Cancer
Conditions
Keywords
COVID-19, Booster
Brief summary
The goal of this study is to assess the safety and effectiveness of COVID vaccine booster doses in patients with cancer who have not developed an antibody after the U.S. Food and Drug Administration (FDA) Emergency Use Authorized COVID primary vaccination series.
Detailed description
Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering 'booster' doses of COVID-19 vaccines beyond the standard two-dose series, for this group of patients. Therefore, studying the efficacy of these additional vaccine doses against SARS-CoV-2 and variants of concern is of utmost importance in this immunocompromised patient population. The investigator team designed a prospective single arm clinical trial for consenting patients with cancer who had received two doses of mRNA, or one dose of AD26.CoV2.S vaccine, and were administered a third dose of mRNA vaccine. Patients who had no or low responses to three mRNA COVID vaccines were administered a fourth dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity, and neutralization activity, at baseline and 4 weeks. First Booster Dose (3rd dose) study: Following the informed consent process patients are enrolled into the study. After drawing baseline laboratory samples that include spike antibody, a sample for T-cell assay, and a biobank sample, patients will receive a third mRNA vaccine (initially BNT162b2 per protocol, later amended to allow for a third mRNA-1273 vaccine after the Food and Drug Administration \[FDA\] authorized 'booster' doses in the fall of 2021). Patients who had received Ad26.CoV2.S vaccine will receive a BNT162b2 booster vaccine. Follow-up visits are scheduled at \ 4 weeks and 4-6 months following the booster dose and laboratory sample collections will be repeated. Second Booster Dose (4th dose) study: For patients who did not seroconvert after three doses or had low antibody response (\<1000 AU/mL as determined by in-house Abbott assay), it was hypothesized that a 'mix and match' strategy with a 2nd booster dose (4th dose) of COVID-19 vaccine would induce seroconversion and improve boosting of humoral antibody responses. To study this, a protocol was designed wherein patients who had received their 1st booster dose (3rd dose) of mRNA vaccines and had undetectable anti-S antibody or had an anti-S antibody level of \<1000 AU/mL measured at least 14 days after third dose would be randomized to an mRNA vs. adenoviral booster (4th) vaccine dose. Responses would be then assessed at 4 weeks after the 2nd booster dose (4th dose) through measurement of anti-S antibody results. Complete blood counts (CBC), quantitative immunoglobulin levels (IgG, IgA, and IgM), lymphocyte subsets, T-cell responses, and neutralization activity at baseline and 4 weeks will be assessed for each of these patients. Following the implementation of this protocol, the Centers for Disease Control (CDC) published a statement that advised that the mRNA vaccines should be preferentially administered over the adenoviral vaccines given concern over rare side effects such as thrombocytopenia and thrombosis syndrome. Given this advisory, the protocol was amended to allow recruitment in a cohort that would receive a fourth dose of the BNT162b2 vaccine to comply with CDC guidelines.
Interventions
BIOLOGICALBNT162b2 vaccine
Administer an additional dose of the BNT162b2 mRNA vaccine to patients with cancer who have a negative SARS-CoV-2 Spike IgG at least 14 days after 2 doses of the mRNA vaccines (BNT162b2/mRNA-1273) or 28 days after the adenoviral based Ad26CoV2.S vaccine.
Sponsors
Albert Einstein College of Medicine
National Cancer Institute (NCI)
The Leukemia and Lymphoma Society
Montefiore Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Cohort 1): * Above the age of 18 * Meet one of the sub-criteria below: * Meet the CDC definition for immunocompromised status for cancer patients, i.e patients receiving active treatment for solid tumor or hematologic malignancy OR * Be a recipient of stem cell transplant or CAR-T cell therapy in the last 2 years OR * Have a negative SARS-CoV-2 spike IgG despite standard vaccination series, irrespective of active/inactive cancer status, on observation, or active therapy. * Underwent an in-person encounter at a study facility during the study period * Have received the second of the mRNA-based vaccines BNT162b2 and mRNA-1273 (Pfizer/BioNTech or Moderna, respectively) or one dose of the adenoviral Ad26CoV2.S (Johnson & Johnson) vaccine at least 28 days before the booster dose.
