FDA Approvals: LENVIMA, OPDIVO, TECENTRIQ+VENTANA Assay – Drug and Device Digest

FDA BRIEF: Week of May 16, 2016

FDA approved

LENVIMA® (lenvatinib) capsules

Eisai Inc. Woodcliff Lake, New Jersey, USA

INDICATION: in combination with everolimus for the treatment of patients with advanced Renal Cell Carcinima following one prior anti-angiogenic therapy.

REG PATHWAY: Supplemental NDA, approved prior to PDUFA goal date. Breakthrough Therapy Designation,  Priority Review

MECHANISM OF ACTION: Receptor tyrosine kinase (RTK) inhibitor, inhibits activities of vascular endothelial growth factor (VEGF) receptors, and other  RTKs implicated in pathogenic angiogenesis, tumor growth, and cancer progression


  • Single, multicenter study (n=153), advanced or metastatic RCC, previously received anti-angiogenic therapy; LENVIMA +everolimus vs LENVIMA monotherapy
  • Primary Endpoint: Investigator-assessed Progression Free Survival (PFS), RECIST 1.1
  • Median PFS: 14.6 mo. vs 5.5 mo.
  • Overall Survival: 25.5 mo. vs 15.4 mo.



  • Most common adverse reactions:  Diarrhea, fatigue, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis/oral inflammation, hypertension, peripheral edema, cough, abdominal pain, dyspnea, rash, decreased weight, bleeding events, and proteinuria.

OPDIVO  (nivolumab) injection

Bristol-Myers Squibb, Princeton, New Jersey, USA

INDICATION: Teatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin

REG. PATHWAY: Supplemental BLA for new Indication. Opdivo first approved in 2014.  Breakthrough Therapy Designation,   Orphan Drug status,  Priority Review, Accelerated Approval Program. Approved  prior to PDUFA goal date.

MECHANISM OF ACTION: Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Can contribute to inhibition of active T-cell immune surveillance of tumors.


  • Two open-label studies (n=95), OPDIVO as single agent, in patients with cHL after failure of autologous HSCT and post-transplantation brentuximab vedotin
  • Included patients regardless of their tumor PD-L1 status
  • Endpoints: Objective response rate (ORR)  by independent radiographic review committee, duration of response (DOR)
  • ORR= 65% (95% CI: 55%, 75%), 58% partial remission,  7% complete remission
  • Median time-to-response: 2.1 months (range: 0.7 to 5.7 months)
  • Median DOR : 8.7 months.
  • Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials


  • Most common adverse reactions: Fatigue, upper respiratory tract infection, cough, pyrexia,diarrhe
  • Additional common adverse reactions: Rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis
  • Immune-mediated adverse reactions: Rash, pneumonitis, hepatitis, hyperthyroidism, colitis
  • Serious adverse reactions:  Pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, rash
  • “Warning and Precaution” for complications of allogeneic HSCT


TECENTRIQ (atezolizumab) injection

 Genentech, San Francisco, California, USA

VENTANA  PD-L1 (SP142) assay 

Ventana Medical Systems, Tucson, Arizona, USA.

Positive UC tissue stained with PD-L1 (SP142) assay, 10x

INDICATION: Treatment of locally advanced or 4 metastatic urothelial carcinoma who:

  • Have disease progression during or following platinum-containing chemotherapy
  • Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy


  •  Urothelial carcinoma most common type of bladder cancer
  • 76,960 new cases of bladder cancer and 16,390 deaths from the disease in 2016
  • First FDA-approved PD-L1 inhibitor

REG PATHWAY: BLA. Breakthrough Therapy Designation, Priority Review, Accelerated Approval

MECHANISM OF ACTION:   Binds to PD-L1 and blocks interactions with both PD-1 and B7.1 receptors – releases inhibition of the immune response, including activation of the anti-tumor immune response.


  • Sngle, multicenter, open-label, two-cohort trial (n=310),   locally advanced or metastatic urothelial carcinoma
  • Tumor specimens evaluated prospectively using the Ventana PD-L1 (SP142) Assay
  • Primary Endpoint: Confirmed objective response rate (ORR) assessed by independent review facility (IRF) using RECIST v1.1 and duration of response (DOR).
  • All patients : 14.8% partial shrinkage of tumors, DOR 2.1->13.8 mo.
  • “Positive” for PD-L1 expression: 26% tumor response vs. 9.5% for “negative”
  • Continued approval contingent upon verification and description of clinical benefit in confirmatory trials


  • Most common side effects: Fatigue, decreased appetite, nausea, urinary tract infection, fever (pyrexia) and constipation
  • Potential to cause infection and serious side effects from immune system effect


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