Relapsed or Refractory Classical Hodgkin Lymphoma
Conditions
Keywords
Pharmacokinetics, Classical Hodgkin Lymphoma (cHL), Dose Expansion, Dose escalation, r/r cHL, programmed cell death protein-1 (PD-1), Accelerated titration design (ATD), T cell immunoglobulin and mucin domain-containing protein-3 (TIM-3), Modified toxicity probability interval-2 (mTPI-2), Bispecific antibody, Immunotherapy
Brief summary
The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of sabestomig (AZD7789) in patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL).
Detailed description
This is a Phase I/II, open-label multi-center study will have sabestomig administered via intravenous infusion on Cycle 1 Day 1 to adult/young adult patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL). This study will have 2 parts: Phase 1 (Part A) Dose Escalation and Phase 2 (Part B) Dose Expansion. Patients will be treated with study intervention for a maximum of 35 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent, or if other reasons to discontinue treatment occur. The trial was intended to be Phase I/II trial (but the trial never moved forward to Phase 2). Hence, the study Phase was updated to Phase I.
Interventions
DRUGSabestomig (AZD7789)
Patients will receive sabestomig (PD-1/TIM-3 bispecific monoclonal antibody) via intravenous infusion.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 101 Years
Healthy volunteers
No
Inclusion criteria
* ≥ 16 years of age at the time of obtaining informed consent * Eastern Cooperative Oncology Group performance status of 0 or 1 at screening * At least one positron emission tomography (PET)-avid measurable lesion according to Modified Lugano Criteria after the last line of therapy. * Confirmed histological diagnosis of active relapse/refractory cHL * Failed at least 2 prior lines of systemic therapy. * No previous treatment with anti-TIM-3. * Adequate organ and bone marrow function * Non-pregnant women and willingness of female patients to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception * Minimum body weight ≥ 40 kg for all participants.
Exclusion criteria
* Unresolved toxicities of ≥ Grade 2 from prior therapy * Any prior ≥ Grade 3 imAE while receiving prior checkpoint inhibitor immunotherapy * Patients with central nervous system (CNS) involvement or leptomeningeal disease. * History of allogeneic stem cell transplant or organ transplantation. * Any venous or arterial thromboembolic event within ≤ 6 months prior to the first dose of study intervention. * Active infection including Tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis A, chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19 infection * History of arrhythmia which is requires treatment, symptomatic or uncontrol led atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia * Uncontrolled intercurrent illness. * Active or prior documented pathologically confirmed autoimmune or inflammatory disorders. * Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD * Other invasive malignancy within 2 years prior to screening * Congenital long QT syndrome or history of QT prolongation associated with other medications that cannot be changed or discontinued based on a cardiologist assessment * Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention * Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B (Dose Expansion): Number of Participants With AEs | Up to approximately 2 years 90 days | The safety and tolerability of sabestomig in participants with r/r cHL was planned to be assessed. |
| Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | From start of treatment [Cycle 1 Day 1 (C1D1) (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months) | The safety and tolerability of sabestomig in participants with r/r cHL were assessed. |
| Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | From first dose (C1D1) until 28 days for each participant [within 28 days DLT period] | DLT was defined as any ≥Grade 3 AE as per NCI CTCAE version 5 unless unequivocally due to underlying malignancy or an extraneous cause. The following conditions were considered as DLTs: * Any death not clearly due to the underlying disease or extraneous causes * Grade 4 imAE or anemia * Any ≥Grade 3 non-infectious pneumonitis or colitis of any duration * Specific liver transaminase elevation as per protocol * Any Grade 3 imAE, including rash, pruritus, or diarrhea, that does not downgrade to Grade 2 or less within 7 days * Grade 3 nausea, vomiting, or diarrhea that does not resolve to Grade 2 or less within 3 days of getting maximal supportive care * ≥Grade 3 neutropenia, without fever or systemic infection, that does not improve by at least one grade within 7 days * Grade 4 thrombocytopenia for more than 7 days or ≥Grade 3 thrombocytopenia along with Grade ≥2 bleeding * Grade 4 Cytokine Release Syndrome (CRS) of any duration or Grade 3 CRS not improving to Grade ≤2 within 72 hours |
| Part B (Dose Expansion): Cohort B1: Objective Response Rate (ORR) | Up to approximately 2 years 90 days | The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. ORR was defined as the percentage of participants with an objective response \[Best Overall Response of a complete response (CR) or partial response (PR)\] as per modified Lugano criteria (Lugano 2014), with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was planned to be assessed according to Blinded Independent Central Review using modified Lugano criteria (Lugano 2014). |
| Part B (Dose Expansion): Cohort B2: Complete Response Rate (CRR) | Up to approximately 2 years 90 days | The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. The CRR was defined as the percentage of participants with a CR as per modified Lugano criteria (Lugano 2014), with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was planned to be assessed according to Blinded Independent Central Review using modified Lugano criteria (Lugano 2014). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A (Dose Escalation): Progression-free Survival (PFS) | From start of treatment [C1D1 (each cycle was 28 days)] until date of first documented disease progression or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months) | The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. PFS was defined as the time from first dose until the earlier of the date of first documented disease progression, as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, or death (by any cause in the absence of disease progression or subsequent anticancer treatment). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014). |