Exclusion criteria
(Cohort 1): * Patients who have had a serious adverse reaction to any prior COVID-19 vaccines resulting in emergency room visit or hospitalization, had events related to myocarditis, thrombosis and thrombocytopenia syndrome or anaphylaxis to any prior dose of the COVID-19 vaccines. * Patients who have had a documented COVID-19 infection in the 90 days prior to starting the study Inclusion Criteria (Cohort 2): * Above the age of 18 * Have a diagnosis of prior or active malignancy, either hematological or solid tumor * Have a negative or low-level SARS-CoV-2 spike IgG after 14 days of booster vaccination series irrespective of active/inactive cancer status, on observation, or active therapy. * Have received an FDA-authorized booster dose of mRNA (BNT162b2 and mRNA-1273) vaccine at least 28 days before study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations | 4 weeks after administration of 1st booster dose | Rate will be determined as the percentage of patients demonstrating booster-induced seroconversion, as evidenced by anti-Spike antibody testing, who were seronegative after the primary series of FDA authorized COVID-19 vaccinations. |
| Percentage of Patients Who Were 'Responders' After 2nd Booster Dose | 4 weeks after administration of 2nd booster dose | A patient was classified as a responder if they either (1) had positive anti-S antibody at 4 weeks if seronegative at baseline (following 1st booster dose) or (2) if they achieved a titer of \>1000 AU/mL at 4 weeks if they were sero-low at baseline (following 1st booster dose) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Anti-Spike Antibody Titer for Patients With Hematologic Malignancies | Baseline to 4 weeks after administration of 1st booster dose | The median change in anti-S antibody titer for patients with Hematologic malignancies was determined. |
| Change in Anti-Spike Antibody Titer for Patients With Solid Tumor Malignancies | Baseline to 4 weeks after administration of 1st booster dose | The median change in anti-S antibody titer for patients with Solid tumor malignancies was determined. |
| Change in Anti-Spike Antibody Titer Among Patients With Hematologic Malignancy by Type | Baseline to 4 weeks after administration of 1st booster dose | Median change in Anti-S antibody titers was determined in patients who presented with Hematologic (either Lymphoid or Myeloid) malignancies. |
| Percentage of Patients Seropositive/Seronegative Following 1st Booster Dose | 4 weeks after administration of 1st booster dose | Percentage of Patients who were either seropositive or seronegative following administration of 1st booster dose as demonstrated by anti-S antibody testing. |
| Neutralizing Antibodies Detected Among Seropositive Patients | 4 weeks after administration of 1st booster dose | The GenScript surrogate virus neutralization assay was used to analyze samples from seropositive patients to detect for the presence of neutralizing antibodies. The percentage of patients with neutralizing antibodies was determined. |
| Positive T-cell Response Among Patients With a Negative Anti-S Antibody | 4 weeks after administration of 1st booster dose | Percentage of patients with a negative anti-S antibody following 1st booster dose who demonstrated a Positive T-cell response. |
| Positive T-cell Response Among Patients With a Negative T-cell Response at Baseline | 4 weeks after administration of 1st booster dose | Percentage of patients who demonstrated a Positive T-cell response among those who demonstrated a negative T-cell response at baseline. |
| Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy Within 6 Months of Treatment | Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose | In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients on anti-CD20 antibody therapy within 6 months of administration of 1st booster dose. |
| Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy | Baseline to 4 weeks after administration of 1st booster dose | In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients on anti-CD20 antibody therapy just prior to the study. |
| Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy | Baseline to 4 weeks after administration of 1st booster dose | In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients not on anti-CD20 antibody therapy just prior to the study. |
| Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy Within 6 Months of Treatment | Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose | In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients not on anti-CD20 antibody therapy within 6 months of treatment |
| Percentage of Patients Who Remained Seropositive Following 1st Booster Dose | ~4-6 months after administration of 1st booster dose | Percentage of Patients who maintained a positive anti-S antibody (seropositive) following administration of 1st booster dose as demonstrated by anti-S antibody testing. |
| Positive Anti-Spike Antibody (IgG) Titer | 4 weeks after administration of 1st booster dose | The number of patients with evaluable T-cell immune responses who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 after 1st booster dose of vaccine. |
| Percentage of Patients With Low (Anti-S Antibody) Serum Antibodies | Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months | The percentage of patients with low serum antibodies before administration of the 2nd booster dose was determined by assay. Patients with anti-S antibody titers of \<1000 AU/mL were determined to have low serum antibodies. |
