A Study Evaluating the Safety and Pharmacokinetics of Atezolizumab Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03922477
• Collaborator: (none)
• Enrollment: 13
• Locations: 4
• Arm: 1
• Actual Duration (Months): 12.9
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This Phase Ib study is designed to evaluate the safety and pharmacokinetics of atezolizumab when given in combination with Hu5F9-G4 to patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Atezolizumab; Drug: Hu5F9-G4	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib, Open-Label Study Evaluating the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia
• Actual Study Start Date: Oct 8, 2019
• Actual Primary Completion Date: Nov 3, 2020
• Actual Study Completion Date: Nov 3, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Atezolizumab + Hu5F9-G4 An initial safety evaluation will be performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 is initially safe and tolerable in participants an additional cohort with R/R AML will be evaluated to further test the safety and anti-tumor activity. If dose-limiting toxicities (DLT) are observed in >=33% of participants in this initial cohort, a dose de-escalation cohort will be enrolled. If less than 33% of enrolled and dosed participants in any given cohort experience a DLT, an expansion cohort of 15 participants will be enrolled at the highest tolerated dose for this combination. If a dose de-escalation cohort is needed, an expansion cohort will be enrolled at the lower tolerated dose for this combination.

Drug: Atezolizumab; Atezolizumab will be administered to participants by IV infusion at a fixed dose starting on Day 22 of Cycle 1. In subsequent cycles (Cycles 2 and beyond), IV atezolizumab will be given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle.; Other Names: Tecentriq ; Drug: Hu5F9-G4; Two priming doses of 1 mg/kg of Hu5F9-G4 will be administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance will be given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle. Dosing for de-escalation, if needed: Hu5F9-G4 will be given as two priming doses of 1 mg/kg IV on Days 1 and 4, followed by loading doses of 10 mg/kg IV on Day 8 and 15 mg/kg on Day 11. Starting on Day 15, maintenance treatment with Hu5F9-G4 will be given by IV infusion at a dose of 15 mg/kg once a week (QW).

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events [Up to approximately 13 months after first participant enrolled]

   Percentage of participants with at least one adverse event.

2. Complete Remission (CR) [Up to approximately 3 months after first participant enrolled]

   The CR rate is assessed as the percentage of participants who achieve a CR, complete remission with incomplete platelet recovery (CRp), complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh) (as defined by the IWG 2003 and ELN 2010 criteria) after up to six cycles of combination therapy.

3. Duration of Response (DOR) [Up to approximately 3 months after first particpant enrolled]

   DOR is defined as the time from the initial response (CR, CRp, CRi, CRh, or partial remission [PR]) to the time of disease progression or death, whichever occurs first

Secondary Outcome Measures

1. Serum Concentrations of Atezolizumab [C1 D22 PTFI of Hu5F9-G4 and atezolizumab, and 30 minutes after atezolizumab infusion; C2 D8 PTFI; C2 D22 PTFI; C3 D22 PTFI; C4 D22 PTFI; C8 D22 PTFI; C12 D22 PTFI; C16 D22 PTFI; TDV (up to C16 D21);120 days after final dose of atezolizumab (UTA 37M)]

   C=cycle (cycle=28 days) ; D=day; PTFI=prior to first infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=month

2. Serum Concentrations of Hu5F9-G4 [C1D1 PTFI&1H AEOI; C1D8 PTFI,&1H AEOI; C1D11 PTFI,&1H AEOI; C1D22 1H AEOI; C2D1 PTFI,&1H AEOI; C2D8 PTFI; C3D1 PTFI,&1H AEOI; C5D1 PTFI; C7D1 PTFI, C9D1 PTFI; C11D1 PTFI; C13D1 PTFI; C15D1 PTFI; C17D1&D1 E 2C T PTFI(UTA 37M);TDV(up to C16D21)(UTA 37M)]

   C=cycle (cycle=28 days); D=Day; PTFI=prior to first infusion; H=hour; AEOI=after end of infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=months; E=every; T=thereafter

3. Objective Response Rate [Up to approximately 3 months after first participant enrolled]

   Objective response rate is defined as the percentage of participants with a partial remission (PR) or better (i.e., CR + CRp + CRi + CRh+ PR).

4. Event-Free Survival [Up to approximately 3 months after first participant enrolled]

   Event-free survival is defined as the time from study entry to the date of induction treatment failure or relapse from CR, CRp, CRh, CRi, or death from any cause.