| Part A (Dose Escalation): Overall Survival (OS) | From start of treatment [C1D1 (each cycle was 28 days)] until date of death due to any cause or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months) | The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The OS was defined as the time from the start of treatment until death due to any cause regardless of whether participant withdraws from treatment or receives another anti-lymphoma therapy. |
| Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | On C1D1, C2D1, and until end of study [up to 2 years 5 months (each cycle was 28 days)] | The presence of ADA for sabestomig in treated participants with r/r cHL was assessed. |
| Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | From C1D1 [before start of infusion (SOI) and at end of infusion (EOI)] to end of study [up to 2 years 5 months (each cycle was 28 days)] | The Cmax of sabestomig in participants with r/r cHL was assessed. |
| Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC) | From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)] | The AUC of sabestomig in participants with r/r cHL was assessed. |
| Part A (Dose Escalation): Clearance (CL) | From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)] | The CL of sabestomig in participants with r/r cHL was assessed. |
| Part A (Dose Escalation): Terminal Elimination Half-life (t½λz) | From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)] | The t½λz of sabestomig in participants with r/r cHL was assessed. |
| Part B (Dose Expansion): Duration of Response (DoR) | Up to approximately 2 years 90 days | The DoR of sabestomig in participants with r/r cHL was planned to be assessed. |
| Part B (Dose Expansion): Duration of Complete Response (DoCR) | Up to approximately 2 years 90 days | The DoCR of sabestomig in participants with r/r cHL was planned to be assessed. |
| Part B (Dose Expansion): Overall Survival (OS) | Up to approximately 2 years 90 days | The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. |
| Part B (Dose Expansion): Number of Participants With Positive ADA Against Sabestomig in Serum | Up to approximately 2 years 90 days | The presence of ADA for sabestomig in treated participants with r/r cHL was planned to be assessed. |
| Part B (Dose Expansion): Maximum Observed Concentration (Cmax) | Up to approximately 2 years 90 days | The Cmax of sabestomig in participants with r/r cHL was planned to be assessed. |
| Part B (Dose Expansion): Area Under the Concentration-time Curve (AUC) | Up to approximately 2 years 90 days | The AUC of sabestomig in participants with r/r cHL was planned to be assessed. |
| Part B (Dose Expansion): Terminal Elimination Half-life (t½λz) | Up to approximately 2 years 90 days | The t½λz of sabestomig in participants with r/r cHL was planned to be assessed. |
| Part B (Dose Expansion): Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Up to approximately 2 years 90 days | Proportion of participants reporting different levels of presence/magnitude/interference (as applicable) of diarrhea, rash, and fatigue over time based on PRO-CTCAE was planned to be evaluated. PRO-CTCAE was a PRO measurement system developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE Item Library included 124 items representing 78 symptomatic toxicities drawn from the CTCAE. PRO-CTCAE items were planned to evaluate the symptom attributes of frequency, severity, interference, amount, presence/absence. Each symptomatic AE was planned to be assessed by 1 to 3 attributes. Conditional branching logic was planned to be used with electronic data capture, thereby reducing respondent burden. The recall period was planned as the past 7 days and PRO-CTCAE responses were planned to score from 0 to 4 (or 0/1 for absent/present). |
| Part B (Dose Expansion): Pediatric Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (Peds-PRO-CTCAE) | Up to approximately 2 years 90 days | Proportion of participants reporting different levels of presence/magnitude/interference (as applicable) of diarrhea, rash, and fatigue over time based on peds-PRO-CTCAE was planned to be evaluated. The pediatric module included 130 items representing 62 symptomatic toxicities and permitted self-reporting by children and adolescents aged 7 to 17 years. In this study, 17 symptomatic toxicities were planned for selection. Thus, the total number of questions that participants would have answered ranged from 17 (assuming that no branching questions were triggered, ie, the participant answered '0' to the initial question for each symptom) to 42 items (assuming that all possible branching questions were triggered for every symptom posed to the participant). |
| Part B (Dose Expansion): Patient Global Impression of Treatment Tolerability (PGI-TT) | Up to approximately 2 years 90 days | Proportion of participants reporting different levels of overall side-effect bother over time based on the PGI-TT was planned to be evaluated. For adult participants only, the PGI-TT item was included to assess how a participant perceived the overall burden of treatment-related side effects of cancer treatment over the past 7 days. Participants were planned to be asked to choose the response that best described the level of burden by the side effect of their cancer treatment over the past week. The planned response options were:not at all, a little bit, somewhat, quite a bit, and very much. |
| Part B (Dose Expansion): European Organization for Research and Treatment of Cancer (EORTC) Item List (IL)XX QL2 [2-item Global Health-related Quality of Life (HRQoL)] | Up to approximately 2 years 90 days | Proportion of participants reporting different levels of quality of life/health over time based on the European Organization for Research and Treatment of Cancer Item List (EORTC) ILXX QL2 items was planned to be evaluated. EORTC QLQ-C30 was a 30-item self-administered questionnaire designed for all cancer types. Questions were grouped into 5 multi-item functional scales (physical, role, emotional, cognitive, and social), 3 multi-item symptom scales (fatigue, pain, and nausea/vomiting), 2-item global HRQoL (QL2) scale, 5 single items assessing additional symptoms commonly reported by participants with cancer (dyspnea, loss of appetite, insomnia, constipation, and diarrhea), and 1 item on the financial impact of the disease. Participants were planned to answer QLQ-C30 questions in reference to how they had been over the past week. Final scores were planned to transform to range from 0 to 100, where higher scores indicated better functioning, better HRQoL, or greater level of symptoms. |
