Our R&D programs are managed on a portfolio basis from early discovery through late-stage development and include a balance of early-stage and late-stage programs to support future growth. Our late stage R&D programs in Phase III development include both investigational compounds for initial indications and additional indications or formulations for marketed products. Spending on these programs represent approximately 35-45% of our annual R&D expenses in the last three years.  Opdivo  was the only investigational compound or marketed product that represented greater than 10% of our R&D expenses in the last three years. Our late-stage development programs could potentially have an impact on our revenue and earnings within the next few years if regulatory approvals are obtained and products are successfully commercialized. The following are the developments in our marketed products and our late-stage pipeline: Product and Pipeline Developments 51 Product Indication Date Developments Opdivo Melanoma August 2018 Approval in Japan for treatment of adjuvant melanoma. July 2018 EC approval for the adjuvant treatment of adult patients with involvement of lymph nodes or metastatic disease who have undergone complete resection. June 2018 Announced results from the Phase III CheckMate-238 trial evaluating  Opdivo versus  Yervoy in patients with stage IIIB/C or stage IV melanoma who are at high risk of recurrence following complete surgical resection demonstrated statistically longer recurrence-free survival for  Opdivo , the primary endpoint of the study, versus  Yervoy  at a minimum follow-up of 24 months across key subgroups, including disease stages and BRAF mutation status. Multiple Myeloma June/August 2018 Announced in June 2018 that the FDA lifted a partial clinical hold placed on CheckMate-602, a randomized, open-label Phase III study evaluating the addition of  Opdivo to pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. The decision follows consultation with the FDA and agreement on amendments to the study protocol. In August 2018, the Company discontinued further enrollment of this study following a futility analysis. NSCLC June 2018 Approval in China for the treatment of locally advanced or metastatic NSCLC after prior platinum- based chemotherapy in adult patients without EGFR or ALK genomic tumor aberrations. April 2018 Announced that the pivotal, randomized Phase III CheckMate-078 trial evaluating  Opdivo  versus docetaxel in a predominantly Chinese population with previously treated advanced NSCLC demonstrated superior overall survival benefit in the primary endpoint regardless of PD-L1 expression or tumor histology. SCCHN January 2019 Acceptance in China of sBLA filing for patients who had previously been treated for metastatic or recurrent SCCHN. April 2018 Announced two-year overall survival data from CheckMate-141, a Phase III study, evaluating Opdivo  compared with investigator’s choice chemotherapy (cetuximab, docetaxel or methotrexate) in patients with recurrent or metastatic SCCHN after failure on platinum-based therapy. SCLC October 2018 Announced topline results from the Phase III CheckMate-331 study did not meet its primary endpoint of overall survival with  Opdivo  versus chemotherapy in patients with previously treated relapsed SCLC. August 2018 FDA approval as the first and only IO treatment option for patients with metastatic SCLC whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy. Various August 2018 Approval in Japan for patients with MPM which has progressed after chemotherapy. August 2018 Approval in Japan of an every 2 week/30 minute infusion dose and administration schedule for Opdivo  in six indications. June 2018 Announced preliminary data from the ongoing PIVOT Phase I/II Study, which is evaluating the combination of  Opdivo  with Nektar's investigational medicine, NKTR-214. The preliminary results presented at the 2018 American Society of Clinical Oncology reported safety, efficacy and biomarker data for patients enrolled in the Phase I dose-escalation stage of the study and for the first patients consecutively enrolled in select dose expansion cohorts in Phase II. April 2018 EC approval of an every four-week (Q4W)  Opdivo dosing schedule of 480 mg infused over 60 minutes as an option for patients with advanced melanoma and previously treated RCC as well as the approval of a two-week  Opdivo  dosing option of 240 mg infused over 30 minutes to replace weight-based dosing for all six approved monotherapy indications in the EU. March 2018 FDA approval of the Company's sBLA to update  Opdivo  dosing to include 480 mg infused every four weeks for a majority of approved indications as well as a shorter 30 minute infusion across all approved indications.