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Bradley M. Haverkos, MD
Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”


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