5. Leukemia-Free Survival [Up to approximately 3 months after first participant enrolled]

   Leukemia-free survival is defined (only for participants achieving a CR, CRp, CRh, or CRi) as the time from the date of achievement of remission (CR, CRp, or CRi) until the date of relapse from CR, CRp, CRh, CRi, or death from any cause.

6. Overall Survival [Up to approximately 13 months after first participant enrolled]

   Overall survival is defined as time from study entry to the date of death from any cause.

7. Progression-Free Survival [Up to approximately 3 months after first participant enrolled]

   Progression-free survival (Investigator) is defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.

8. Rate of Transfusion Independence [Up to approximately 3 months after first participant enrolled]

   Rate of transfusion independence is defined as the percentage of participants who achieve transfusion independence (i.e., achieving any continuous 56-day window without requiring platelet or RBC transfusions) at any time during study treatment.

9. Duration of Transfusion Independence [Up to approximately 3 months after first participant enrolled]

   Duration of transfusion independence is defined as the number of consecutive days of transfusion independence, measured from 1 day after the last transfusion to disease progression or subsequent transfusion.

10. Incidence of Anti-Drug Antibodies (ADAs) Against Atezolizumab During the Study Relative to the Prevalence of ADAs at Baseline [Baseline up to approximately 37 months]

11. Incidence of ADAs Against Hu5F9-G4 During the Study Relative to the Prevalence of ADAs at Baseline [Baseline up to approximately 37 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Life expectancy of at least 12 weeks

• Eastern Cooperative Oncology Group Performance Status 0-2

• Documented and confirmed R/R AML per WHO classification, except acute promyelocytic leukemia, and lack of response to all therapies of known benefit

• Adequate end-organ function

• Negative HIV test at screening

• Negative hepatitis B surface antigen (HBsAg) test at screening

• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA <500 IU/mL at screening

• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening

• Willingness and ability to provide pretreatment bone marrow aspirate and biopsy and agreement to provide subsequent bone marrow aspirates and biopsies during study treatment

• For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs

• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm

• For women who are not postmenopausal or surgically sterile: requirement for a negative serum pregnancy test result within 14 days prior to initiation of study treatment

Exclusion Criteria:

• Previous allogeneic hematopoietic stem cell transplant within 6 months prior to enrollment, active graft versus host disease, or requiring transplant-related immunosuppression

• Prior solid organ transplant

• Evidence of active central nervous system (CNS) involvement by leukemia

• Pregnancy or lactation or intention to become pregnant during the study or within 5 months after the final dose of atezolizumab and/or Hu5F9-G4, whichever is longer

• History of idiopathic pulmonary fibrosis, organizing pneumonitis, drug-induced pneumonitis, or idiopathic pneumonitis

• History of autoimmune disease. Patients with a history of autoimmune-related hypothyroidism who are on a stable dose of thyroid replacement may be eligible for this study. Patients with controlled Type 1 diabetes mellitus who are on a stable insulin regimen may be eligible for this study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of the following conditions are met: (1) Rash must cover <10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition that require psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.

• Treatment with investigational therapy within 14 days prior to initiation of study drug

• Any approved AML-related therapy within 14 days prior to enrollment. Granulocyte colony-stimulating factor to treat neutropenic fever and/or infection is permitted. Hydroxyurea may be used throughout the trial to control peripheral blood blast counts in response to the first dose of study treatment and during the first 4 weeks of study treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
2	Yale	New Haven	Connecticut	United States	06511
3	Columbia University	New York	New York	United States	10032-3725
4	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 5, 2020

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03922477
• Other Study ID Numbers: GO40828
• First Posted: Apr 22, 2019
• Last Update Posted: Feb 21, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Atezolizumab; Magrolimab

Study Results

Participant Flow

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Period Title: Overall Study
STARTED	13
COMPLETED	0
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Overall Participants	13
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.9 (8.9)
Sex: Female, Male (Count of Participants)
Female	8 61.5%
Male	5 38.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%
Not Hispanic or Latino	12 92.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 7.7%
White	11 84.6%
More than one race	0 0%
Unknown or Not Reported	1 7.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events
Description	Percentage of participants with at least one adverse event.
Time Frame	Up to approximately 13 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

Safety population included all participants with any amount of either study drug, with participants grouped as a whole.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	11
Number [Percentage of participants]	100 769.2%