| Anti-spike IgG Responders After the 2nd Booster Dose | ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months | The percentage of patients who were classified as 'responders' after the 2nd Booster dose. A patient was classified as a responder if they: (1) had positive anti-S antibody at 4 weeks if seronegative after 1st booster dose or (2) if they achieved a titer of \>1000 AU/mL at 4 weeks if they were sero-low after 1st booster dose. |
| Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Remained Seronegative Following 1st Booster Dose | ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months | Rate was determined as the percentage of patients demonstrating booster-induced seroconversion to positive anti-S antibody who had remained seronegative following administration of Primary Vaccination series and 1st Booster dose of BNT162b2, mRNA-1273, or AdCoV2.S COVID vaccine. |
| Percentage of Patients With Low Anti-Spike Antibody Who Responded Following 2nd Booster Dose | ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months | The percentage of Patients with low anti-Spike antibody, determined to be IgG \<1000 AU/mL by assay, who responded following administration of 2nd booster dose. Responses in this context were determined to be those patients with assay results of IgG \> 1000 AU/mL. |
| Anti-Spike Antibody Titer Following Administration of 1st Booster Dose | Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months | The median Anti-S antibody titer following administration of the primary vaccination series and 1st booster dose in Cohort B was determined. |
| Anti-Spike Antibody Titer Following Administration of 2nd Booster Dose | ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months | The median Anti-S antibody titer following administration of the 2nd booster dose (Cohort B) was determined. |
| Positive Anti-Spike Antibody (IgG) Titer Prior to 2nd Booster Dose | Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months | The number of Cohort B patients with evaluable T-cell immune responses who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 following 1st booster dose and prior to 2nd booster dose of vaccine. |
| Positive Anti-Spike Antibody (IgG) Titer Following 2nd Booster Dose | ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months | The percentage of Cohort B patients who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 following administration of 2nd booster dose of vaccine. |
| Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Prior to 2nd Booster Dose | Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months | Neutralization activity against the WT variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported. |
| Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Following 2nd Booster Dose | ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months | Neutralization activity against the WT variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported. |
| Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Prior to 2nd Booster Dose | Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months | Neutralization activity against the Omicron BA.1 variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported. |
| Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Following 2nd Booster Dose | ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months | Neutralization activity against the Omicron BA.1 variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported. |
| Percentage of Seronegative Patients Before 2nd Booster Dose | Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months | The percentage of patients determined to be seronegative before 2nd booster dose |
| Spike Antibody Titer | 4 weeks after administration of 1st booster dose | The median SARS-CoV-2 spike antibody (IgG) titer among the entire cohort at 4 weeks after administration of the 1st booster dose of vaccine was determined. |
Countries
United States
Participant flow
Pre-assignment details
189 patients were assessed for eligibility to receive a booster COVID-19 vaccine after at least 28 days following completion of the standard COVID-19 vaccination series. Of the 189 patients, 56 patients declined to participate in the study, 2 patients did not meet eligibility criteria, and 25 participants were not enrolled due to 'Other reasons.' Accordingly, 106 patients were enrolled into the Booster Dose Trial.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Patients who have a negative SARS-CoV-2 spike IgG at least 14 days after 2 doses of the mRNA vaccines (BNT162b2 or mRNA-1273), or 28 days after the adenoviral based Ad26CoV2.S vaccine, received a third/booster mRNA vaccine (initially BNT162b2 per protocol, which was later amended to allow for third mRNA-1273 vaccine after the FDA authorized 'booster' doses in the fall of 2021). Patients then returned for follow-up at 4 weeks and 4-6 months after their third/booster dose | 106 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 1st Booster: 4-6 Month Follow up Visit | Lost to Follow-up | 59 |
| 2nd Booster: 4 Week Follow up Visit | Declined to Participate | 2 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 68 years |
| Cancer Status Active | 69 Participants |
| Cancer Status Progressive | 3 Participants |
