Leiomyosarcoma
Conditions
Keywords
Leiomyosarcoma, Pleomorphic sarcoma, Myxofibrosarcoma, Liposarcoma, Angiosarcoma, Epithelioid sarcoma
Brief summary
The purpose of this study is to learn about the safety and effects of the study medicine (called Ontorpacept or TTI-621) when given alone and when given in combination with doxorubicin for people with leiomyosarcoma. Leiomyosarcoma is a tumor of the smooth muscles. This study is seeking participants who have: * leiomyosarcoma that is advanced or has spread to other parts of the body (metastatic) * not received prior treatment with anthracyclines (a drug commonly used in patients with some kinds of cancer, including leiomyosarcoma) * not received more than one prior treatment for their leiomyosarcoma During the first 18 weeks of this study, participants will receive doxorubicin by IV infusion (given directly into a vein) at the study clinic every 3 weeks for a total of 6 doses. Participants will also receive Ontorpacept (TTI-621) by IV infusion at the study clinic on the same day as doxorubicin and again one week later for the first 18 weeks. After the first 18 weeks, participants will stop receiving doxorubicin but will continue receiving Ontorpacept (TTI-621) as IV infusion every 14 days at the study clinic. They will keep receiving Ontorpacept (TTI-621) until their cancer is no longer responding to treatment. We will examine the experiences of participants receiving Ontorpacept (TTI-621) in combination with doxorubicin in the first 18 weeks and then Ontorpacept (TTI-621) by itself after the doxorubicin is stopped. This will help us determine if the study medicine Ontorpacept (TTI-621) given with doxorubicin and then by itself is safe and effective. Participants will be involved in the study for approximately one year, depending on how their cancer responds to the study treatment. They will have study visits about 12 times in the first 18 weeks (when the study medicine Ontorpacept is given with doxorubicin) and then every two weeks after the doxorubicin is stopped and the study medicine Ontorpacept (TTI-621) is given by itself.
Detailed description
This trial will be conducted in 2 phases: Phase I (dose escalation of Ontorpacept in combination with fixed-dose doxorubicin) and Phase II (dose expansion of Ontorpacept in combination with fixed-dose doxorubicin). Phase I will enroll patients with soft-tissue sarcomas including leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma or epithelioid sarcoma to evaluate escalating doses of Ontorpacept (TTI-621) administered in combination with fixed-dose doxorubicin for up to six cycles followed by Ontorpacept (TTI-621) monotherapy. Phase II will enroll patients with high-grade leiomyosarcoma and will evaluate two dose levels of Ontorpacept (TTI-621) in combination with fixed-dose doxorubicin for up to six cycles followed by Ontorpacept (TTI-621) monotherapy. .
Interventions
DRUGOntorpacept (TTI-621)
Ontorpacept (TTI-621) will be administered by intravenous infusion.
DRUGDoxorubicin
75 mg/m\^2 by intravenous infusion in 21-day cycles for a maximum of six cycles.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Eastern Co-operative Oncology Group Performance Status Performance Status (ECOG-PS) 0 or 1. 2. Histologically-confirmed high-grade soft tissue sarcoma that is metastatic or locally advanced and not amenable to curative treatment with surgery or radiation. 1. In the Dose Escalation phase, indications will be limited to high-grade leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma and epithelioid sarcoma 2. In the Dose Expansion phase, indications will be limited to high-grade leiomyosarcoma. 3. Objective evidence of disease progression unless disease is newly-diagnosed. 4. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (expansion cohorts). 5. Adequate organ and hematologic function. 6. No more than 1 prior treatment regimen for advanced disease, which is limited to gemcitabine with docetaxel. 7. Anthracycline-naïve. 8. Patients who were treated with a prior chemotherapy regimen must have completed treatment at least three weeks before initiation of study treatment. 9. All adverse events from prior treatment must be NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v5 Grade ≤ 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline. 10. Radiotherapy, including palliative radiotherapy, completed at least two weeks prior to treatment; palliative radiation to non-target lesions while on study is allowed. Key
Exclusion criteria
1. History of acute coronary syndromes. 2. History of or current Class II, III, or IV heart failure. 3. History or evidence of known CNS (central nervous system) metastases or carcinomatous meningitis. 4. Significant bleeding disorders, vasculitis or a significant bleeding episode from the GI (gastrointestinal) tract. 5. History of severe hypersensitivity reactions to antibodies. 6. Systemic steroid therapy. 7. History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs. 8. Prior organ transplantation including allogenic or autologous stem cell transplantation 9. Prior treatment with anti-CD47 (Cluster of Differentiation 47) or anti-signal regulatory protein alpha (SIRPα) therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR): Phase I and Phase II | From the start of study treatment until disease progression (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II) | ORR: percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator's assessment per response evaluation criteria in solid tumours RECIST version (v)1.1. BOR: best response recorded from start of treatment until disease progression (PD). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than(\< )10 mm. PR: at least 30 percent (%) decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. PD: at least 20% increase in sum of longest diameter of target lesions, taking as reference of the smallest sum on study. |
| Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I | Baseline, 30 minutes post dose on Day 1 of Cycle 1 | Blood pressure included diastolic blood pressure (DBP) and systolic blood pressure (SBP). Mean change from baseline to 30 minutes post-dose on C1D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I | Baseline, 60 minutes post dose on Day 1 of Cycle 1 | Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C1D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I | Baseline, 30 minutes post dose on Day 8 of Cycle 1 | Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C1D8 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I | Baseline, 60 minutes post dose on Day 8 of Cycle 1 | Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C1D8 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I | Baseline, 30 minutes post dose on Day 1 of Cycle 2 | Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C2D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I | Baseline, 30 minutes post dose on Day 1 of Cycle 3 | Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C3D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I | Baseline, 60 minutes post dose on Day 1 of Cycle 3 | Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C3D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I | Baseline, Safety follow up (up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks) | Blood pressure included DBP and SBP. Mean change from baseline to safety follow up visit were reported in this outcome measure. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Body Weight at C3D1: Phase I | Baseline, Day 1 of Cycle 3 | Body weight was measured in kilograms (kg). Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Body Weight at Cycle 5 Day 1 (C5D1): Phase I | Baseline, Day 1 of Cycle 5 | Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Body Weight at Cycle 7 Day 1 (C7D1): Phase I | Baseline, Day 1 of Cycle 7 | Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Body Weight at Safety Follow up: Phase I | Baseline, Safety follow up (up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks) | Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Number of Participants With Overall Electrocardiogram (ECG) Abnormalities: Phase I | From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks) | Standard 12- lead ECGs, average of triplicate assessments were obtained in participant in supine position and within 10 minutes total time. ECG abnormalities included: PR interval (millisecond \[msec\]): value greater than or equal to (\>=) 220 and change from baseline \>=20; QRS interval (msec) value \>=120; uncorrected QT interval, QT correct by Bazzette's formula (QTcB) interval and QT correct by Frederica formula (QTcF) interval (msec): value greater than (\>) 450, value \> 480, value \> 500, change from baseline \> 30 and \> 60. Baseline was defined as the last assessment prior to the date or time of the first dose of study treatment. In this outcome measure number of participants with overall ECG abnormalities are reported. |
| Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks) | The following hematology laboratory parameters were assessed: hemoglobin, hematocrit, platelets, white blood cells (WBC), neutrophils, lymphocytes, eosinophils, basophils, monocytes, WBC with automated 5-part differential, Red blood cells (RBC), absolute reticulocytes, reticulocytes percentage (%), Mean corpuscular hemoglobin (MCH), Mean corpuscular volume (MCV) and Red cell distribution width (RDW). Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants who had hematology parameter abnormality Grade \<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported. |
| Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I | Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks) | The following chemistry parameters were assessed: glucose, sodium, potassium, calcium, chloride, phosphate, bicarbonate, blood urea nitrogen or urea, creatinine, total protein, albumin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, indirect bilirubin, uric acid, calcium, magnesium, lactate dehydrogenase (LDH). Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death related to adverse event. Baseline was defined as last assessment prior to date/time of first dose of study treatment. Number of participants who had chemistry parameter abnormality Grade\<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported. |
| Number of Participants With Dose Modifications: Phase I | During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 74.1 weeks for ontorpacept and 20.1 weeks for doxorubicin) | Dose modifications included dose reduction, dose omitted, infusion interruption and cycle delayed. |
| Number of Participants With Treatment Discontinuations: Phase I | During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 74.1 weeks for ontorpacept and 20.1 weeks for doxorubicin) | Number of participants with treatment discontinuations during the study treatment were reported in this outcome measure. |
| Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I | Baseline, 60 minutes post dose on Day 1 of Cycle 2 | Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C2D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I | From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks) | An adverse event (AE) was any untoward medical occurrence or worsening of a pre-existing medical condition following or during exposure to pharmaceutical product, whether or not considered causally related to product. A serious adverse event (SAE) was an adverse event occurred during any study at any dose of the investigational products that fulfils one or more of following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs were those events with onset date occurred during on-treatment period. AEs included SAEs and all Non-SAEs. On-treatment period was defined as time from first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer therapy). Participant with at least one TEAE and one serious TEAEs are reported in this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Blood Pressure: Phase II | Baseline, 30 and 60min post dose of C1D1,C1D8,C2D1,C3D1 and safety follow up 30 Days post last dose of study treatment/start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure of Phase II:88 weeks;maximum follow up:92 weeks) | Blood pressure included DBP and SBP. Mean change from baseline to safety follow up visit were reported in this outcome measure. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1). |
| Mean Change From Baseline in Body Weight: Phase II | Baseline, Day 1 of Cycle 3, 5, 7 and safety follow up (up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest [maximum treatment exposure for Phase II was 88 weeks; maximum follow up to 92 weeks]) | Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1) |
| Number of Participants With Overall ECG Abnormalities: Phase II | From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks) | Standard 12- lead ECGs, average of triplicate assessments was obtained in participant in supine position and within 10 minutes total time. ECG abnormalities included: PR interval (msec): \>= 220 and change from baseline \>=20; QRS interval (msec) value \>=120; uncorrected QT interval, QT correct by QTcB interval and QT correct by QTcF interval (msec): value \> 450, value \> 480, value \> 500, change from baseline \> 30 and \> 60. Baseline was defined as the last assessment prior to the date or time of the first dose of study treatment. In this outcome measure number of participants with overall ECG abnormalities are reported. |
| Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks) | The following hematology laboratory parameters were assessed: hemoglobin, hematocrit, platelets, WBC, neutrophils, lymphocytes, eosinophils, basophils, monocytes, WBC with automated 5-part differential, RBC, absolute reticulocytes, reticulocytes %, MCH, MCV and RDW. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants who had hematology parameter abnormality Grade \<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported. |
| Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks) | The following chemistry parameters were assessed: glucose, sodium, potassium, calcium, chloride, phosphate, bicarbonate, blood urea nitrogen or urea, creatinine, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin, indirect bilirubin, uric acid, calcium, magnesium and LDH. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death related to adverse event. Baseline was defined as last assessment prior to date/time of first dose of study treatment. Number of participants who had chemistry parameter abnormality Grade\<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported. |
| Number of Participants With Dose Modifications: Phase II | During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 88 weeks for ontorpacept and 25 weeks for doxorubicin) | Dose modifications included dose reduction, dose omitted, infusion interruption and cycle delayed. |
| Number of Participants With Treatment Discontinuations: Phase II | During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 88 weeks for ontorpacept and 25 weeks for doxorubicin) | Number of participants with treatment discontinuations during the study treatment were reported in this outcome measure. |
| Progression Free Survival (PFS): Phase I and Phase II | Time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II) | PFS was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause, whichever occurred first. PD was defined at least 20% increase in sum of longest diameter (LD) of target lesion, taking reference of smallest sum on study. Participants without PD or death or participants with an event after 2 or more missing/inadequate disease assessment or participants with an event after the start date of alternate anticancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy, whichever is earlier. Kaplan-Meier method was used for analysis. |
| Overall Survival (OS): Phase I and Phase II | From the first ontorpacept infusion (Day 1 of Cycle 1) to death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II) | OS was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to death of any cause. Participants last known to be alive were censored at their last known alive date. Kaplan-Meier method was used for analysis. |
| Disease Control Rate (DCR): Phase I and Phase II | From the first dose of study treatment until PD or death, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II) | DCR was defined as the percentage of participants who have achieved CR, PR, or SD lasting at least 4 weeks as per RECIST v1.1 CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: at least 30% decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum LD since treatment started. PD: at least 20% increase in sum of longest diameter of target lesions, taking as reference of the smallest sum on study. |
| Duration of Response (DOR): Phase I and Phase II | Time from date of first documented response (CR or PR) to date of documented progression or death of any cause after achieving response or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II) | DOR was defined as time from date of first documented response (CR or PR) to date of documented progression or death of any cause after achieving response. DOR was calculated for participants who achieved CR or PR. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: at least 30% decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. Participants without PD or death or participants with an event after 2 or more missing/inadequate disease assessment or participants with an event after the start date of alternate anticancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy, whichever is earlier. |
| Duration of Disease Control (DDC): Phase I and Phase II | Time from first ontorpacept infusion (Day 1 of Cycle 1) to date of documented progression/death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II) | DDC: participants who achieved BOR of SD, as time from first ontorpacept infusion (Day1 of Cycle1) to date of documented PD/death of any cause. Calculated for participants who achieved CR,PR/SD lasting at least 4weeks. CR:disappearance of all target lesion. Any pathological lymph nodes must have reduction in short axis to\<10 mm. PR:at least 30%decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum LD since treatment started. PD:at least 20% increase in sum of LD of target lesion, taking reference of smallest sum on study. Participants without PD/death/with an event after 2/more missing/inadequate disease assessment/with event after start date of alternate anticancer therapy were censored at last response assessment date/last assessment prior to start date of alternate anti-cancer therapy, whichever is earlier. |
| Time to Progression (TTP): Phase I and Phase II | Time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause or censoring, whichever is first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II) | TTP was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause, whichever is first; provided death was not considered as an event. PD: at least 20% increase in sum of longest diameter of target lesion, taking reference of smallest sum on study. Participants without PD or death or with an event after 2 or more missing or inadequate disease assessment or with event after start date of alternate anticancer therapy were censored at last response assessment date or last assessment prior to start date of alternate anti-cancer therapy, whichever is earlier. |
| Time to New Metastases: Phase I and Phase II | Time from the first ontorpacept infusion (Day 1 of Cycle 1) until the appearance of new lesion or death or censoring date, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II) | Time to new metastasis was defined as the time from the ontorpacept infusion (Day 1 of Cycle 1) to a new lesion appearance. Participants without new lesion or participants with new metastases after 2 or more missing/inadequate disease assessment or participants with new metastases after the start date of alternate anti-cancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy whichever was earlier. |
| Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II | From Baseline up to 30 Days post last dose of study treatment/start of new anti-cancer therapy whichever occurred first (maximum exposure upto 74.1 and 88 weeks; maximum follow up to approx. 78.1 and 92 weeks for Phase I and II respectively) | ECOG performance were classified as 5 grades: 0: fully active, able to carry on all pre-disease performance without restriction; 1: restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2: ambulatory and capable of all selfcare but unable to carry out any work activities, up and about more than 50% of waking hours; 3: capable of only limited selfcare, confined to bed or chair more than 50% of waking hours and 4: completely disabled, cannot carry on selfcare and totally confined to bed or chair. Higher score indicated lower health status. Worsening of ECOG was defined as a worsening from baseline (i.e., increase) in the ECOG assessment level and was recorded in two consecutive assessments. |
| Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II | From Baseline up to 30 Days post last dose of study treatment/start of new anti-cancer therapy whichever occurred first (maximum exposure upto 74.1 and 88 weeks; maximum follow up to approx. 78.1 and 92 weeks for Phase I and II respectively) | QOL was assessed with European organisation for research and treatment of cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) tool. The EORTC QLQ-C30 is self-administered, self-reported general cancer-specific questionnaire consisting of 30 items covered by one of 3 dimensions: global health status (2 items): functional scales(15 total items addressing either physical, emotional, cognitive/social functioning) and symptom scales(13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea/financial impact). Higher score indicated better overall QoL. Worsening of Global Health Status /QoL assessments was defined as at least a 10-point decrease from baseline in the standardized score (linear transformation) of Global Health Status/QoL. |
| Number of Participants With TEAEs and Serious TEAEs: Phase II | From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks) | An AE was any untoward medical occurrence or worsening of a pre-existing medical condition following or during exposure to pharmaceutical product, whether or not considered causally related to product. A SAE was an adverse event occurred during any study at any dose of the investigational products that fulfils one or more of following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs were those events with onset date occurred during on-treatment period. AEs included SAEs and all Non-SAEs. On-treatment period was defined as time from first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer therapy). Participant with at least one TEAE and one serious TEAEs are reported in this outcome measure. |
Countries
United States
Participant flow
Recruitment details
The study consisted of two phases: Phase I (dose escalation) and Phase II (dose expansion). Phase I enrolled participants with high-grade leiomyosarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, angiosarcoma and epithelioid sarcoma. Phase II enrolled participants with high-grade leiomyosarcoma. Participants were treated with ontorpacept (TTI-621) in combination with doxorubicin for the first 6 cycles and ontorpacept alone thereafter.
Pre-assignment details
A total of 76 participants were enrolled and treated in the study (Phase I: 9 participants and Phase II: 67 participants).
Participants by arm
| Arm | Count |
|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin Participants received ontorpacept, 0.2 mg/kg as IV infusion on Days 1 and 8 of each 21-day cycle up to Cycle 6. Doxorubicin 75 mg/m\^2 was administered as IV infusion on Day 1 of 21-day cycles for a maximum of 6 cycles. After Cycle 6, participants continued treatment with ontorpacept 0.2 mg/kg as IV infusion on Days 1 and 15 as monotherapy in 28-day cycles until documentation of disease progression or development of unacceptable toxicity and a long-term follow-up period for assessment of overall survival. | 3 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin Participants received ontorpacept, 0.7 mg/kg as IV infusion on Days 1 and 8 of each 21-day cycle up to Cycle 6. Doxorubicin 75 mg/m\^2 was administered as IV infusion on Day 1 of 21-day cycles for a maximum of 6 cycles. After Cycle 6, participants continued treatment with ontorpacept 0.7 mg/kg as IV infusion on Days 1 and 15 as monotherapy in 28-day cycles until documentation of disease progression or development of unacceptable toxicity and a long-term follow-up period for assessment of overall survival. | 3 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin Participants received ontorpacept, 2.0 mg/kg as IV infusion on Days 1 and 8 of each 21-day cycle up to Cycle 6. Doxorubicin 75 mg/m\^2 was administered as IV infusion on Day 1 of 21-day cycles for a maximum of 6 cycles. After Cycle 6, participants continued treatment with ontorpacept 2.0 mg/kg as IV infusion on Days 1 and 15 as monotherapy in 28-day cycles until documentation of disease progression or development of unacceptable toxicity and a long-term follow-up period for assessment of overall survival. | 3 |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) Participants received ontorpacept, 0.2 mg/kg as IV infusion on Days 1 and 8 of each 21-day cycle up to Cycle 6. Doxorubicin 75 mg/m\^2 was administered as IV infusion on Day 1 of 21-day cycles for a maximum of 6 cycles. After Cycle 6, participants continued treatment with ontorpacept 0.2 mg/kg as IV infusion on Days 1 and 15 as monotherapy in 28-day cycles until documentation of disease progression or development of unacceptable toxicity and a long-term follow-up period for assessment of overall survival. | 32 |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) Participants received ontorpacept, 1.0 mg/kg as IV infusion on Days 1 and 8 of each 21-day cycle up to Cycle 6. Doxorubicin 75 mg/m\^2 was administered as IV infusion on Day 1 of 21-day cycles for a maximum of 6 cycles. After Cycle 6, participants continued treatment with ontorpacept 1.0 mg/kg as IV infusion on Days 1 and 15 as monotherapy in 28-day cycles until documentation of disease progression or development of unacceptable toxicity and a long-term follow-up period for assessment of overall survival. | 13 |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) Participants received ontorpacept, 2.0 mg/kg as IV infusion on Days 1 and 8 of each 21-day cycle up to Cycle 6. Doxorubicin 75 mg/m\^2 was administered as IV infusion on Day 1 of 21-day cycles for a maximum of 6 cycles. After Cycle 6, participants continued treatment with ontorpacept 2.0 mg/kg as IV infusion on Days 1 and 15 as monotherapy in 28-day cycles until documentation of disease progression or development of unacceptable toxicity and a long-term follow-up period for assessment of overall survival. | 22 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Phase I | Death | 1 | 2 | 1 | 0 | 0 | 0 |
| Phase I | Study terminated by sponsor | 2 | 1 | 2 | 0 | 0 | 0 |
| Phase II | Death | 0 | 0 | 0 | 12 | 2 | 9 |
| Phase II | Other | 0 | 0 | 0 | 0 | 0 | 1 |
| Phase II | Study terminated by sponsor | 0 | 0 | 0 | 20 | 10 | 10 |
| Phase II | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Total | Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin |
|---|---|---|---|---|---|---|---|
| Age, Customized 40 - <65 years | 2 Participants | 49 Participants | 12 Participants | 7 Participants | 25 Participants | 2 Participants | 1 Participants |
| Age, Customized 65 - <75 years | 0 Participants | 18 Participants | 7 Participants | 5 Participants | 4 Participants | 1 Participants | 1 Participants |
| Age, Customized 75 - <85 years | 0 Participants | 4 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Customized Less than (<) 40 years | 1 Participants | 5 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 9 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 64 Participants | 19 Participants | 10 Participants | 29 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 64 Participants | 22 Participants | 10 Participants | 24 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 55 Participants | 16 Participants | 10 Participants | 23 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 21 Participants | 6 Participants | 3 Participants | 9 Participants | 0 Participants | 2 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 2 / 3 | 1 / 3 | 12 / 32 | 2 / 13 | 9 / 22 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 24 / 32 | 12 / 13 | 21 / 22 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 1 / 3 | 9 / 32 | 8 / 13 | 15 / 22 |
Outcome results
Primary
Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I
Blood pressure included diastolic blood pressure (DBP) and systolic blood pressure (SBP). Mean change from baseline to 30 minutes post-dose on C1D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 30 minutes post dose on Day 1 of Cycle 1
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I | DBP | -0.7 Millimeter of mercury (mmHg) | Standard Deviation 5.86 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I | SBP | 1.7 Millimeter of mercury (mmHg) | Standard Deviation 8.02 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I | DBP | -0.7 Millimeter of mercury (mmHg) | Standard Deviation 3.51 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I | SBP | 2.0 Millimeter of mercury (mmHg) | Standard Deviation 3.61 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I | DBP | 1.0 Millimeter of mercury (mmHg) | Standard Deviation 8.72 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 1 (C1D1): Phase I | SBP | -8.7 Millimeter of mercury (mmHg) | Standard Deviation 4.73 |