| Part B (Dose Expansion): Progression-free Survival (PFS) | Up to approximately 2 years 90 days | The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. |
| Part A (Dose Escalation): Complete Response Rate (CRR) | From start of treatment [C1D1 (each cycle was 28 days)] until first documented disease progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months) | The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The CRR was defined as the percentage of participants with a CR as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014). |
| Part A (Dose Escalation): Objective Response Rate (ORR) | From start of treatment [C1D1 (each cycle was 28 days)] until progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months) | The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The ORR was defined as the percentage of participants with an objective response (Best Overall Response of CR or PR) as per modified Lugano criteria (Lugano 2014), as assessed by the Investigator, with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014). |
| Part A (Dose Escalation): Duration of Response (DoR) | From first documented response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months) | The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The DoR was defined as the time from the date of first documented objective response (CR or PR), as assessed by Investigator, using the modified Lugano criteria (Lugano 2014), until the date of first documented disease progression or death (by any cause in the absence of disease progression). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014). |
| Part A (Dose Escalation): Duration of Complete Response (DoCR) | From first documented complete response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months) | The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The DoCR was defined as the time from first documented CR, as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, until the date of first documented relapse/progression or death due to any cause (in the absence of disease progression). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | From start of treatment [C1D1 (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months) | The safety and tolerability of sabestomig in participants with r/r cHL were assessed. An AESI was an AE of scientific and medical interest specific to understanding of a study intervention and may have required close monitoring and rapid communication to AstraZeneca by the Investigator. The AESIs for sabestomig include events with a potential inflammatory or immune-mediated mechanism and which may require more frequent monitoring and/or interventions such as steroids, immunosuppressants and/or hormone replacement therapy. |
Countries
Canada, Denmark, France, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled in this study from 18 March 2022 (First subject in) and the analyses presented in this results form are based on a final data cut-off (DCO) of 30 August 2024.
Pre-assignment details
Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. Part B was not initiated, therefore, no participant was enrolled and analyzed for this part of the study.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A1 Participants with r/r cHL previously treated with anti-PD-1/PD-L1 based therapy received 2mg of sabestomig. | 1 |
| Cohort A2 Participants with r/r cHL previously treated with anti-PD-1/PD-L1 based therapy received 7mg of sabestomig. | 1 |
| Cohort A3 Participants with r/r cHL previously treated with anti-PD-1/PD-L1 based therapy received 22.5mg of sabestomig. | 1 |
| Cohort A4 Participants with r/r cHL previously treated with anti-PD-1/PD-L1 based therapy received 75mg of sabestomig. | 1 |
| Cohort A5 Participants with r/r cHL previously treated with anti-PD-1/PD-L1 based therapy received 225mg of sabestomig. | 5 |
| Cohort A6 Participants with r/r cHL previously treated with anti-PD-1/PD-L1 based therapy received 750mg of sabestomig. | 12 |
| Cohort A7 Participants with r/r cHL previously treated with anti-PD-1/PD-L1 based therapy received 1500mg of sabestomig. | 12 |
| Cohort A8 Participants with r/r cHL previously treated with anti-PD-1/PD-L1 based therapy received 2000mg of sabestomig. | 12 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 |
| Overall Study | Ongoing as of DCO (30 Aug 2024) | 0 | 0 | 0 | 0 | 3 | 10 | 10 | 9 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Study terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort A1 | Cohort A2 | Cohort A3 | Cohort A4 | Cohort A5 | Cohort A6 | Cohort A7 | Cohort A8 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | NA Years | NA Years | NA Years | NA Years | 45.8 Years STANDARD_DEVIATION 17.6 | 44.4 Years STANDARD_DEVIATION 16 | 38.6 Years STANDARD_DEVIATION 14.5 | 52.1 Years STANDARD_DEVIATION 21.2 | 44.0 Years STANDARD_DEVIATION 17.4 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 12 Participants | 10 Participants | 10 Participants | 35 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Sex/Gender, Customized All | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Sex/Gender, Customized Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 6 Participants | 14 Participants |
| Sex/Gender, Customized Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 9 Participants | 10 Participants | 6 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 1 | 1 / 1 | 1 / 5 | 1 / 12 | 1 / 12 | 1 / 12 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 4 / 5 | 12 / 12 | 10 / 12 | 12 / 12 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 3 / 5 | 3 / 12 | 4 / 12 | 2 / 12 |
Outcome results
Primary
Part A (Dose Escalation): Number of Participants With Adverse Events (AEs)
The safety and tolerability of sabestomig in participants with r/r cHL were assessed.
