FDA Approvals in Non-Hodgkin Lymphoma, Breast Cancer, GVHD, and Mesothelioma

In In The News by Barbara Jacoby

By: Kristi Rosa

From: onclive.com

FDA approvals in non-Hodgkin lymphoma, breast cancer, graft-versus-host disease, and mesothelioma, and a breakthrough therapy designation in cervical cancer.

The FDA has approved the R2 regimen of lenalidomide plus rituximab for use in patients with previously treated follicular lymphoma and marginal zone lymphoma.

The approval was primarily based on findings from the phase III AUGMENT trial, in which the R2 regimen reduced the risk of disease progression or death by 54% versus rituximab alone in patients with relapsed/refractory indolent non-Hodgkin lymphoma. The median progression-free survival, per independent review, was 39.4 months with R2 versus 14.1 months with rituximab alone, at a median follow-up of 28.3 months.

By investigator assessment, the median PFS was 25.3 months versus 14.3 months, respectively, and the overall response rate was also significantly improved with the combination. The ORR per independent review was 78% with R-squared compared with 53% with single-agent rituximab. The 78% ORR with R-squared included a 44% complete response rate and a 34% partial response rate.

Additionally, overall survival data across the entire population showed that the hazard ratio for OS was 0.61 at a median follow-up of 28.3 months. The 2-year OS rate was 93% for R2 and 87% for rituximab alone.


In breast cancer, the FDA approved the PI3K inhibitor alpelisib, known by the trade name Piqray, for use in combination with fulvestrant as a treatment for postmenopausal women, and men, with hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic disease following progression on or after an endocrine-based regimen. This is the first PI3K inhibitor approved by the agency for breast cancer.

The decision was based on data from the phase III SOLAR-1 trial. Among a subset of patients in the trial with PIK3CA mutations, the median progression-free survival by local assessment was 11.0 months for those on the alpelisib arm compared with 5.7 months for patients who received placebo plus fulvestrant.

These data, which were assessed after a median follow-up of 20 months, translated into a 35% reduction in the risk of progression or death, with a hazard ratio of 0.65 in favor of alpelisib. In patients without a PIK3CA mutation, there was no advantage to alpelisib on median PFS in patients without a PIK3CA mutation.

Moreover, the overall response rate in the PIK3CA-mutant cohort was 26.6% in the alpelisib/fulvestrant arm versus 12.8% in the placebo/fulvestrant arm. In the PIK3CA-mutant subgroup with measurable disease, the ORRs were 35.7% and 16.2%, respectively.

The therascreen PIK3CA RGQ PCR Kit was simultaneously approved as a companion diagnostic test to detect the PIK3CA mutation in a tissue and/or a liquid biopsy.


The FDA has approved ruxolitinib for the treatment of adult and pediatric patients 12 years of age and older with steroid-refractory acute graft-versus-host disease.

The approval is based on findings from the phase II REACH1 trial, which demonstrated that the combination of ruxolitinib with corticosteroids elicited a 57% overall response rate at day 28 in patients with steroid-refractory aGVHD, with a complete response rate of 31%.

In February 2019, the FDA added 3 months to the review period for a supplemental new drug application for this indication of the JAK1/2 inhibitor, making the new action date May 24, 2019. The extension period was to allow the agency to review additional data they had requested from Incyte, the developer of ruxolitinib.

Ruxolitinib was previously approved by the FDA as a treatment for patients with polycythemia vera who are intolerant of or have an inadequate response to hydroxyurea, as well as for the treatment of patients with intermediate or high-risk myelofibrosis.


In mesothelioma, the FDA has approved the NovoTTF-100L System in combination with pemetrexed and platinum-based chemotherapy for the frontline treatment of patients with unresectable, locally advanced or metastatic malignant pleural disease, marking the first treatment for this patient population in more than 15 years.

The decision is based on findings from the prospective, single-arm STELLAR trial, results of which showed that the median overall survival in patients with unresectable, locally advanced or metastatic MPM who received TTF plus chemotherapy was 18.2 months.

Specifically, data showed that the median OS was 21.2 months for patients with epithelioid MPM and 12.1 months for those with non-epithelioid MPM. Sixty-two percent of patients enrolled who used NovoTTF-100L plus chemotherapy were still alive at 1 year, and the disease control rate in patients with at least 1 follow-up CT scan performed was 97%. The partial response rate was 40%, the stable disease rate was 57%, and the progressive disease rate was 3%.

There was no increase in serious systemic adverse events with the combination of NovoTTF-100L and chemotherapy, and the most common device-related AE was mild-to-moderate skin irritation.


The FDA has granted a breakthrough therapy designation to the tumor-infiltrating lymphocyte therapy LN-145 for the treatment of patients with recurrent, metastatic, or persistent cervical cancer whose disease has progressed on or after chemotherapy.

The designation is based on results from the ongoing phase II innovaTIL-04 trial, updated results of which will be presented at the 2019 ASCO Annual Meeting. Data in an abstract released ahead of the conference showed that the TIL therapy had an overall response rate of 44% in patients with advanced cervical cancer.

The ongoing, open-label, multicenter phase trial accrued patients with advanced cervical cancer who received at least 1 line of chemotherapy. Of the 27 evaluable patients, additional data showed that the ORR included 1 complete response, 9 partial responses, and 2 unconfirmed partial responses. The disease control rate was 89%, and at a median follow-up of 3.5 months, 11 of the 12 responding patients maintained their response.

The manufacturing of LN-145 comprises a 22-day process, in which TILs are generated at GMP facilities from tumors that have been shipped from local sites where they were initially harvested. The final LN-145 TIL treatment is cryopreserved and shipped back from the GMP to the original site where the patient is being treated.