Primary
Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I
Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C1D8 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 30 minutes post dose on Day 8 of Cycle 1
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I | DBP | 1.3 Millimeter of mercury | Standard Deviation 10.02 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I | SBP | 7.0 Millimeter of mercury | Standard Deviation 11.36 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I | DBP | 2.7 Millimeter of mercury | Standard Deviation 5.03 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I | SBP | 5.0 Millimeter of mercury | Standard Deviation 6.93 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I | DBP | 0.3 Millimeter of mercury | Standard Deviation 2.89 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 1 Day 8 (C1D8): Phase I | SBP | -7.3 Millimeter of mercury | Standard Deviation 7.51 |
Primary
Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I
Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C2D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 30 minutes post dose on Day 1 of Cycle 2
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I | DBP | 3.0 Millimeter of mercury | Standard Deviation 3.46 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I | SBP | 4.0 Millimeter of mercury | Standard Deviation 5.29 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I | DBP | -2.0 Millimeter of mercury | Standard Deviation 6.24 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I | SBP | -5.7 Millimeter of mercury | Standard Deviation 6.51 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I | DBP | 6.5 Millimeter of mercury | Standard Deviation 3.54 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 2 Day 1 (C2D1): Phase I | SBP | 3.5 Millimeter of mercury | Standard Deviation 16.26 |
Primary
Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I
Blood pressure included DBP and SBP. Mean change from baseline to 30 minutes post-dose on C3D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 30 minutes post dose on Day 1 of Cycle 3
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I | DBP | -3.5 Millimeter of mercury | Standard Deviation 6.36 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I | SBP | -6.5 Millimeter of mercury | Standard Deviation 17.68 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I | DBP | -5.5 Millimeter of mercury | Standard Deviation 4.95 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I | SBP | -14.0 Millimeter of mercury | Standard Deviation 0 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I | DBP | 2.0 Millimeter of mercury | — |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 30 Minutes Post Dose on Cycle 3 Day 1 (C3D1): Phase I | SBP | -8.0 Millimeter of mercury | — |
Primary
Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I
Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C1D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 60 minutes post dose on Day 1 of Cycle 1
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I | DBP | 2.3 Millimeter of mercury | Standard Deviation 2.08 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I | SBP | 3.0 Millimeter of mercury | Standard Deviation 5 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I | DBP | 0.7 Millimeter of mercury | Standard Deviation 3.21 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I | SBP | -0.7 Millimeter of mercury | Standard Deviation 2.89 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I | DBP | 1.7 Millimeter of mercury | Standard Deviation 9.29 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D1: Phase I | SBP | -8.3 Millimeter of mercury | Standard Deviation 10.12 |
Primary
Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I
Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C1D8 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 60 minutes post dose on Day 8 of Cycle 1
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I | DBP | 0.3 Millimeter of mercury | Standard Deviation 9.81 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I | SBP | 3.3 Millimeter of mercury | Standard Deviation 9.07 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I | DBP | -4.0 Millimeter of mercury | Standard Deviation 7.94 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I | SBP | 2.3 Millimeter of mercury | Standard Deviation 9.29 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I | DBP | 0.7 Millimeter of mercury | Standard Deviation 6.51 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C1D8: Phase I | SBP | -1.0 Millimeter of mercury | Standard Deviation 11.53 |
Primary
Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I
Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C2D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 60 minutes post dose on Day 1 of Cycle 2
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I | DBP | 3.0 Millimeter of mercury | Standard Deviation 5.2 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I | SBP | 5.0 Millimeter of mercury | Standard Deviation 5.57 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I | DBP | -3.7 Millimeter of mercury | Standard Deviation 8.02 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I | SBP | -2.0 Millimeter of mercury | Standard Deviation 14.73 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I | DBP | 11.0 Millimeter of mercury | Standard Deviation 1.41 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C2D1: Phase I | SBP | 10.5 Millimeter of mercury | Standard Deviation 24.75 |
Primary
Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I
Blood pressure included DBP and SBP. Mean change from baseline to 60 minutes post-dose on C3D1 were reported in this outcome measure. Baseline was defined as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 60 minutes post dose on Day 1 of Cycle 3
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I | DBP | 0.5 Millimeter of mercury | Standard Deviation 6.36 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I | SBP | -1.0 Millimeter of mercury | Standard Deviation 7.07 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I | DBP | -2.0 Millimeter of mercury | Standard Deviation 2.83 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I | SBP | -12.0 Millimeter of mercury | Standard Deviation 4.24 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I | DBP | 6.0 Millimeter of mercury | — |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at 60 Minutes Post Dose on C3D1: Phase I | SBP | -11.0 Millimeter of mercury | — |
Primary
Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I
Blood pressure included DBP and SBP. Mean change from baseline to safety follow up visit were reported in this outcome measure. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, Safety follow up (up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I | DBP | 7.0 Millimeter of mercury | Standard Deviation 2.83 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I | SBP | 13.5 Millimeter of mercury | Standard Deviation 14.85 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I | DBP | -10.3 Millimeter of mercury | Standard Deviation 2.89 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I | SBP | -15.7 Millimeter of mercury | Standard Deviation 10.07 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I | DBP | 3.0 Millimeter of mercury | Standard Deviation 13.08 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure at Safety Follow up: Phase I | SBP | 8.7 Millimeter of mercury | Standard Deviation 12.66 |
Primary
Mean Change From Baseline in Body Weight at C3D1: Phase I
Body weight was measured in kilograms (kg). Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, Day 1 of Cycle 3
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at C3D1: Phase I | 0.68 Kilograms | Standard Deviation 0.962 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at C3D1: Phase I | -3.86 Kilograms | Standard Deviation 2.885 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at C3D1: Phase I | -1.71 Kilograms | Standard Deviation 0.148 |
Primary
Mean Change From Baseline in Body Weight at Cycle 5 Day 1 (C5D1): Phase I
Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, Day 1 of Cycle 5
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Cycle 5 Day 1 (C5D1): Phase I | -0.91 Kilograms | Standard Deviation 0 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Cycle 5 Day 1 (C5D1): Phase I | -2.50 Kilograms | Standard Deviation 5.452 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Cycle 5 Day 1 (C5D1): Phase I | -2.09 Kilograms | Standard Deviation 1.534 |
Primary
Mean Change From Baseline in Body Weight at Cycle 7 Day 1 (C7D1): Phase I
Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, Day 1 of Cycle 7
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Cycle 7 Day 1 (C7D1): Phase I | -0.91 Kilograms | Standard Deviation 0.636 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Cycle 7 Day 1 (C7D1): Phase I | -0.23 Kilograms | Standard Deviation 2.249 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Cycle 7 Day 1 (C7D1): Phase I | -1.26 Kilograms | Standard Deviation 0.785 |
Primary
Mean Change From Baseline in Body Weight at Safety Follow up: Phase I
Body weight was measured in kilograms. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, Safety follow up (up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Safety Follow up: Phase I | 1.13 kilograms | Standard Deviation 0.325 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Safety Follow up: Phase I | -3.48 kilograms | Standard Deviation 1.889 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight at Safety Follow up: Phase I | -1.56 kilograms | Standard Deviation 1.794 |
Primary
Number of Participants With Dose Modifications: Phase I
Dose modifications included dose reduction, dose omitted, infusion interruption and cycle delayed.
