On November 16, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported the presentation of preliminary clinical data from an ongoing Phase 1/2 trial of its investigational PARP inhibitor, pamiparib, in combination with radiation therapy (RT) and/or temozolomide (TMZ) in patients with newly diagnosed or recurrent/refractory (R/R) glioblastoma multiforme (GBM) (Press release, BeiGene, NOV 16, 2018, View Source;p=irol-newsArticle&ID=2377491 [SID1234531392]). These data are being presented at the 23rd Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO), being held November 15 to 18 in New Orleans, LA. Discovered by BeiGene scientists in Beijing, pamiparib is currently in Phase 3 trials globally and in China as a monotherapy and in Phase 1/2 trials in combination with chemotherapy or immunotherapy for a variety of solid tumors.

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"There are limited treatment options available for patients with newly diagnosed and recurrent/refractory glioblastoma. This trial was designed to evaluate the potential synergies between DNA damaging therapies and/or agents and our investigational PARP inhibitor, pamiparib, which in pre-clinical studies has demonstrated brain penetration and PARP trapping activity. We are excited to continue to assess the potential of pamiparib combinations for a variety of difficult-to-treat cancers where there is urgent global need," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology at BeiGene.

"While response data are still maturing, these preliminary results demonstrated signs of antitumor activity of pamiparib in combination with radiation therapy in patients with newly diagnosed glioblastoma, as well as in combination with low-dose TMZ in patients with recurrent/refractory glioblastoma including those who previously progressed on TMZ, and support the continued development of these combinations," said Kent Shih, M.D., Senior Investigator of the Neuro-Oncology Program at Sarah Cannon Research Institute.

Summary of Preliminary Results

This open-label, multi-center global Phase 1b/2 multiple-dose and dose-escalation trial of pamiparib plus RT and/or TMZ (NCT03150862) was designed to evaluate the safety, efficacy and clinical activity of the combination in patients with newly diagnosed or R/R GBM. Patients with newly diagnosed GBM with unmethylated MGMT promoter status (Arm A) received pamiparib (60 mg twice a day) over escalating time periods (two, four, or six weeks) in combination with RT over six to seven weeks. Patients with R/R GBM (Arm C) received pamiparib (60 mg twice a day) continuously plus TMZ administered on Days 1 to 21 of each 28-day cycle. After evaluation of safety and tolerability from Arm A and C, Arm B will enroll patients with newly diagnosed GBM and treat them with the triple combination of RT, pamiparib, and TMZ.

As of September 14, 2018, a total of 18 patients with newly diagnosed GBM were enrolled in Arm A (n=3, 6 and 9 in the two-, four-, and six-week cohorts respectively). The median study follow-up duration is 19 weeks (2-54). Five grade >3 adverse events (AE) (chills, diarrhea, fatigue, nausea, vertigo, one [5.6%] each) were considered related to pamiparib or RT. Dose-limiting toxicities of fatigue, vertigo, and chills (one each) were reported.

As of the data cutoff date, 15 of the 18 patients were evaluable for response per modified response assessment in neuro-oncology (mRANO) criteria. Two of 15 patients achieved a partial response (PR, one was confirmed) and six patients achieved stable disease (SD); the disease control rate was 53.3% (95% CI: 26.6-78.7).

In Arm C, eight patients received TMZ at a fixed dose of 40 mg for 21 of 28 days and seven patients received 20 mg TMZ. The median study follow-up duration is 12.9 weeks (0.3-31.4). Grade >3 AEs included anemia (20%), fatigue (13.3%), and decreased lymphocyte (13.3%), which were considered related to pamiparib or TMZ. Dose-limiting toxicities of nausea and neutropenia were reported. The combination of 21 days of 40 mg TMZ with pamiparib was not tolerable; a lower 20 mg TMZ dose evaluation in combination with pamiparib is ongoing.

Ten of the 15 patients were evaluable per mRANO criteria and there were two PRs (one unconfirmed and one confirmed after data cutoff) and three SD.

About Glioblastoma Multiforme
Glioblastoma multiforme, also called glioblastoma, is an aggressive type of cancer where malignant grade IV tumors occur in the brain or spinal cord.2 These are the most common type of malignant brain tumors among adults.3 Symptoms include worsening headaches, nausea, vomiting and seizures. Patients can also present with neurological symptoms which are dependent on the tumor location (for example, weakness or sensory changes of face, arm or leg, balance difficulties and neurocognitive/memory issues).4 Glioblastoma can occur at any age but tends to occur more often in older adults. The five-year relative survival rates for patients with glioblastoma are: 19 percent (age 20-44), eight percent (age 44-54), and five percent (age 55-64).5

About Pamiparib
Pamiparib (BGB-290) is an investigational inhibitor of PARP1 and PARP2 which has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models. Discovered by BeiGene scientists in Beijing, pamiparib is currently in global clinical development as a monotherapy and in combination with other agents for a variety of solid tumor malignancies.