2. Primary Outcome

Title	Complete Remission (CR)
Description	The CR rate is assessed as the percentage of participants who achieve a CR, complete remission with incomplete platelet recovery (CRp), complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh) (as defined by the IWG 2003 and ELN 2010 criteria) after up to six cycles of combination therapy.
Time Frame	Up to approximately 3 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

The efficacy analysis population included all participants who received any amount of either study drug, with participants grouped as a whole.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	11
Number [Percentage of participants]	0 0%

3. Primary Outcome

Title	Duration of Response (DOR)
Description	DOR is defined as the time from the initial response (CR, CRp, CRi, CRh, or partial remission [PR]) to the time of disease progression or death, whichever occurs first
Time Frame	Up to approximately 3 months after first particpant enrolled

Outcome Measure Data

Analysis Population Description

The efficacy analysis population included all participants who received any amount of either study drug, with participants grouped as a whole. No participants were analyzed because no participants responded.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	0

4. Secondary Outcome

Title	Serum Concentrations of Atezolizumab
Description	C=cycle (cycle=28 days) ; D=day; PTFI=prior to first infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=month
Time Frame	C1 D22 PTFI of Hu5F9-G4 and atezolizumab, and 30 minutes after atezolizumab infusion; C2 D8 PTFI; C2 D22 PTFI; C3 D22 PTFI; C4 D22 PTFI; C8 D22 PTFI; C12 D22 PTFI; C16 D22 PTFI; TDV (up to C16 D21);120 days after final dose of atezolizumab (UTA 37M)

Outcome Measure Data

Analysis Population Description

Samples for PK analysis were collected, but due to the small number of participants which reduces the scientific merit of any analysis no PK assays were performed and samples were discarded, hence no PK data are available.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	0

5. Secondary Outcome

Title	Serum Concentrations of Hu5F9-G4
Description	C=cycle (cycle=28 days); D=Day; PTFI=prior to first infusion; H=hour; AEOI=after end of infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=months; E=every; T=thereafter
Time Frame	C1D1 PTFI&1H AEOI; C1D8 PTFI,&1H AEOI; C1D11 PTFI,&1H AEOI; C1D22 1H AEOI; C2D1 PTFI,&1H AEOI; C2D8 PTFI; C3D1 PTFI,&1H AEOI; C5D1 PTFI; C7D1 PTFI, C9D1 PTFI; C11D1 PTFI; C13D1 PTFI; C15D1 PTFI; C17D1&D1 E 2C T PTFI(UTA 37M);TDV(up to C16D21)(UTA 37M)

Outcome Measure Data

Analysis Population Description

Samples for PK analysis were collected, but due to the small number of participants which reduces the scientific merit of any analysis no PK assays were performed and samples were discarded, hence no PK data are available.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	0

6. Secondary Outcome

Title	Objective Response Rate
Description	Objective response rate is defined as the percentage of participants with a partial remission (PR) or better (i.e., CR + CRp + CRi + CRh+ PR).
Time Frame	Up to approximately 3 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

The efficacy analysis population included all participants who received any amount of either study drug, with participants grouped as a whole.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	11
Number [Percentage of participants]	0 0%

7. Secondary Outcome

Title	Event-Free Survival
Description	Event-free survival is defined as the time from study entry to the date of induction treatment failure or relapse from CR, CRp, CRh, CRi, or death from any cause.
Time Frame	Up to approximately 3 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

The efficacy analysis population included all participants who received any amount of either study drug, with participants grouped as a whole.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	11
Median (95% Confidence Interval) [Months]	1.7

8. Secondary Outcome

Title	Leukemia-Free Survival
Description	Leukemia-free survival is defined (only for participants achieving a CR, CRp, CRh, or CRi) as the time from the date of achievement of remission (CR, CRp, or CRi) until the date of relapse from CR, CRp, CRh, CRi, or death from any cause.
Time Frame	Up to approximately 3 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

No participants were analyzed because no participants received an objective response.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	0

9. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as time from study entry to the date of death from any cause.
Time Frame	Up to approximately 13 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

The efficacy analysis population included all participants who received any amount of either study drug, with participants grouped as a whole.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	11
Median (95% Confidence Interval) [Months]	4.1

10. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-free survival (Investigator) is defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.
Time Frame	Up to approximately 3 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