Time frame: During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 74.1 weeks for ontorpacept and 20.1 weeks for doxorubicin)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with infusion interruption-Ontorpacept | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose reduction- Ontorpacept | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with cycle delayed- Ontorpacept | 1 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with cycle delayed- Doxorubicin | 1 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose omitted- Ontorpacept | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose reduction- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with infusion interruption-Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose omitted- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose omitted- Ontorpacept | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose omitted- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose reduction- Ontorpacept | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with infusion interruption-Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with cycle delayed- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with infusion interruption-Ontorpacept | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with cycle delayed- Ontorpacept | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose reduction- Doxorubicin | 1 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with cycle delayed- Ontorpacept | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose reduction- Ontorpacept | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose omitted- Ontorpacept | 2 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with infusion interruption-Ontorpacept | 1 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with cycle delayed- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose reduction- Doxorubicin | 2 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with dose omitted- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase I | Participants with infusion interruption-Doxorubicin | 0 Participants |
Primary
Number of Participants With Overall Electrocardiogram (ECG) Abnormalities: Phase I
Standard 12- lead ECGs, average of triplicate assessments were obtained in participant in supine position and within 10 minutes total time. ECG abnormalities included: PR interval (millisecond \[msec\]): value greater than or equal to (\>=) 220 and change from baseline \>=20; QRS interval (msec) value \>=120; uncorrected QT interval, QT correct by Bazzette's formula (QTcB) interval and QT correct by Frederica formula (QTcF) interval (msec): value greater than (\>) 450, value \> 480, value \> 500, change from baseline \> 30 and \> 60. Baseline was defined as the last assessment prior to the date or time of the first dose of study treatment. In this outcome measure number of participants with overall ECG abnormalities are reported.
Time frame: From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Overall Electrocardiogram (ECG) Abnormalities: Phase I | 3 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Overall Electrocardiogram (ECG) Abnormalities: Phase I | 2 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Overall Electrocardiogram (ECG) Abnormalities: Phase I | 2 Participants |
Primary
Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I
The following hematology laboratory parameters were assessed: hemoglobin, hematocrit, platelets, white blood cells (WBC), neutrophils, lymphocytes, eosinophils, basophils, monocytes, WBC with automated 5-part differential, Red blood cells (RBC), absolute reticulocytes, reticulocytes percentage (%), Mean corpuscular hemoglobin (MCH), Mean corpuscular volume (MCV) and Red cell distribution width (RDW). Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants who had hematology parameter abnormality Grade \<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.
Time frame: Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: Neutrophils (10^9/L) decreased | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Neutrophils (10^9/L) decreased | 1 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Leukocytes (10^9/L) white blood cells decreased | 1 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: Leukocytes (10^9/L) white blood cells decreased | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Platelets (10^9/L) decreased | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Neutrophils (10^9/L) decreased | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Leukocytes (10^9/L) white blood cells decreased | 2 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: Leukocytes (10^9/L) white blood cells decreased | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: Neutrophils (10^9/L) decreased | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Platelets (10^9/L) decreased | 1 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Platelets (10^9/L) decreased | 2 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: Neutrophils (10^9/L) decreased | 3 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Leukocytes (10^9/L) white blood cells decreased | 1 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: Neutrophils (10^9/L) decreased | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v)5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: Leukocytes (10^9/L) white blood cells decreased | 2 Participants |
Primary
Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I
The following chemistry parameters were assessed: glucose, sodium, potassium, calcium, chloride, phosphate, bicarbonate, blood urea nitrogen or urea, creatinine, total protein, albumin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, indirect bilirubin, uric acid, calcium, magnesium, lactate dehydrogenase (LDH). Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death related to adverse event. Baseline was defined as last assessment prior to date/time of first dose of study treatment. Number of participants who had chemistry parameter abnormality Grade\<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.
Time frame: Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: ALT (U/L) increased | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: AST (U/L) increased | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: ALT (U/L) increased | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: AST (U/L) increased | 1 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 3: ALT (U/L) increased | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase I | Shift from baseline Grade to post-baseline Grade 4: AST (U/L) increased | 0 Participants |
Primary
Number of Participants With Treatment Discontinuations: Phase I
Number of participants with treatment discontinuations during the study treatment were reported in this outcome measure.
Time frame: During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 74.1 weeks for ontorpacept and 20.1 weeks for doxorubicin)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase I | Ontorpacept | 3 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase I | Doxorubicin | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase I | Ontorpacept | 3 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase I | Doxorubicin | 2 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase I | Ontorpacept | 3 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase I | Doxorubicin | 2 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I
An adverse event (AE) was any untoward medical occurrence or worsening of a pre-existing medical condition following or during exposure to pharmaceutical product, whether or not considered causally related to product. A serious adverse event (SAE) was an adverse event occurred during any study at any dose of the investigational products that fulfils one or more of following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs were those events with onset date occurred during on-treatment period. AEs included SAEs and all Non-SAEs. On-treatment period was defined as time from first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer therapy). Participant with at least one TEAE and one serious TEAEs are reported in this outcome measure.
