A Study to Investigate the Safety and Efficacy of Elsubrutinib and Upadacitinib Given Alone or in Combination in Participants With Moderately to Severely Active Systemic Lupus Erythematosus (SLE)

* Participant has clinical diagnosis of Systemic Lupus Erythematosus (SLE) at least 24 weeks prior to Screening, meeting at least 4 of the 11 revised Criteria for Classification of SLE according to the 1997 Update of the 1982 American College of Rheumatology (ACR) OR meeting at least 4 of the 2012 SLICC classification criteria, including at least 1 clinical criterion and 1 immunologic criterion. * At Screening, must have at least one of the following: * antinuclear antibody (ANA)+ (titer ≥ 1:80) * anti-dsDNA+ * anti-Smith+ * SLEDAI-2K (SLE Disease Activity Index) ≥ 6 despite background therapy as reported and independently adjudicated (clinical score ≥ 4, excluding lupus headache and/or organic brain syndrome) at Screening: * If 4 points of the required entry points are for arthritis, there must also be a minimum of 3 tender and 3 swollen joints. * If participant has rash and Principal Investigator (PI) considers it to be attributable to SLE, participant must consent to skin photograph collection for adjudication. * Score must be re-confirmed at the Baseline visit. * Physician's Global Assessment (PhGA) ≥ 1 during screening period. * Must be on background treatment, stable for 30 days prior to Baseline and throughout the study with antimalarial(s), prednisone (or prednisone equivalent) (≤ 20 mg), azathioprine (≤ 150 mg), mycophenolate (\<2 g), leflunomide (≤ 20 mg), cyclosporine, tacrolimus, and/or methotrexate (MTX) (≤ 20 mg). * No combinations of the above with immunomodulators other than prednisone (or equivalents) and antimalarials.

\- Participant using intravenous (IV) or intramuscular (IM) corticosteroids greater than or equal to a 40 mg prednisone-equivalent bolus within 30 days of planned randomization.