| Cancer Status Recurrent | 3 Participants |
| Cancer Status Relapse | 7 Participants |
| Cancer Status Remission | 24 Participants |
| Hematologic Malignancy Lymphoid | 55 Participants |
| Hematologic Malignancy Myeloid | 11 Participants |
| Malignancy Category Hematologic Malignancy | 66 Participants |
| Malignancy Category Solid Tumor Malignancy | 40 Participants |
| Median Titer after Primary Vaccination Series | 212.1 AU/mL |
| On Treatment at the Time of Booster No | 26 Participants |
| On Treatment at the Time of Booster Yes | 80 Participants |
| Patients with evaluable positive T-cell immune responses who were seronegative for Anti-S antibody | 21 Participants |
| Patients with neutralizing antibodies (in seropositive patients) | 47 Participants |
| Percentage of Patients Seropositive/Seronegative at Baseline (before 1st booster dose) Seronegative Patients | 35 Participants |
| Percentage of Patients Seropositive/Seronegative at Baseline (before 1st booster dose) Seropositive Patients | 68 Participants |
| Positive Anti-spike IgG Titers among Patients with evaluable T-cell Results | 65 Participants |
| Previous Vaccine Administered Ad26.CoV2.S | 6 Participants |
| Previous Vaccine Administered BNT162b2 | 72 Participants |
| Previous Vaccine Administered mRNA-1273 | 28 Participants |
| Race/Ethnicity, Customized African-American | 33 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants |
| Race/Ethnicity, Customized Caucasian | 36 Participants |
| Race/Ethnicity, Customized Hispanic | 27 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Region of Enrollment United States | 106 participants |
| Sex: Female, Male Female | 58 Participants |
| Sex: Female, Male Male | 48 Participants |
| Type of Booster Vaccine BNT162b2 | 78 Participants |
| Type of Booster Vaccine mRNA-1273 | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 106 |
| other Total, other adverse events | 63 / 106 |
| serious Total, serious adverse events | 1 / 106 |
Outcome results
Primary
Percentage of Patients Who Were 'Responders' After 2nd Booster Dose
A patient was classified as a responder if they either (1) had positive anti-S antibody at 4 weeks if seronegative at baseline (following 1st booster dose) or (2) if they achieved a titer of \>1000 AU/mL at 4 weeks if they were sero-low at baseline (following 1st booster dose)
Time frame: 4 weeks after administration of 2nd booster dose
Population: 18 participants were enrolled into the 2nd booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Percentage of Patients Who Were 'Responders' After 2nd Booster Dose | 12 Participants |
Primary
Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations
Rate will be determined as the percentage of patients demonstrating booster-induced seroconversion, as evidenced by anti-Spike antibody testing, who were seronegative after the primary series of FDA authorized COVID-19 vaccinations.
Time frame: 4 weeks after administration of 1st booster dose
Population: 35 of 106 patients were seronegative after initial 2 dose vaccination series. At 4 weeks following receipt of the booster vaccine, 57% (20/35) of these patients seroconverted and had a detectable antibody response as demonstrated by anti-S antibody testing
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Were Seronegative After Primary Series of COVID-19 Vaccinations | 20 Participants |
Secondary
Anti-Spike Antibody Titer Following Administration of 1st Booster Dose
The median Anti-S antibody titer following administration of the primary vaccination series and 1st booster dose in Cohort B was determined.
Time frame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
Population: 18 participants were enrolled into the 2nd booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Anti-Spike Antibody Titer Following Administration of 1st Booster Dose | 131.1 AU/mL |
Secondary
Anti-Spike Antibody Titer Following Administration of 2nd Booster Dose
The median Anti-S antibody titer following administration of the 2nd booster dose (Cohort B) was determined.
Time frame: ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months
Population: 18 participants were enrolled into the 2nd booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Anti-Spike Antibody Titer Following Administration of 2nd Booster Dose | 1700 AU/mL |
Secondary
Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy
In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients not on anti-CD20 antibody therapy just prior to the study.
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 81 patients were not on Anti-CD20 antibody therapy just prior to the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy | 12735 AU/mL |
Secondary
Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy Within 6 Months of Treatment
In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients not on anti-CD20 antibody therapy within 6 months of treatment
Time frame: Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose
Population: 81 patients were not on Anti-CD20 antibody therapy within 6 months prior to treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Anti-spike Antibody Titers for Patients Not on Anti-CD20 Antibody Therapy Within 6 Months of Treatment | 587 AU/mL |
Secondary
Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy
In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients on anti-CD20 antibody therapy just prior to the study.