Time frame: From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase I was 74.1 weeks; maximum follow up to approx. 78.1 weeks)
Population: The safety analysis set (SAS) included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I | Participants with TEAEs | 3 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I | Participants with Serious TEAEs | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I | Participants with TEAEs | 3 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I | Participants with Serious TEAEs | 1 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I | Participants with TEAEs | 3 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs: Phase I | Participants with Serious TEAEs | 1 Participants |
Primary
Objective Response Rate (ORR): Phase I and Phase II
ORR: percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator's assessment per response evaluation criteria in solid tumours RECIST version (v)1.1. BOR: best response recorded from start of treatment until disease progression (PD). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than(\< )10 mm. PR: at least 30 percent (%) decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. PD: at least 20% increase in sum of longest diameter of target lesions, taking as reference of the smallest sum on study.
Time frame: From the start of study treatment until disease progression (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Objective Response Rate (ORR): Phase I and Phase II | 0.0 Percentage of Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Objective Response Rate (ORR): Phase I and Phase II | 0.0 Percentage of Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Objective Response Rate (ORR): Phase I and Phase II | 33.3 Percentage of Participants |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Objective Response Rate (ORR): Phase I and Phase II | 18.8 Percentage of Participants |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Objective Response Rate (ORR): Phase I and Phase II | 0.0 Percentage of Participants |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Objective Response Rate (ORR): Phase I and Phase II | 4.5 Percentage of Participants |
Secondary
Disease Control Rate (DCR): Phase I and Phase II
DCR was defined as the percentage of participants who have achieved CR, PR, or SD lasting at least 4 weeks as per RECIST v1.1 CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: at least 30% decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum LD since treatment started. PD: at least 20% increase in sum of longest diameter of target lesions, taking as reference of the smallest sum on study.
Time frame: From the first dose of study treatment until PD or death, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Disease Control Rate (DCR): Phase I and Phase II | 66.7 Percentage of participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Disease Control Rate (DCR): Phase I and Phase II | 66.7 Percentage of participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Disease Control Rate (DCR): Phase I and Phase II | 66.7 Percentage of participants |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Disease Control Rate (DCR): Phase I and Phase II | 75.0 Percentage of participants |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Disease Control Rate (DCR): Phase I and Phase II | 84.6 Percentage of participants |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Disease Control Rate (DCR): Phase I and Phase II | 72.7 Percentage of participants |
Secondary
Duration of Disease Control (DDC): Phase I and Phase II
DDC: participants who achieved BOR of SD, as time from first ontorpacept infusion (Day1 of Cycle1) to date of documented PD/death of any cause. Calculated for participants who achieved CR,PR/SD lasting at least 4weeks. CR:disappearance of all target lesion. Any pathological lymph nodes must have reduction in short axis to\<10 mm. PR:at least 30%decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum LD since treatment started. PD:at least 20% increase in sum of LD of target lesion, taking reference of smallest sum on study. Participants without PD/death/with an event after 2/more missing/inadequate disease assessment/with event after start date of alternate anticancer therapy were censored at last response assessment date/last assessment prior to start date of alternate anti-cancer therapy, whichever is earlier.
Time frame: Time from first ontorpacept infusion (Day 1 of Cycle 1) to date of documented progression/death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Duration of Disease Control (DDC): Phase I and Phase II | 12.4 Months |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Duration of Disease Control (DDC): Phase I and Phase II | NA Months |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Duration of Disease Control (DDC): Phase I and Phase II | 10.6 Months |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Duration of Disease Control (DDC): Phase I and Phase II | 6.1 Months |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Duration of Disease Control (DDC): Phase I and Phase II | 4.7 Months |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Duration of Disease Control (DDC): Phase I and Phase II | 6.1 Months |
Secondary
Duration of Response (DOR): Phase I and Phase II
DOR was defined as time from date of first documented response (CR or PR) to date of documented progression or death of any cause after achieving response. DOR was calculated for participants who achieved CR or PR. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: at least 30% decrease in sum of longest diameter of target lesions, taking as reference baseline sum longest diameter. Participants without PD or death or participants with an event after 2 or more missing/inadequate disease assessment or participants with an event after the start date of alternate anticancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy, whichever is earlier.
Time frame: Time from date of first documented response (CR or PR) to date of documented progression or death of any cause after achieving response or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. Here Number of Participants Analyzed signifies participants who had CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Duration of Response (DOR): Phase I and Phase II | 9.7 Months |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Duration of Response (DOR): Phase I and Phase II | 4.7 Months |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Duration of Response (DOR): Phase I and Phase II | NA Months |
Secondary
Mean Change From Baseline in Blood Pressure: Phase II
Blood pressure included DBP and SBP. Mean change from baseline to safety follow up visit were reported in this outcome measure. Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1).
Time frame: Baseline, 30 and 60min post dose of C1D1,C1D8,C2D1,C3D1 and safety follow up 30 Days post last dose of study treatment/start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure of Phase II:88 weeks;maximum follow up:92 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. All participants reported under Number of Participants Analyzed contributed data to the table; however, may not have evaluable data for every row. Here, Number Analyzed signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C3D1 | -3.2 Millimeter of mercury | Standard Deviation 6.16 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C1D8 | -9.0 Millimeter of mercury | Standard Deviation 14.23 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C3D1 | -14.3 Millimeter of mercury | Standard Deviation 13.37 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C1D1 | -10.0 Millimeter of mercury | Standard Deviation 12.82 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C1D8 | -6.8 Millimeter of mercury | Standard Deviation 12.26 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C3D1 | -4.4 Millimeter of mercury | Standard Deviation 4.09 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C1D8 | -3.5 Millimeter of mercury | Standard Deviation 10.78 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C2D1 | -3.3 Millimeter of mercury | Standard Deviation 6.58 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at safety follow up | -2.3 Millimeter of mercury | Standard Deviation 12.1 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C1D1 | -2.8 Millimeter of mercury | Standard Deviation 7.46 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C2D1 | -3.8 Millimeter of mercury | Standard Deviation 7.27 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C3D1 | -14.1 Millimeter of mercury | Standard Deviation 12.2 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C1D1 | -5.0 Millimeter of mercury | Standard Deviation 12.18 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C2D1 | -9.1 Millimeter of mercury | Standard Deviation 14.57 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C1D8 | -1.8 Millimeter of mercury | Standard Deviation 9.08 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at safety follow up | -6.9 Millimeter of mercury | Standard Deviation 16.86 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C2D1 | -7.7 Millimeter of mercury | Standard Deviation 11.62 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C1D1 | -1.4 Millimeter of mercury | Standard Deviation 6.73 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C2D1 | -11.5 Millimeter of mercury | Standard Deviation 5.8 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C3D1 | -6.8 Millimeter of mercury | Standard Deviation 13.02 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C3D1 | -10.0 Millimeter of mercury | Standard Deviation 9.9 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C3D1 | -7.3 Millimeter of mercury | Standard Deviation 10.66 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C1D8 | -5.0 Millimeter of mercury | Standard Deviation 6.63 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C3D1 | -11.8 Millimeter of mercury | Standard Deviation 5.74 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C1D1 | -7.8 Millimeter of mercury | Standard Deviation 7.01 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at safety follow up | -1.3 Millimeter of mercury | Standard Deviation 13.52 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C1D8 | -4.8 Millimeter of mercury | Standard Deviation 5.81 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C1D1 | -8.8 Millimeter of mercury | Standard Deviation 5.37 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C1D8 | -7.0 Millimeter of mercury | Standard Deviation 16.52 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C1D8 | -9.5 Millimeter of mercury | Standard Deviation 14.54 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C1D1 | -15.4 Millimeter of mercury | Standard Deviation 15.06 