary endpoint. Secondary endpoints included antitumor activity as assessed by RECIST criteria.

Researchers had enrolled 146 patients at the time of data cutoff on May 1, 2017.

Investigators observed no new safety signals during the study, Jhaveri said.

Fifty-three patients (36.3%) experienced grade 3 or higher taselisib-related adverse events. Ninety-four patients (64.4%) experienced grade 1 or higher adverse events.

The most common adverse events included diarrhea (58.2%), nausea (39%), hyperglycemia (31.5%) and fatigue (30.8%).

Sixty-eight patients (46.6%) experienced serious adverse events. The most common taselisib-related serious adverse events included colitis (5.5%), diarrhea (4.1%) and hyperglycemia (3.4%).


Nine patients (6.2%) experienced grade 5 events. One patient (0.7%) died of septic shock determined to be related to taselisib.

Higher taselisib doses were associated with increased antitumor activity but decreased tolerability.

Adverse events led to dose reductions for 34 patients (23.3%), treatment interruption for 59 patients (40.4%) and study withdrawal for 14 patients (9.6%).

Researchers reported an 8.9% confirmed response rate, as well as a 12.3% clinical benefit rate, defined as confirmed response or no disease progression for at least 6 months.

Tumor types associated with the highest confirmed response rates included endometrial cancer (20%), head and neck squamous cell carcinoma (19%) and cervical cancer (10.5%).

Response in PIK3CA-mutant tumors varied as a function of tumor type, PIK3CA-mutant variant and taselisib dose, Jhaveri said.

“There is a need for better understanding of mechanisms of resistance,” Jhaveri said. “PI3K pathway reactivation may be a common mechanism."

“Strategies to improve targeted therapy of PIK3CA-mutant tumors may include combination therapies and development of isoform- and mutant-selective inhibitors with a higher therapeutic index,” she added. – by Mark Leiser



Jhaveri K, et al. Abstract CT046. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.


Disclosure s : The study was funded by F. Hoffmann-La Roche. Jhaveri reports relationships with ADC Therapeutics, AstraZeneca, Debio Pharmaceuticals, Genentech, Novartis and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.