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 25 patients were on Anti-CD20 antibody therapy just prior to the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy | 0 AU/mL |
Secondary
Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy Within 6 Months of Treatment
In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were assessed for patients on anti-CD20 antibody therapy within 6 months of administration of 1st booster dose.
Time frame: Within 6 months prior to treatment to 4 weeks after administration of 1st booster dose
Population: 25 patients were on Anti-CD20 antibody therapy within 6 months of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Anti-spike Antibody Titers for Patients on Anti-CD20 Antibody Therapy Within 6 Months of Treatment | 0 AU/mL |
Secondary
Anti-spike IgG Responders After the 2nd Booster Dose
The percentage of patients who were classified as 'responders' after the 2nd Booster dose. A patient was classified as a responder if they: (1) had positive anti-S antibody at 4 weeks if seronegative after 1st booster dose or (2) if they achieved a titer of \>1000 AU/mL at 4 weeks if they were sero-low after 1st booster dose.
Time frame: ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months
Population: 18 participants were enrolled into the second booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Anti-spike IgG Responders After the 2nd Booster Dose | 12 Participants |
Secondary
Change in Anti-Spike Antibody Titer Among Patients With Hematologic Malignancy by Type
Median change in Anti-S antibody titers was determined in patients who presented with Hematologic (either Lymphoid or Myeloid) malignancies.
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: Of patients with Hematologic malignancies, 55 patients had Lymphoid malignancies and 11 patients had Myeloid malignancies
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1st Booster Dose | Change in Anti-Spike Antibody Titer Among Patients With Hematologic Malignancy by Type | Lymphoid Malignancies | 1169 AU/mL |
| 1st Booster Dose | Change in Anti-Spike Antibody Titer Among Patients With Hematologic Malignancy by Type | Myeloid Malignancies | 9424 AU/mL |
Secondary
Change in Anti-Spike Antibody Titer for Patients With Hematologic Malignancies
The median change in anti-S antibody titer for patients with Hematologic malignancies was determined.
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 66 patients had Hematologic malignancies
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Change in Anti-Spike Antibody Titer for Patients With Hematologic Malignancies | 2167 AU/mL |
Secondary
Change in Anti-Spike Antibody Titer for Patients With Solid Tumor Malignancies
The median change in anti-S antibody titer for patients with Solid tumor malignancies was determined.
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 40 patients had Solid Tumor malignancies
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Change in Anti-Spike Antibody Titer for Patients With Solid Tumor Malignancies | 31010 AU/mL |
Secondary
Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Following 2nd Booster Dose
Neutralization activity against the Omicron BA.1 variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported.
Time frame: ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months
Population: 18 participants were enrolled into the 2nd booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1st Booster Dose | Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Following 2nd Booster Dose | Positive | 6 Participants |
| 1st Booster Dose | Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Following 2nd Booster Dose | Negative | 12 Participants |
Secondary
Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Prior to 2nd Booster Dose
Neutralization activity against the Omicron BA.1 variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported.
Time frame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
Population: 18 participants were enrolled into the 2nd booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1st Booster Dose | Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Prior to 2nd Booster Dose | Positive | 0 Participants |
| 1st Booster Dose | Neutralization Against Omicron BA.1 SARS-CoV-2 Variant Prior to 2nd Booster Dose | Negative | 18 Participants |
Secondary
Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Following 2nd Booster Dose
Neutralization activity against the WT variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported.
Time frame: ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months
Population: 18 participants were enrolled into the 2nd booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1st Booster Dose | Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Following 2nd Booster Dose | Positive | 13 Participants |
| 1st Booster Dose | Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Following 2nd Booster Dose | Negative | 5 Participants |
Secondary
Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Prior to 2nd Booster Dose
Neutralization activity against the WT variant was assessed using a neutralization activity assay. The percentage of patients with positive and negative T-cell results are reported.