The efficacy analysis population included all participants who received any amount of either study drug, with participants grouped as a whole.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	11
Median (95% Confidence Interval) [Months]	2.8

11. Secondary Outcome

Title	Rate of Transfusion Independence
Description	Rate of transfusion independence is defined as the percentage of participants who achieve transfusion independence (i.e., achieving any continuous 56-day window without requiring platelet or RBC transfusions) at any time during study treatment.
Time Frame	Up to approximately 3 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

The efficacy analysis population included all participants who received any amount of either study drug, with participants grouped as a whole.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	11
Number [Percentage of participants]	0 0%

12. Secondary Outcome

Title	Duration of Transfusion Independence
Description	Duration of transfusion independence is defined as the number of consecutive days of transfusion independence, measured from 1 day after the last transfusion to disease progression or subsequent transfusion.
Time Frame	Up to approximately 3 months after first participant enrolled

Outcome Measure Data

Analysis Population Description

None of the participants achieved transfusion independence, hence duration of independence was not calculated.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	0

13. Secondary Outcome

Title	Incidence of Anti-Drug Antibodies (ADAs) Against Atezolizumab During the Study Relative to the Prevalence of ADAs at Baseline
Time Frame	Baseline up to approximately 37 months

Outcome Measure Data

Analysis Population Description

Samples for ADA analysis were collected, but due to the small number of participants which reduces the scientific merit of any analysis no ADA assays were performed and samples were discarded, hence no ADA data are available.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	0

14. Secondary Outcome

Title	Incidence of ADAs Against Hu5F9-G4 During the Study Relative to the Prevalence of ADAs at Baseline
Time Frame	Baseline up to approximately 37 months

Outcome Measure Data

Analysis Population Description

Samples for ADA analysis were collected, but due to the small number of participants which reduces the scientific merit of any analysis no ADA assays were performed and samples were discarded, hence no ADA data are available.

Arm/Group Title	Atezolizumab + Hu5F9-G4
Arm/Group Description	An initial safety evaluation was performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 was initially safe and tolerable in participants an additional cohort with R/R AML was to be evaluated to further test the safety and anti-tumor activity. Atezolizumab was administered to participants by IV infusion at a fixed dose of 840 mg starting on Day 22 of Cycle 1. In subsequent cycles, IV atezolizumab was given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle. Two priming doses of 1 mg/kg of Hu5F9-G4 were administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance was given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle.
Measure Participants	0

