Revised DLT criteria • Revised eligibility criterion for recovery from toxicity from previous immunotherapy treatment • Added a criterion for dose delay due to non-immune-related adverse events (AEs). • The split first dose of daratumumab was replaced with the full daratumumab 16 milligrams per kilogram (mg/kg) regimen. • Clarified that communication with health authorities will occur before proceeding to Part 3. • Added a new section regarding study termination for safety considerations.

On 25 May 2018, the sponsor stopped further enrollment into this study, Study 54767414MMY2036, based on safety and efficacy findings in the Study 54767414LUC2001, which combined daratumumab with atezolizumab in non-small cell lung cancer. At the third planned DMC review on 23 May 2018, the DMC reviewed the subject data for the Study 54767414LUC2001. The data monitoring committee (DMC) determined that there was no observed benefit in combination treatment arm (daratumumab+atezolizumab) over atezolizumab alone and recommended stopping enrollment of the study. In addition, the DMC recommended discontinuation of daratumumab treatment to all subjects receiving combination therapy (subjects randomized to the combination Arm B, and subjects randomized to Arm A who had crossed over into Arm B). Although no unexpected imbalances in on-treatment toxicities were observed, the DMC noted a clear early difference in number of deaths between atezolizumab monotherapy arm and combination arm. Discrepancy was observed within first 3 months of start of treatment, where the number of deaths were 4 in the atezolizumab arm and 10 in the combination arm, giving rise to 3-month survival rates of 90.7 percent (%) for the atezolizumab arm and 76.2% for the combination arm. Since the benefit/risk ratio changed for combination therapy in Study 54767414LUC2001, sponsor decided to suspend enrollment into other studies that combine daratumumab and a programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) regardless of indication. In addition to discontinuing enrollment in this study, treatment with the combination of daratumumab and JNJ-63723283 was discontinued and ongoing subjects were given the option to continue on daratumumab monotherapy until subject met one or more of the treatment discontinuation criteria. Assessments and data collection for the new daratumumab monotherapy period were defined and a window for End-of-Treatment (EOT) visit was added.

The overall reason for the amendment was to provide flexibility for study investigators to prioritize the safety of their subjects during the global coronavirus (COVID-19) pandemic. To ensure continuity of study treatment, while limiting subjects’ time spent at the study center, for subjects who will continue to receive daratumumab intravenous (IV), the duration of infusion may be shortened starting in Cycle 2 onwards to a 90-minute infusion for subjects without a history of an infusion related reaction after the third dose, at the discretion of the investigator. Detailed information regarding daratumumab IV administration, including infusion rates and duration, is removed and will be provided only in the Site Investigational Product Procedures Manual (SIPPM)’.