Time frame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
Population: 18 participants were enrolled into the 2nd booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1st Booster Dose | Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Prior to 2nd Booster Dose | Positive | 12 Participants |
| 1st Booster Dose | Neutralization Against Wildtype (WT) SARS-CoV-2 Variant Prior to 2nd Booster Dose | Negative | 6 Participants |
Secondary
Neutralizing Antibodies Detected Among Seropositive Patients
The GenScript surrogate virus neutralization assay was used to analyze samples from seropositive patients to detect for the presence of neutralizing antibodies. The percentage of patients with neutralizing antibodies was determined.
Time frame: 4 weeks after administration of 1st booster dose
Population: 85 patients were seropositive at 4 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Neutralizing Antibodies Detected Among Seropositive Patients | 77 Participants |
Secondary
Percentage of Patients Seropositive/Seronegative Following 1st Booster Dose
Percentage of Patients who were either seropositive or seronegative following administration of 1st booster dose as demonstrated by anti-S antibody testing.
Time frame: 4 weeks after administration of 1st booster dose
Population: 4 week samples were not collected/processed from 6 patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1st Booster Dose | Percentage of Patients Seropositive/Seronegative Following 1st Booster Dose | Seropositive Patients | 85 Participants |
| 1st Booster Dose | Percentage of Patients Seropositive/Seronegative Following 1st Booster Dose | Seronegative Patients | 15 Participants |
Secondary
Percentage of Patients Who Remained Seropositive Following 1st Booster Dose
Percentage of Patients who maintained a positive anti-S antibody (seropositive) following administration of 1st booster dose as demonstrated by anti-S antibody testing.
Time frame: ~4-6 months after administration of 1st booster dose
Population: 47 patients completed their 4-6 month follow-up visit following 1st booster dose. All 47 were seropositive at 4 weeks. 36 of these patients had hematologic malignancies and 11 of these patients had solid malignancies. Six patients had received anti-COVID monoclonal antibody therapy as per standard of care between the 4 week and 4-6 months' follow-up period. Nine patients had received a fourth dose of COVID-19 vaccine outside of the context of the study prior to the time of 4-6 months' follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Percentage of Patients Who Remained Seropositive Following 1st Booster Dose | 47 Participants |
Secondary
Percentage of Patients With Low (Anti-S Antibody) Serum Antibodies
The percentage of patients with low serum antibodies before administration of the 2nd booster dose was determined by assay. Patients with anti-S antibody titers of \<1000 AU/mL were determined to have low serum antibodies.
Time frame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
Population: 18 participants were enrolled into the second booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Percentage of Patients With Low (Anti-S Antibody) Serum Antibodies | 11 Participants |
Secondary
Percentage of Patients With Low Anti-Spike Antibody Who Responded Following 2nd Booster Dose
The percentage of Patients with low anti-Spike antibody, determined to be IgG \<1000 AU/mL by assay, who responded following administration of 2nd booster dose. Responses in this context were determined to be those patients with assay results of IgG \> 1000 AU/mL.
Time frame: ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months
Population: 11 patients were sero-low (IgG \<1000 AU/mL) prior to administration of 2nd booster dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Percentage of Patients With Low Anti-Spike Antibody Who Responded Following 2nd Booster Dose | 11 Participants |
Secondary
Percentage of Seronegative Patients Before 2nd Booster Dose
The percentage of patients determined to be seronegative before 2nd booster dose
Time frame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
Population: 18 participants were enrolled into the second booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Percentage of Seronegative Patients Before 2nd Booster Dose | 7 Participants |
Secondary
Positive Anti-Spike Antibody (IgG) Titer
The number of patients with evaluable T-cell immune responses who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 after 1st booster dose of vaccine.
Time frame: 4 weeks after administration of 1st booster dose
Population: 89 patients had evaluable T-cell results at 4 weeks following 1st booster dose of vaccine
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Positive Anti-Spike Antibody (IgG) Titer | 76 Participants |
Secondary
Positive Anti-Spike Antibody (IgG) Titer Following 2nd Booster Dose
The percentage of Cohort B patients who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 following administration of 2nd booster dose of vaccine.