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C2D1 | 0.8 Millimeter of mercury | Standard Deviation 8.3 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C2D1 | -3.5 Millimeter of mercury | Standard Deviation 8.23 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C2D1 | -3.3 Millimeter of mercury | Standard Deviation 19.29 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at safety follow up | -2.4 Millimeter of mercury | Standard Deviation 26.3 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C1D1 | -18.3 Millimeter of mercury | Standard Deviation 15.7 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C2D1 | -9.9 Millimeter of mercury | Standard Deviation 17.51 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C1D1 | -3.5 Millimeter of mercury | Standard Deviation 11.31 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C1D1 | -4.5 Millimeter of mercury | Standard Deviation 11.88 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C1D1 | -3.6 Millimeter of mercury | Standard Deviation 14.04 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C1D1 | -6.5 Millimeter of mercury | Standard Deviation 14.79 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C1D8 | 6.3 Millimeter of mercury | Standard Deviation 15.26 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C1D8 | 1.7 Millimeter of mercury | Standard Deviation 2.52 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C1D8 | 15.5 Millimeter of mercury | Standard Deviation 20.14 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C1D8 | 11.7 Millimeter of mercury | Standard Deviation 8.96 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C2D1 | -7.6 Millimeter of mercury | Standard Deviation 15.95 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C2D1 | -3.1 Millimeter of mercury | Standard Deviation 13.36 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C2D1 | -6.3 Millimeter of mercury | Standard Deviation 13.41 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 30 minutes post dose on C3D1 | -2.3 Millimeter of mercury | Standard Deviation 6.5 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at 60 minutes post dose on C3D1 | -2.0 Millimeter of mercury | Standard Deviation 1 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 30 minutes post dose on C3D1 | -7.3 Millimeter of mercury | Standard Deviation 20.5 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at 60 minutes post dose on C3D1 | -8.0 Millimeter of mercury | Standard Deviation 17.44 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | DBP: Change at safety follow up | 2.1 Millimeter of mercury | Standard Deviation 12.95 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Blood Pressure: Phase II | SBP: Change at safety follow up | 0.2 Millimeter of mercury | Standard Deviation 16.11 |
Secondary
Mean Change From Baseline in Body Weight: Phase II
Baseline was considered as the last measurement taken prior to the first infusion of study medication (Day 1 of Cycle 1)
Time frame: Baseline, Day 1 of Cycle 3, 5, 7 and safety follow up (up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest [maximum treatment exposure for Phase II was 88 weeks; maximum follow up to 92 weeks])
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment. All participants reported under Number of Participants Analyzed contributed data to the table; however, may not have evaluable data for every row. Here, Number Analyzed signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C3D1 | -1.30 Kilograms | Standard Deviation 1.765 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C5D1 | -1.23 Kilograms | Standard Deviation 2.348 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C7D1 | -0.84 Kilograms | Standard Deviation 2.836 |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at Follow up | -0.54 Kilograms | Standard Deviation 3.757 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at Follow up | 0.18 Kilograms | Standard Deviation 3.012 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C3D1 | -0.43 Kilograms | Standard Deviation 2.122 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C7D1 | 1.03 Kilograms | Standard Deviation 2.42 |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C5D1 | -1.03 Kilograms | Standard Deviation 2.807 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at Follow up | -3.55 Kilograms | Standard Deviation 5.018 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C5D1 | -2.44 Kilograms | Standard Deviation 2.62 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C7D1 | -2.57 Kilograms | Standard Deviation 3.695 |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Mean Change From Baseline in Body Weight: Phase II | Change at C3D1 | -1.83 Kilograms | Standard Deviation 1.637 |
Secondary
Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II
ECOG performance were classified as 5 grades: 0: fully active, able to carry on all pre-disease performance without restriction; 1: restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2: ambulatory and capable of all selfcare but unable to carry out any work activities, up and about more than 50% of waking hours; 3: capable of only limited selfcare, confined to bed or chair more than 50% of waking hours and 4: completely disabled, cannot carry on selfcare and totally confined to bed or chair. Higher score indicated lower health status. Worsening of ECOG was defined as a worsening from baseline (i.e., increase) in the ECOG assessment level and was recorded in two consecutive assessments.
Time frame: From Baseline up to 30 Days post last dose of study treatment/start of new anti-cancer therapy whichever occurred first (maximum exposure upto 74.1 and 88 weeks; maximum follow up to approx. 78.1 and 92 weeks for Phase I and II respectively)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II | 0 Participants |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II | 6 Participants |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II | 2 Participants |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Number of Participants With a Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status: Phase I and Phase II | 4 Participants |
Secondary
Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II
QOL was assessed with European organisation for research and treatment of cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) tool. The EORTC QLQ-C30 is self-administered, self-reported general cancer-specific questionnaire consisting of 30 items covered by one of 3 dimensions: global health status (2 items): functional scales(15 total items addressing either physical, emotional, cognitive/social functioning) and symptom scales(13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea/financial impact). Higher score indicated better overall QoL. Worsening of Global Health Status /QoL assessments was defined as at least a 10-point decrease from baseline in the standardized score (linear transformation) of Global Health Status/QoL.
Time frame: From Baseline up to 30 Days post last dose of study treatment/start of new anti-cancer therapy whichever occurred first (maximum exposure upto 74.1 and 88 weeks; maximum follow up to approx. 78.1 and 92 weeks for Phase I and II respectively)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II | 2 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II | 2 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II | 2 Participants |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II | 17 Participants |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II | 9 Participants |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Number of Participants With a Worsening of Global Health Status / Quality of Life (QoL) Status: Phase I and Phase II | 12 Participants |
Secondary
Number of Participants With Dose Modifications: Phase II
Dose modifications included dose reduction, dose omitted, infusion interruption and cycle delayed.
Time frame: During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 88 weeks for ontorpacept and 25 weeks for doxorubicin)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with cycle delayed- Doxorubicin | 8 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose reduction- Ontorpacept | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with cycle delayed- Ontorpacept | 15 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with infusion interruption- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose reduction- Doxorubicin | 11 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with infusion interruption- Ontorpacept | 2 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose omitted- Ontorpacept | 14 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose omitted- Doxorubicin | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with infusion interruption- Ontorpacept | 7 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose omitted- Ontorpacept | 7 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with infusion interruption- Doxorubicin | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose reduction- Ontorpacept | 5 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with cycle delayed- Doxorubicin | 4 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose omitted- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with cycle delayed- Ontorpacept | 5 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose reduction- Doxorubicin | 5 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with cycle delayed- Doxorubicin | 2 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose reduction- Ontorpacept | 17 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose omitted- Ontorpacept | 19 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with infusion interruption- Ontorpacept | 11 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose reduction- Doxorubicin | 13 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with dose omitted- Doxorubicin | 3 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with infusion interruption- Doxorubicin | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Dose Modifications: Phase II | Participants with cycle delayed- Ontorpacept | 5 Participants |
Secondary
Number of Participants With Overall ECG Abnormalities: Phase II
Standard 12- lead ECGs, average of triplicate assessments was obtained in participant in supine position and within 10 minutes total time. ECG abnormalities included: PR interval (msec): \>= 220 and change from baseline \>=20; QRS interval (msec) value \>=120; uncorrected QT interval, QT correct by QTcB interval and QT correct by QTcF interval (msec): value \> 450, value \> 480, value \> 500, change from baseline \> 30 and \> 60. Baseline was defined as the last assessment prior to the date or time of the first dose of study treatment. In this outcome measure number of participants with overall ECG abnormalities are reported.