Time frame: From start of treatment [Cycle 1 Day 1 (C1D1) (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months)
Population: Safety set included all participants who received any amount of study intervention.~CTCAE = Common Terminology Criteria for Adverse Events (version 5.0)~1. = As assessed by the investigator.~2. = AE of special interest derivations were programmed based on sponsor assessment of AE terms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also considered as an immune-mediated AE [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE | 1 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death) | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b], possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death), possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also an immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b], possibly related to Sabestomig [a] | 1 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] | 1 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE possibly related to Sabestomig [a] | 1 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE | 1 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also considered as an immune-mediated AE [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death) | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also an immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death), possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death) | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also considered as an immune-mediated AE [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death), possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also an immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b], possibly related to Sabestomig [a] | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE | 1 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] | 1 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE possibly related to Sabestomig [a] | 1 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE | 1 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also an immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death) | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death), possibly related to Sabestomig [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b], possibly related to Sabestomig [a] | 1 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also considered as an immune-mediated AE [a] | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death), possibly related to Sabestomig [a] | 2 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE | 4 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death) | 3 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also an immune-mediated AE, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig | 1 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also considered as an immune-mediated AE [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] | 2 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death | 1 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher | 1 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig | 1 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE possibly related to Sabestomig [a] | 3 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b], possibly related to Sabestomig [a] | 2 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] | 8 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE, possibly related to Sabestomig [a] | 3 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE | 12 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE possibly related to Sabestomig [a] | 10 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher | 4 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher, possibly related to Sabestomig [a] | 2 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death | 0 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death) | 2 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death), possibly related to Sabestomig [a] | 2 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig | 1 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 1 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay | 5 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay, possibly related to Sabestomig [a] | 2 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also considered as an immune-mediated AE [a] | 3 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b], possibly related to Sabestomig [a] | 6 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also an immune-mediated AE, possibly related to Sabestomig [a] | 3 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE [a] | 3 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE, possibly related to Sabestomig [a] | 2 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also an immune-mediated AE, possibly related to Sabestomig [a] | 2 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher, possibly related to Sabestomig [a] | 1 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE | 10 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher | 2 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also considered as an immune-mediated AE [a] | 2 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE [a] | 2 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b], possibly related to Sabestomig [a] | 4 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE possibly related to Sabestomig [a] | 8 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death), possibly related to Sabestomig [a] | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay | 4 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay, possibly related to Sabestomig [a] | 1 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death) | 2 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] | 7 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher, possibly related to Sabestomig [a] | 1 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 1 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of Sabestomig | 1 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also considered as an immune-mediated AE [a] | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE leading to discontinuation of Sabestomig | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death), possibly related to Sabestomig [a] | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] | 5 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b], possibly related to Sabestomig [a] | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any SAE (including events with outcome = death) | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of special interest [b] also an immune-mediated AE, possibly related to Sabestomig [a] | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE with outcome = death | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE of CTCAE grade 3 or higher | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE, possibly related to Sabestomig [a] | 3 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any immune-mediated AE [a] | 3 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE possibly related to Sabestomig [a] | 6 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE | 12 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay, possibly related to Sabestomig [a] | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events (AEs) | Any AE leading to cycle delay | 3 Participants |
Primary
Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs)
DLT was defined as any ≥Grade 3 AE as per NCI CTCAE version 5 unless unequivocally due to underlying malignancy or an extraneous cause. The following conditions were considered as DLTs: * Any death not clearly due to the underlying disease or extraneous causes * Grade 4 imAE or anemia * Any ≥Grade 3 non-infectious pneumonitis or colitis of any duration * Specific liver transaminase elevation as per protocol * Any Grade 3 imAE, including rash, pruritus, or diarrhea, that does not downgrade to Grade 2 or less within 7 days * Grade 3 nausea, vomiting, or diarrhea that does not resolve to Grade 2 or less within 3 days of getting maximal supportive care * ≥Grade 3 neutropenia, without fever or systemic infection, that does not improve by at least one grade within 7 days * Grade 4 thrombocytopenia for more than 7 days or ≥Grade 3 thrombocytopenia along with Grade ≥2 bleeding * Grade 4 Cytokine Release Syndrome (CRS) of any duration or Grade 3 CRS not improving to Grade ≤2 within 72 hours
Time frame: From first dose (C1D1) until 28 days for each participant [within 28 days DLT period]
Population: Safety set included all participants who received any amount of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | 1 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
Primary
Part B (Dose Expansion): Cohort B1: Objective Response Rate (ORR)
The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. ORR was defined as the percentage of participants with an objective response \[Best Overall Response of a complete response (CR) or partial response (PR)\] as per modified Lugano criteria (Lugano 2014), with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was planned to be assessed according to Blinded Independent Central Review using modified Lugano criteria (Lugano 2014).
