September 26, 2018 - Episode 1

FDA Approval in CLL and FL, Partial Hold Lifted in Tazemetostat Trials, and 2019 WCLC Conference Highlights


An FDA approval in chronic lymphocytic leukemia and follicular lymphoma, an FDA partial clinical hold lifted on an investigational agent, and highlights from the 19th World Conference on Lung Cancer Conference.

Welcome to OncLive News Network! I’m Gina Columbus.

The FDA has approved duvelisib, known by the trade name Copiktra, for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or relapsed/refractory follicular lymphoma.

The CLL/SLL indication is a standard approval and the follicular lymphoma indication is an accelerated approval that is contingent on the results of a confirmatory trial. Both indications are for the treatment of patients who have received at least 2 prior therapies.

The decision is based on data from the phase III DUO trial and the phase II DYNAMO study. In DUO, duvelisib reduced the risk of disease progression or death by 60% versus ofatumumab in patients with relapsed/refractory CLL/SLL who had received at least 2 prior lines of therapy. The median progression-free survival was 16.4 months with duvelisib versus 9.1 months with ofatumumab.

In DYNAMO, duvelisib demonstrated an overall response rate of 42% in patients with follicular lymphoma.

The FDA label for duvelisib includes a boxed warning regarding the potential risk of infections, diarrhea or colitis, cutaneous reactions, and pneumonitis in patients receiving the drug.

Verastem Oncology, the manufacturer of duvelisib, stated that it is implementing an informational Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on this treatment.


The FDA has lifted a partial clinical hold on tazemetostat trials, which reopened enrollment to studies examining the EZH2 inhibitor in patients with various solid tumors and hematologic malignancies.

The agency had placed the hold on the tazemetostat program after Epizyme, the manufacturer of the drug, provided a safety update detailing a pediatric patient with advanced poorly differentiated chordoma enrolled in a phase I trial who developed a secondary T-cell lymphoma.

At the time of the safety update, the patient was enrolled on the trial for approximately 15 months and had reached a confirmed partial response. Following the diagnosis of the secondary malignancy, the patient discontinued treatment with tazemetostat and received therapy for T-cell lymphoma.

In a news release announcing the hold lift, Epizyme reported that an independent panel of experts had validated the efficacy and safety findings across all tazemetostat trials.

Additionally, Epizyme noted that its official response to the FDA also included a thorough analysis of the potential link between tazemetostat and secondary malignancies.

In June 2017, the FDA granted orphan drug designation to tazemetostat for the treatment of adult patients with INI1-negative epithelioid sarcoma.


The 19th World Conference on Lung Cancer was held this past week in Toronto, Canada, providing the latest updates in the lung cancer landscape.

For example, an update to the phase III PACIFIC trial demonstrated that durvalumab induced a clinically meaningful improvement in overall survival compared with placebo in patients with stage III, unresectable non—small cell lung cancer who have not progressed following chemoradiotherapy.

Patients treated with the PD-L1 inhibitor after chemoradiotherapy had a 24-month OS rate of 66.3% versus 55.6% in patients who received placebo. The median OS was not reached in the durvalumab group and was 28.7 months in the placebo arm.

At the first planned interim analysis of the trial, the investigators observed an 11.2-month improvement in PFS with durvalumab versus placebo. As of March 22, 2018, median follow-up was 25.2 months.

With the longer follow-up, the median PFS by blinded independent central review was 17.2 months with durvalumab and 5.6 months in the placebo arm.

Durvalumab was also found to improve secondary endpoints, including time to death or distant metastasis, time to second progression, and safety.


Also at the meeting, phase II data showed that poziotinib has high antitumor activity in patients with metastatic, heavily pretreated EGFR and HER2 exon 20 mutant non—small cell lung cancer.

The agent specifically induced a best response rate of 55%, including a 43% confirmed objective response rate among evaluable patients with EGFR exon 20 mutant NSCLC in the study.

In the HER2 exon 20 cohort, the ORR was 50%, with a 42% confirmed ORR. Among all 13 patients in this arm, PFS was 5.1 months. Five patients remained on treatment at the data cutoff.

Poziotinib is a novel, orally available quinazoline-based tyrosine kinase inhibitor that irreversibly blocks signaling through the HER family of tyrosine kinase receptors and EGFR and HER2 mutations. In turn, this can lead to blocking of downstream signaling and inhibition of the proliferation of tumor cells.

Moreover, 56% of patients experienced grade 3/4 treatment-related adverse events, which led to dose reductions in 38 patients and treatment discontinuation in 2. The most common grade 3/4 events included skin rash and diarrhea.


Interim findings of the phase III IMpower132 trial presented at the conference showed that the addition of atezolizumab to carboplatin/cisplatin in the first-line setting and to pemetrexed as maintenance therapy significantly improved progression free survival in patients with stage IV nonsquamous non—small cell lung cancer.

The regimen led to a 40% reduction in the risk of disease worsening or death versus chemotherapy alone, with a median progression-free survival at 7.6 versus 5.2 months, respectively.

The global, randomized, open-label, phase III IMpower132 study evaluated the efficacy and safety of this combination in 578 chemotherapy-naïve patients with stage IV nonsquamous NSCLC, without EGFR or ALK genetic alterations.

The PFS benefit was observed across key clinical subgroups, including Asian patients, never smokers, and current and former smokers.

Moreover, the atezolizumab regimen improved OS by 4.5 months over pemetrexed-based chemotherapy alone at 18.1 versus 13.6 months. However, the difference was not statistically significant. These data will not be finalized until next year.


In small cell lung cancer, the phase III IMpower133 trial data, presented at the WCLC conference, demonstrated the addition of atezolizumab to standard carboplatin and etoposide in the frontline setting significantly prolonged survival in patients with extensive-stage disease versus chemotherapy alone.

This is the first study in 20 years to show a clinically meaningful improvement in overall survival over the current standard of care in frontline extensive-stage SCLC.

After a median follow-up of 13.9 months, median OS was 12.3 months in the atezolizumab arm compared with 10.3 months in the placebo arms, which led to a 30% reduction in the risk of death. OS events occurred in 51.7% of the atezolizumab arm and 66.3% of the control arm.

Median PFS was 5.2 months in the atezolizumab group versus 4.3 months in the placebo group. Atezolizumab was associated with a higher 6-month PFS rate, and a more than doubling 12-month PFS rate compared with placebo.

The investigators saw no major difference in ORR between arms or in median duration of response.


This week, we sat down with Dr Gregory J. Riely, of Memorial Sloan Kettering Cancer Center, to discuss communicating goals of molecular testing in non—small cell lung cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.