A phase 3 study to evaluate efficacy and safety of VYD222, an IgG1 monoclonal antibody for prevention of COVID-19 (CANOPY): Subset analysis of participants with significant immune compromise in the setting of solid tumor or hematologic malignancies.

2532 Background: CANOPY (NCT06039449) is a Phase 3 study to evaluate the efficacy and safety of VYD222 for prevention of COVID-19. VYD222 is a fully human IgG1 mAb demonstrating in vitro neutralizing activity across several SARS-CoV-2 variants of concern, including JN.1, the dominant variant in the U.S. as of Jan 2024, as well as HV.1, BA.2.86, XBB.1.5.10/EG.5, and HK.3. Methods: Here we describe a subset of participants in the single-arm, open label Cohort A of CANOPY, who were considered to have significant immune compromise due to active treatment for solid tumor or hematologic malignancies or a diagnosis of acute leukemia, chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, or multiple myeloma (regardless of treatment). Endpoints included safety and tolerability of VYD222 and evaluation of protection against COVID-19 based on calculated serum virus neutralizing antibody (sVNA) titers against SARS-CoV-2 after receiving VYD222. All Cohort A participants received 4500 mg IV of VYD222 on Day 1 and received the same dose at the Month 3 visit. Safety and tolerability were assessed as incidence of treatment emergent adverse events, including serious adverse events. Calculated sVNA levels were assessed for those participants who had serum concentration results at Day 28. Results: A total of 306 participants were enrolled in Cohort A. Of those, 55 (18%) were included in the solid tumor or hematologic malignancies subset. Median age was 65 years. 20 (36%) participants were being actively treated for solid tumor or hematologic malignancy, and 40 (73%) had one of the cancer diagnoses listed above; 29 (53%) participants had CLL. As of this data cut utilized for EUA submission, no participants in this open-label subset had RT-PCR confirmed symptomatic COVID-19, and two of 55 (3.6%) participants experienced adverse events (tachycardia, fatigue/night sweats) related to study drug. In both cases these adverse events occurred with administration of the first dose, were considered mild, resolved without treatment, did not cause discontinuation of study drug, and were not observed with the Month 3 dose administered. Safety data from the second dose in all patients in this subset was not yet available as of this analysis. In Cohort A overall and in participants in this subset with available data, VYD222 provided high calculated sVNA titers at Day 28 against a broad range of relevant SARS-CoV-2 variants of interest, including JN.1 and other recently circulating omicron subvariants. Conclusions: VYD222 4500 mg IV was well tolerated in a subset of adult participants with solid tumor or hematologic malignancies. VYD222 produced high calculated sVNA titer levels against SARS-CoV-2 variants of interest. Clinical trial information: NCT06039449 .