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Primary
Part B (Dose Expansion): Cohort B2: Complete Response Rate (CRR)
The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. The CRR was defined as the percentage of participants with a CR as per modified Lugano criteria (Lugano 2014), with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was planned to be assessed according to Blinded Independent Central Review using modified Lugano criteria (Lugano 2014).
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Primary
Part B (Dose Expansion): Number of Participants With AEs
The safety and tolerability of sabestomig in participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC)
The AUC of sabestomig in participants with r/r cHL was assessed.
Time frame: From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
Population: PK set included all participants who received at least 1 dose of study intervention with at least 1 reportable concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A2 | Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC) | NA Day*ug/mL |
| Cohort A3 | Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC) | NA Day*ug/mL |
| Cohort A4 | Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC) | NA Day*ug/mL |
| Cohort A5 | Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC) | 273.00 Day*ug/mL |
| Cohort A6 | Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC) | 2256.00 Day*ug/mL |
| Cohort A7 | Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC) | 4687.00 Day*ug/mL |
| Cohort A8 | Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC) | 6883.00 Day*ug/mL |
Secondary
Part A (Dose Escalation): Clearance (CL)
The CL of sabestomig in participants with r/r cHL was assessed.
Time frame: From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
Population: PK set included all participants who received at least 1 dose of study intervention with at least 1 reportable concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A2 | Part A (Dose Escalation): Clearance (CL) | NA Liter (L)/Day |
| Cohort A3 | Part A (Dose Escalation): Clearance (CL) | NA Liter (L)/Day |
| Cohort A4 | Part A (Dose Escalation): Clearance (CL) | NA Liter (L)/Day |
| Cohort A5 | Part A (Dose Escalation): Clearance (CL) | 0.4925 Liter (L)/Day |
| Cohort A6 | Part A (Dose Escalation): Clearance (CL) | 0.2321 Liter (L)/Day |
| Cohort A7 | Part A (Dose Escalation): Clearance (CL) | 0.2211 Liter (L)/Day |
| Cohort A8 | Part A (Dose Escalation): Clearance (CL) | 0.2149 Liter (L)/Day |
Secondary
Part A (Dose Escalation): Complete Response Rate (CRR)
The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The CRR was defined as the percentage of participants with a CR as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).
Time frame: From start of treatment [C1D1 (each cycle was 28 days)] until first documented disease progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months)
Population: Response-evaluable set included all dosed participants who had measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Complete Response Rate (CRR) | NA Percentage of participants |
| Cohort A2 | Part A (Dose Escalation): Complete Response Rate (CRR) | NA Percentage of participants |
| Cohort A3 | Part A (Dose Escalation): Complete Response Rate (CRR) | NA Percentage of participants |
| Cohort A4 | Part A (Dose Escalation): Complete Response Rate (CRR) | NA Percentage of participants |
| Cohort A5 | Part A (Dose Escalation): Complete Response Rate (CRR) | 0 Percentage of participants |
| Cohort A6 | Part A (Dose Escalation): Complete Response Rate (CRR) | 33.3 Percentage of participants |
| Cohort A7 | Part A (Dose Escalation): Complete Response Rate (CRR) | 0 Percentage of participants |
| Cohort A8 | Part A (Dose Escalation): Complete Response Rate (CRR) | 0 Percentage of participants |
Secondary
Part A (Dose Escalation): Duration of Complete Response (DoCR)
The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The DoCR was defined as the time from first documented CR, as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, until the date of first documented relapse/progression or death due to any cause (in the absence of disease progression). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).