Time frame: ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months
Population: 18 participants were enrolled into the 2nd booster dose cohort. All 18 patients in this cohort had hematologic malignancies. 15 patients received BNT162b2 as their 2nd booster vaccine and 3 patients received Ad26.CoV2.S as their 2nd booster vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Positive Anti-Spike Antibody (IgG) Titer Following 2nd Booster Dose | 17 Participants |
Secondary
Positive Anti-Spike Antibody (IgG) Titer Prior to 2nd Booster Dose
The number of Cohort B patients with evaluable T-cell immune responses who demonstrated positive anti-S antibody (IgG) titers against SARS-CoV-2 following 1st booster dose and prior to 2nd booster dose of vaccine.
Time frame: Prior to administration of 2nd booster dose, a minimum of 14-28 days following 1st booster dose, a median of approximately 5 months
Population: 14 patients in Cohort B had evaluable T-cell responses
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Positive Anti-Spike Antibody (IgG) Titer Prior to 2nd Booster Dose | 11 Participants |
Secondary
Positive T-cell Response Among Patients With a Negative Anti-S Antibody
Percentage of patients with a negative anti-S antibody following 1st booster dose who demonstrated a Positive T-cell response.
Time frame: 4 weeks after administration of 1st booster dose
Population: 15 patients had a negative anti-S antibody result at 4 weeks following booster dose administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Positive T-cell Response Among Patients With a Negative Anti-S Antibody | 11 Participants |
Secondary
Positive T-cell Response Among Patients With a Negative T-cell Response at Baseline
Percentage of patients who demonstrated a Positive T-cell response among those who demonstrated a negative T-cell response at baseline.
Time frame: 4 weeks after administration of 1st booster dose
Population: 21 patients demonstrated a negative T-cell response against SARS-CoV-2 at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Positive T-cell Response Among Patients With a Negative T-cell Response at Baseline | 14 Participants |
Secondary
Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Remained Seronegative Following 1st Booster Dose
Rate was determined as the percentage of patients demonstrating booster-induced seroconversion to positive anti-S antibody who had remained seronegative following administration of Primary Vaccination series and 1st Booster dose of BNT162b2, mRNA-1273, or AdCoV2.S COVID vaccine.
Time frame: ~4 weeks after administration of 2nd booster dose, a minimum of 4-6 weeks following 1st booster dose, a median of approximately 6.0-6.5 months
Population: 7 patients remained seronegative following administration of Primary vaccination series and 1st booster dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Rate of Seroconversion for SARS-CoV-2 Spike Antibody Among Patients Who Remained Seronegative Following 1st Booster Dose | 2 Participants |
Secondary
Spike Antibody Titer
The median SARS-CoV-2 spike antibody (IgG) titer among the entire cohort at 4 weeks after administration of the 1st booster dose of vaccine was determined.
Time frame: 4 weeks after administration of 1st booster dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Spike Antibody Titer | 9997 AU/mL |
Post Hoc
Anti-spike Antibody Titers for Patients Not on Bruton's Tyrosine Kinase (BTK) Inhibitors
In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were determined for patients not on BTK inhibitors prior to the study
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 94 patients were not on BTK inhibitors prior to the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Anti-spike Antibody Titers for Patients Not on Bruton's Tyrosine Kinase (BTK) Inhibitors | 9355 AU/mL |
Post Hoc
Anti-spike Antibody Titers for Patients on Bruton's Tyrosine Kinase (BTK) Inhibitors
In order to determine association of specific cancer-directed therapies with the booster effect, median change in anti-S antibody titers were determined for patients on BTK inhibitors prior to the study
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 12 patients were on BTK inhibitors prior to the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1st Booster Dose | Anti-spike Antibody Titers for Patients on Bruton's Tyrosine Kinase (BTK) Inhibitors | 0 AU/mL |
Post Hoc
Change in Anti-Spike Antibody Titer Based on Type of Booster Administered
Median change in anti-S antibody titer was determined based on the type of booster administered (BNT162b2 or mRNA-1273)
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 78 patients were administered the BNT162b2 booster and 28 patients were administered the mRNA-1273 booster
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1st Booster Dose | Change in Anti-Spike Antibody Titer Based on Type of Booster Administered | BNT162b2 | 5534 AU/mL |
| 1st Booster Dose | Change in Anti-Spike Antibody Titer Based on Type of Booster Administered | mRNA-1273 | 31451 AU/mL |
Post Hoc
Change in Anti-Spike Antibody Titer by Age
To investigate the association of age, median change in anti-S antibody titers were determined for the cohort of patients \<65 years old as opposed to the cohort of patients \>=65 years old.