Adverse Events

Time Frame	From the first study drug to the data cutoff date: 3 November 2020 (approximately 13 months)
Adverse Event Reporting Description	Safety population included all participants with any amount of either study drug, with participants grouped as a whole.
Arm/Group Title	Safety_Cohort
Arm/Group Description	An initial safety evaluation was to be performed in participants with relapsed AML. A total of 19 participants were screened for enrollment; 8 failed screening. 13 were enrolled but only 11 received study treatment. All 11 patients enrolled in the safety cohort discontinued the study.
All Cause Mortality
	Safety_Cohort
	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)
Serious Adverse Events
	Safety_Cohort
	Affected / at Risk (%)	# Events
Total	10/11 (90.9%)
Blood and lymphatic system disorders
Anaemia	2/11 (18.2%)	3
Infections and infestations
Pneumonia	5/11 (45.5%)	9
Sepsis	1/11 (9.1%)	2
Skin infection	1/11 (9.1%)	2
Urinary tract infection	1/11 (9.1%)	1
Injury, poisoning and procedural complications
Fracture	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/11 (9.1%)	1
Nervous system disorders
Cerebellar haemorrhage	1/11 (9.1%)	1
Haemorrhage intracranial	1/11 (9.1%)	2
Headache	1/11 (9.1%)	1
Renal and urinary disorders
Haematuria	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/11 (9.1%)	1
Respiratory failure	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Safety_Cohort
	Affected / at Risk (%)	# Events
Total	10/11 (90.9%)
Blood and lymphatic system disorders
Anaemia	5/11 (45.5%)	11
Coagulopathy	1/11 (9.1%)	1
Febrile neutropenia	1/11 (9.1%)	1
Haemolysis	1/11 (9.1%)	1
Leukocytosis	2/11 (18.2%)	2
Cardiac disorders
Cardiac failure	1/11 (9.1%)	1
Pericardial effusion	2/11 (18.2%)	2
Sinus tachycardia	1/11 (9.1%)	1
Ear and labyrinth disorders
Hypoacusis	2/11 (18.2%)	2
Gastrointestinal disorders
Abdominal pain	1/11 (9.1%)	1
Anal incontinence	1/11 (9.1%)	1
Constipation	2/11 (18.2%)	3
Diarrhoea	4/11 (36.4%)	6
Dry mouth	1/11 (9.1%)	1
Dysphagia	1/11 (9.1%)	1
Gastrooesophageal reflux disease	1/11 (9.1%)	1
Gingival bleeding	1/11 (9.1%)	1
Nausea	4/11 (36.4%)	4
Stomatitis	2/11 (18.2%)	3
Vomiting	2/11 (18.2%)	2
General disorders
Chills	1/11 (9.1%)	1
Fatigue	4/11 (36.4%)	4
Localised oedema	1/11 (9.1%)	1
Oedema peripheral	4/11 (36.4%)	5
Pyrexia	3/11 (27.3%)	4
Hepatobiliary disorders
Hyperbilirubinaemia	1/11 (9.1%)	1
Infections and infestations
Escherichia urinary tract infection	1/11 (9.1%)	1
Urinary tract infection	1/11 (9.1%)	1
Injury, poisoning and procedural complications
Contusion	1/11 (9.1%)	1
Fall	2/11 (18.2%)	2
Febrile nonhaemolytic transfusion reaction	1/11 (9.1%)	1
Infusion related reaction	4/11 (36.4%)	4
Procedural pain	1/11 (9.1%)	1
Skin abrasion	1/11 (9.1%)	2
Investigations
Blood alkaline phosphatase increased	2/11 (18.2%)	2
Blood creatinine increased	2/11 (18.2%)	4
Human rhinovirus test positive	1/11 (9.1%)	1
Liver function test increased	1/11 (9.1%)	1
Transaminases increased	1/11 (9.1%)	1
Weight decreased	1/11 (9.1%)	1
White blood cell count decreased	1/11 (9.1%)	1
Metabolism and nutrition disorders
Decreased appetite	3/11 (27.3%)	3
Electrolyte imbalance	1/11 (9.1%)	1
Hypermagnesaemia	1/11 (9.1%)	1
Hypernatraemia	1/11 (9.1%)	1
Hyperphosphataemia	1/11 (9.1%)	2
Hypoalbuminaemia	1/11 (9.1%)	1
Hypocalcaemia	3/11 (27.3%)	3
Hypokalaemia	4/11 (36.4%)	6
Hypomagnesaemia	3/11 (27.3%)	3
Hyponatraemia	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Bone pain	1/11 (9.1%)	1
Musculoskeletal pain	1/11 (9.1%)	1
Musculoskeletal stiffness	1/11 (9.1%)	1
Myalgia	1/11 (9.1%)	1
Nervous system disorders
Aphasia	1/11 (9.1%)	1
Dizziness	1/11 (9.1%)	1
Dysgeusia	1/11 (9.1%)	1
Headache	2/11 (18.2%)	3
Lethargy	1/11 (9.1%)	1
Psychiatric disorders
Agitation	1/11 (9.1%)	1
Anxiety	2/11 (18.2%)	2
Confusional state	1/11 (9.1%)	1
Delirium	1/11 (9.1%)	1
Depression	2/11 (18.2%)	2
Insomnia	1/11 (9.1%)	1
Renal and urinary disorders
Acute kidney injury	1/11 (9.1%)	1
Dysuria	1/11 (9.1%)	1
Pollakiuria	2/11 (18.2%)	3
Respiratory, thoracic and mediastinal disorders
Cough	2/11 (18.2%)	2
Dyspnoea	2/11 (18.2%)	3
Epistaxis	2/11 (18.2%)	2
Nasal congestion	1/11 (9.1%)	1
Oropharyngeal pain	2/11 (18.2%)	2
Pleural effusion	3/11 (27.3%)	4
Productive cough	2/11 (18.2%)	2
Rhinorrhoea	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/11 (9.1%)	1
Hyperhidrosis	1/11 (9.1%)	1
Petechiae	3/11 (27.3%)	3
Pruritus	2/11 (18.2%)	2
Rash	1/11 (9.1%)	1
Rash maculo-papular	3/11 (27.3%)	3
Vascular disorders
Haematoma	1/11 (9.1%)	3
Hypertension	2/11 (18.2%)	3
Hypotension	2/11 (18.2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.