Time frame: From first documented complete response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
Population: Response-evaluable set included all dosed participants who had measurable disease at baseline.~Number of participants analyzed were number of participants with complete response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A6 | Part A (Dose Escalation): Duration of Complete Response (DoCR) | NA Months |
Secondary
Part A (Dose Escalation): Duration of Response (DoR)
The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The DoR was defined as the time from the date of first documented objective response (CR or PR), as assessed by Investigator, using the modified Lugano criteria (Lugano 2014), until the date of first documented disease progression or death (by any cause in the absence of disease progression). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).
Time frame: From first documented response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
Population: Response-evaluable set included all dosed participants who had measurable disease at baseline.~Number of participants analyzed were number of participants with objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Duration of Response (DoR) | NA Months |
| Cohort A2 | Part A (Dose Escalation): Duration of Response (DoR) | NA Months |
| Cohort A3 | Part A (Dose Escalation): Duration of Response (DoR) | NA Months |
| Cohort A4 | Part A (Dose Escalation): Duration of Response (DoR) | NA Months |
| Cohort A6 | Part A (Dose Escalation): Duration of Response (DoR) | NA Months |
| Cohort A7 | Part A (Dose Escalation): Duration of Response (DoR) | 7.7 Months |
| Cohort A8 | Part A (Dose Escalation): Duration of Response (DoR) | 6.3 Months |
Secondary
Part A (Dose Escalation): Maximum Observed Concentration (Cmax)
The Cmax of sabestomig in participants with r/r cHL was assessed.
Time frame: From C1D1 [before start of infusion (SOI) and at end of infusion (EOI)] to end of study [up to 2 years 5 months (each cycle was 28 days)]
Population: Pharmacokinetic (PK) set included all participants who received at least 1 dose of study intervention with at least 1 reportable concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | NA microgram (ug)/milliliter (mL) |
| Cohort A2 | Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | NA microgram (ug)/milliliter (mL) |
| Cohort A3 | Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | NA microgram (ug)/milliliter (mL) |
| Cohort A4 | Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | NA microgram (ug)/milliliter (mL) |
| Cohort A5 | Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | 52.49 microgram (ug)/milliliter (mL) |
| Cohort A6 | Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | 256.00 microgram (ug)/milliliter (mL) |
| Cohort A7 | Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | 516.00 microgram (ug)/milliliter (mL) |
| Cohort A8 | Part A (Dose Escalation): Maximum Observed Concentration (Cmax) | 695.10 microgram (ug)/milliliter (mL) |
Secondary
Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum
The presence of ADA for sabestomig in treated participants with r/r cHL was assessed.
Time frame: On C1D1, C2D1, and until end of study [up to 2 years 5 months (each cycle was 28 days)]
Population: Immunogenicity analysis set included all participants who received at least 1 dose of study intervention with at least 1 reportable immunogenicity measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA transient positive | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-boosted ADA | 1 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA incidence | 1 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and at least one post-baseline | 0 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA persistently positive | 1 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA prevalence | 1 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-induced ADA positive | 1 Participants |
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and not positive at post-baseline | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and not positive at post-baseline | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA prevalence | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-boosted ADA | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-induced ADA positive | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA persistently positive | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and at least one post-baseline | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA incidence | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA transient positive | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA persistently positive | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA incidence | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA transient positive | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and not positive at post-baseline | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-induced ADA positive | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA prevalence | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and at least one post-baseline | 0 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-boosted ADA | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA incidence | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA persistently positive | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-induced ADA positive | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-boosted ADA | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA prevalence | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and at least one post-baseline | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and not positive at post-baseline | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA transient positive | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and at least one post-baseline | 0 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA persistently positive | 2 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-boosted ADA | 3 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA incidence | 3 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA transient positive | 1 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA prevalence | 3 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-induced ADA positive | 3 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and not positive at post-baseline | 0 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA prevalence | 4 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA persistently positive | 2 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-induced ADA positive | 4 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and at least one post-baseline | 0 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and not positive at post-baseline | 0 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-boosted ADA | 3 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA incidence | 4 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA transient positive | 2 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA incidence | 4 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-induced ADA positive | 3 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and at least one post-baseline | 1 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and not positive at post-baseline | 0 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA transient positive | 2 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA persistently positive | 1 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA prevalence | 4 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-boosted ADA | 4 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA persistently positive | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA prevalence | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-induced ADA positive | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | Treatment-boosted ADA | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA incidence | 2 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and at least one post-baseline | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA positive at baseline and not positive at post-baseline | 0 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum | ADA transient positive | 0 Participants |
Secondary
Part A (Dose Escalation): Objective Response Rate (ORR)
The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The ORR was defined as the percentage of participants with an objective response (Best Overall Response of CR or PR) as per modified Lugano criteria (Lugano 2014), as assessed by the Investigator, with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).