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 106 total patients analyzed. Breakdowns by age categories described with corresponding median antibody titer results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1st Booster Dose | Change in Anti-Spike Antibody Titer by Age | <65 years old | 27451 AU/mL |
| 1st Booster Dose | Change in Anti-Spike Antibody Titer by Age | >=65 years old | 6152 AU/mL |
Post Hoc
Change in Anti-Spike Antibody Titer by Prior SARS-CoV-2 (COVID-19) Infection Status
Median change in anti-S antibody titer was determined based on previous SARS-CoV-2 (COVID-19) infection status
Time frame: Baseline to 4 weeks after administration of 1st booster dose
Population: 9 patients had prior COVID-19 infection, 96 patients did not have prior COVID-19 infection. Prior COVID-19 infection status was unknown for 1 patient.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1st Booster Dose | Change in Anti-Spike Antibody Titer by Prior SARS-CoV-2 (COVID-19) Infection Status | Previous COVID-19 infection | 19350 AU/mL |
| 1st Booster Dose | Change in Anti-Spike Antibody Titer by Prior SARS-CoV-2 (COVID-19) Infection Status | No Previous COVID-19 infection | 6706 AU/mL |
Post Hoc
Neutralization Against Wildtype (WT) SARS-CoV-2 Variant
Neutralization activity against the WT variant was assessed in the seronegative cohort using a neutralization activity assay. The percentage of patients with positive and negative results are reported.
Time frame: 4 weeks after administration of 1st booster dose
Population: 35 patients were found be seronegative after the 1st booster dose
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1st Booster Dose | Neutralization Against Wildtype (WT) SARS-CoV-2 Variant | Positive | 16 Participants |
| 1st Booster Dose | Neutralization Against Wildtype (WT) SARS-CoV-2 Variant | Negative | 19 Participants |
Post Hoc
Neutralization in Seronegative Cohort Against Omicron BA.1 Variant
Neutralization activity against the BA.1.1529 (Omicron BA.1) variant was assessed in the seronegative cohort using a neutralization activity assay. The percentage of patients with positive and negative results are reported.
Time frame: 4 weeks after administration of 1st booster dose
Population: 35 patients were found be seronegative after the 1st booster dose
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1st Booster Dose | Neutralization in Seronegative Cohort Against Omicron BA.1 Variant | Positive | 6 Participants |
| 1st Booster Dose | Neutralization in Seronegative Cohort Against Omicron BA.1 Variant | Negative | 29 Participants |
Post Hoc
Percentage of Patients Who Seroreverted
The percentage of patients who seroreverted (i.e., no longer had detectable serum antibody) was determined
Time frame: ~4-6 months after administration of 1st booster dose
Population: 47 patients completed their 4-6 month follow-up visit following 1st booster dose. All 47 were seropositive at 4 weeks. 36 of these patients had hematologic malignancies and 11 of these patients had solid malignancies. Six patients had received anti-COVID monoclonal antibody therapy as per standard of care between the 4 week and 4-6 months' follow-up period. Nine patients had received a fourth dose of COVID-19 vaccine outside of the context of the study prior to the time of 4-6 months' follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Percentage of Patients Who Seroreverted | 0 Participants |
Post Hoc
Percentage of Patients With Breakthrough SARS-CoV-2 Infections
The percentage of patients with breakthrough SARS-CoV-2 infections was determined.
Time frame: ~4-6 months after administration of 1st booster dose
Population: 47 patients completed their 4-6 month follow-up visit following 1st booster dose. All 47 were seropositive at 4 weeks. 36 of these patients had hematologic malignancies and 11 of these patients had solid malignancies. Six patients had received anti-COVID monoclonal antibody therapy as per standard of care between the 4 week and 4-6 months' follow-up period. Nine patients had received a fourth dose of COVID-19 vaccine outside of the context of the study prior to the time of 4-6 months' follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1st Booster Dose | Percentage of Patients With Breakthrough SARS-CoV-2 Infections | 4 Participants |