Time frame: From start of treatment [C1D1 (each cycle was 28 days)] until progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months)
Population: Response-evaluable set included all dosed participants who had measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Objective Response Rate (ORR) | NA Percentage of participants |
| Cohort A2 | Part A (Dose Escalation): Objective Response Rate (ORR) | NA Percentage of participants |
| Cohort A3 | Part A (Dose Escalation): Objective Response Rate (ORR) | NA Percentage of participants |
| Cohort A4 | Part A (Dose Escalation): Objective Response Rate (ORR) | NA Percentage of participants |
| Cohort A5 | Part A (Dose Escalation): Objective Response Rate (ORR) | 0.0 Percentage of participants |
| Cohort A6 | Part A (Dose Escalation): Objective Response Rate (ORR) | 50.0 Percentage of participants |
| Cohort A7 | Part A (Dose Escalation): Objective Response Rate (ORR) | 25.0 Percentage of participants |
| Cohort A8 | Part A (Dose Escalation): Objective Response Rate (ORR) | 16.7 Percentage of participants |
Secondary
Part A (Dose Escalation): Overall Survival (OS)
The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. The OS was defined as the time from the start of treatment until death due to any cause regardless of whether participant withdraws from treatment or receives another anti-lymphoma therapy.
Time frame: From start of treatment [C1D1 (each cycle was 28 days)] until date of death due to any cause or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
Population: Full analysis set included all participants who received any amount of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Overall Survival (OS) | NA Months |
| Cohort A2 | Part A (Dose Escalation): Overall Survival (OS) | NA Months |
| Cohort A3 | Part A (Dose Escalation): Overall Survival (OS) | NA Months |
| Cohort A4 | Part A (Dose Escalation): Overall Survival (OS) | NA Months |
| Cohort A5 | Part A (Dose Escalation): Overall Survival (OS) | NA Months |
| Cohort A6 | Part A (Dose Escalation): Overall Survival (OS) | NA Months |
| Cohort A7 | Part A (Dose Escalation): Overall Survival (OS) | NA Months |
| Cohort A8 | Part A (Dose Escalation): Overall Survival (OS) | NA Months |
Secondary
Part A (Dose Escalation): Progression-free Survival (PFS)
The anti-tumor activity of sabestomig in participants with r/r cHL was assessed. PFS was defined as the time from first dose until the earlier of the date of first documented disease progression, as per modified Lugano criteria (Lugano 2014) as assessed by the Investigator, or death (by any cause in the absence of disease progression or subsequent anticancer treatment). Disease response was assessed according to Investigator assessment using modified Lugano criteria (Lugano 2014).
Time frame: From start of treatment [C1D1 (each cycle was 28 days)] until date of first documented disease progression or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months)
Population: Full analysis set included all participants who received any amount of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Progression-free Survival (PFS) | NA Months |
| Cohort A2 | Part A (Dose Escalation): Progression-free Survival (PFS) | NA Months |
| Cohort A3 | Part A (Dose Escalation): Progression-free Survival (PFS) | NA Months |
| Cohort A4 | Part A (Dose Escalation): Progression-free Survival (PFS) | NA Months |
| Cohort A5 | Part A (Dose Escalation): Progression-free Survival (PFS) | 1.9 Months |
| Cohort A6 | Part A (Dose Escalation): Progression-free Survival (PFS) | 4.8 Months |
| Cohort A7 | Part A (Dose Escalation): Progression-free Survival (PFS) | 5.7 Months |
| Cohort A8 | Part A (Dose Escalation): Progression-free Survival (PFS) | 2.1 Months |
Secondary
Part A (Dose Escalation): Terminal Elimination Half-life (t½λz)
The t½λz of sabestomig in participants with r/r cHL was assessed.
Time frame: From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)]
Population: PK set included all participants who received at least 1 dose of study intervention with at least 1 reportable concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A2 | Part A (Dose Escalation): Terminal Elimination Half-life (t½λz) | NA Day |
| Cohort A3 | Part A (Dose Escalation): Terminal Elimination Half-life (t½λz) | NA Day |
| Cohort A4 | Part A (Dose Escalation): Terminal Elimination Half-life (t½λz) | NA Day |
| Cohort A5 | Part A (Dose Escalation): Terminal Elimination Half-life (t½λz) | 9.136 Day |
| Cohort A6 | Part A (Dose Escalation): Terminal Elimination Half-life (t½λz) | 12.720 Day |
| Cohort A7 | Part A (Dose Escalation): Terminal Elimination Half-life (t½λz) | 16.440 Day |
| Cohort A8 | Part A (Dose Escalation): Terminal Elimination Half-life (t½λz) | 12.070 Day |
Secondary
Part B (Dose Expansion): Area Under the Concentration-time Curve (AUC)
The AUC of sabestomig in participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Duration of Complete Response (DoCR)
The DoCR of sabestomig in participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Duration of Response (DoR)
The DoR of sabestomig in participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): European Organization for Research and Treatment of Cancer (EORTC) Item List (IL)XX QL2 [2-item Global Health-related Quality of Life (HRQoL)]
Proportion of participants reporting different levels of quality of life/health over time based on the European Organization for Research and Treatment of Cancer Item List (EORTC) ILXX QL2 items was planned to be evaluated. EORTC QLQ-C30 was a 30-item self-administered questionnaire designed for all cancer types. Questions were grouped into 5 multi-item functional scales (physical, role, emotional, cognitive, and social), 3 multi-item symptom scales (fatigue, pain, and nausea/vomiting), 2-item global HRQoL (QL2) scale, 5 single items assessing additional symptoms commonly reported by participants with cancer (dyspnea, loss of appetite, insomnia, constipation, and diarrhea), and 1 item on the financial impact of the disease. Participants were planned to answer QLQ-C30 questions in reference to how they had been over the past week. Final scores were planned to transform to range from 0 to 100, where higher scores indicated better functioning, better HRQoL, or greater level of symptoms.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Maximum Observed Concentration (Cmax)
The Cmax of sabestomig in participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Number of Participants With Positive ADA Against Sabestomig in Serum
The presence of ADA for sabestomig in treated participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Overall Survival (OS)
The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Patient Global Impression of Treatment Tolerability (PGI-TT)
Proportion of participants reporting different levels of overall side-effect bother over time based on the PGI-TT was planned to be evaluated. For adult participants only, the PGI-TT item was included to assess how a participant perceived the overall burden of treatment-related side effects of cancer treatment over the past 7 days. Participants were planned to be asked to choose the response that best described the level of burden by the side effect of their cancer treatment over the past week. The planned response options were:not at all, a little bit, somewhat, quite a bit, and very much.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Proportion of participants reporting different levels of presence/magnitude/interference (as applicable) of diarrhea, rash, and fatigue over time based on PRO-CTCAE was planned to be evaluated. PRO-CTCAE was a PRO measurement system developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE Item Library included 124 items representing 78 symptomatic toxicities drawn from the CTCAE. PRO-CTCAE items were planned to evaluate the symptom attributes of frequency, severity, interference, amount, presence/absence. Each symptomatic AE was planned to be assessed by 1 to 3 attributes. Conditional branching logic was planned to be used with electronic data capture, thereby reducing respondent burden. The recall period was planned as the past 7 days and PRO-CTCAE responses were planned to score from 0 to 4 (or 0/1 for absent/present).
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Pediatric Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (Peds-PRO-CTCAE)
Proportion of participants reporting different levels of presence/magnitude/interference (as applicable) of diarrhea, rash, and fatigue over time based on peds-PRO-CTCAE was planned to be evaluated. The pediatric module included 130 items representing 62 symptomatic toxicities and permitted self-reporting by children and adolescents aged 7 to 17 years. In this study, 17 symptomatic toxicities were planned for selection. Thus, the total number of questions that participants would have answered ranged from 17 (assuming that no branching questions were triggered, ie, the participant answered '0' to the initial question for each symptom) to 42 items (assuming that all possible branching questions were triggered for every symptom posed to the participant).
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Progression-free Survival (PFS)
The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Secondary
Part B (Dose Expansion): Terminal Elimination Half-life (t½λz)
The t½λz of sabestomig in participants with r/r cHL was planned to be assessed.
Time frame: Up to approximately 2 years 90 days
Population: Part B was not initiated, therefore, no participant was enrolled and analyzed for this outcome measure.
Other Pre-specified
Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs)
The safety and tolerability of sabestomig in participants with r/r cHL were assessed. An AESI was an AE of scientific and medical interest specific to understanding of a study intervention and may have required close monitoring and rapid communication to AstraZeneca by the Investigator. The AESIs for sabestomig include events with a potential inflammatory or immune-mediated mechanism and which may require more frequent monitoring and/or interventions such as steroids, immunosuppressants and/or hormone replacement therapy.
Time frame: From start of treatment [C1D1 (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months)
Population: Safety set included all participants who received any amount of study intervention.~AE of special interest derivations were programmed based on sponsor assessment of AE terms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A1 | Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | 0 Participants |
| Cohort A2 | Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | 1 Participants |
| Cohort A3 | Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | 0 Participants |
| Cohort A4 | Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | 1 Participants |
| Cohort A5 | Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | 2 Participants |
| Cohort A6 | Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | 8 Participants |
| Cohort A7 | Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | 7 Participants |
| Cohort A8 | Part A (Dose Escalation): Number of Participants With Adverse Events of Special Interest (AESIs) | 5 Participants |