Time frame: From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Overall ECG Abnormalities: Phase II | 17 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Overall ECG Abnormalities: Phase II | 8 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Overall ECG Abnormalities: Phase II | 11 Participants |
Secondary
Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II
The following chemistry parameters were assessed: glucose, sodium, potassium, calcium, chloride, phosphate, bicarbonate, blood urea nitrogen or urea, creatinine, total protein, albumin, alkaline phosphatase, AST, ALT, total bilirubin, indirect bilirubin, uric acid, calcium, magnesium and LDH. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death related to adverse event. Baseline was defined as last assessment prior to date/time of first dose of study treatment. Number of participants who had chemistry parameter abnormality Grade\<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.
Time frame: Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: ALT (U/L) increased | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Albumin; Hypoalbuminemia (g/L) | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Blood Bilirubin increased (umol/L) | 0 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Magnesium; Hypermagnesemia (mmol/L) | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Magnesium; Hypermagnesemia (mmol/L) | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: ALT (U/L) increased | 0 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Blood Bilirubin increased (umol/L) | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Albumin; Hypoalbuminemia (g/L) | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Magnesium; Hypermagnesemia (mmol/L) | 1 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Albumin; Hypoalbuminemia (g/L) | 1 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Blood Bilirubin increased (umol/L) | 0 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Chemistry Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: ALT (U/L) increased | 1 Participants |
Secondary
Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II
The following hematology laboratory parameters were assessed: hemoglobin, hematocrit, platelets, WBC, neutrophils, lymphocytes, eosinophils, basophils, monocytes, WBC with automated 5-part differential, RBC, absolute reticulocytes, reticulocytes %, MCH, MCV and RDW. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment. Number of participants who had hematology parameter abnormality Grade \<=2 at baseline and shifted to \>=3 post-baseline are reported in this outcome measure. Only non-zero categories for any reporting arm are reported.
Time frame: Baseline up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Leukocytes (10^9/L) white blood cells decreased | 12 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Leukocytes (10^9/L) white blood cells decreased | 12 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Neutrophils (10^9/L) decreased | 5 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Neutrophils (10^9/L) decreased | 21 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Platelets (10^9/L) decreased | 4 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Platelets (10^9/L) decreased | 2 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Platelets (10^9/L) decreased | 1 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Leukocytes (10^9/L) white blood cells decreased | 3 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Neutrophils (10^9/L) decreased | 10 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Platelets (10^9/L) decreased | 6 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Leukocytes (10^9/L) white blood cells decreased | 9 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Neutrophils (10^9/L) decreased | 2 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Leukocytes (10^9/L) white blood cells decreased | 12 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Neutrophils (10^9/L) decreased | 6 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Platelets (10^9/L) decreased | 7 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 4: Neutrophils (10^9/L) decreased | 8 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Leukocytes (10^9/L) white blood cells decreased | 7 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Shift in NCI-CTCAE v5.0 Grade <=2 at Baseline to >=3 Post-baseline in Hematology Parameters: Phase II | Shift from baseline Grade to post-baseline Grade 3: Platelets (10^9/L) decreased | 12 Participants |
Secondary
Number of Participants With TEAEs and Serious TEAEs: Phase II
An AE was any untoward medical occurrence or worsening of a pre-existing medical condition following or during exposure to pharmaceutical product, whether or not considered causally related to product. A SAE was an adverse event occurred during any study at any dose of the investigational products that fulfils one or more of following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs were those events with onset date occurred during on-treatment period. AEs included SAEs and all Non-SAEs. On-treatment period was defined as time from first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer therapy). Participant with at least one TEAE and one serious TEAEs are reported in this outcome measure.
Time frame: From first dose of study treatment (Day 1) up to 30 Days post last dose of study treatment or start of new anti-cancer therapy whichever occurred soonest (maximum treatment exposure for Phase II was 88 weeks; maximum follow up to approx. 92 weeks)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With TEAEs and Serious TEAEs: Phase II | Participants with TEAEs | 32 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With TEAEs and Serious TEAEs: Phase II | Participants with Serious TEAEs | 9 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With TEAEs and Serious TEAEs: Phase II | Participants with TEAEs | 13 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With TEAEs and Serious TEAEs: Phase II | Participants with Serious TEAEs | 8 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With TEAEs and Serious TEAEs: Phase II | Participants with TEAEs | 22 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With TEAEs and Serious TEAEs: Phase II | Participants with Serious TEAEs | 15 Participants |
Secondary
Number of Participants With Treatment Discontinuations: Phase II
Number of participants with treatment discontinuations during the study treatment were reported in this outcome measure.
Time frame: During study treatment (from first dose of study treatment [Day 1] to maximum treatment exposure of 88 weeks for ontorpacept and 25 weeks for doxorubicin)
Population: The SAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase II | Ontorpacept | 32 Participants |
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase II | Doxorubicin | 15 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase II | Ontorpacept | 13 Participants |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase II | Doxorubicin | 5 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase II | Ontorpacept | 22 Participants |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Number of Participants With Treatment Discontinuations: Phase II | Doxorubicin | 10 Participants |
Secondary
Overall Survival (OS): Phase I and Phase II
OS was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to death of any cause. Participants last known to be alive were censored at their last known alive date. Kaplan-Meier method was used for analysis.
Time frame: From the first ontorpacept infusion (Day 1 of Cycle 1) to death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Overall Survival (OS): Phase I and Phase II | NA Months |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Overall Survival (OS): Phase I and Phase II | 8.2 Months |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Overall Survival (OS): Phase I and Phase II | NA Months |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Overall Survival (OS): Phase I and Phase II | 20.5 Months |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Overall Survival (OS): Phase I and Phase II | NA Months |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Overall Survival (OS): Phase I and Phase II | 14.4 Months |
Secondary
Progression Free Survival (PFS): Phase I and Phase II
PFS was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause, whichever occurred first. PD was defined at least 20% increase in sum of longest diameter (LD) of target lesion, taking reference of smallest sum on study. Participants without PD or death or participants with an event after 2 or more missing/inadequate disease assessment or participants with an event after the start date of alternate anticancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy, whichever is earlier. Kaplan-Meier method was used for analysis.
Time frame: Time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause or censoring, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Progression Free Survival (PFS): Phase I and Phase II | 7.9 Months |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Progression Free Survival (PFS): Phase I and Phase II | 6.4 Months |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Progression Free Survival (PFS): Phase I and Phase II | 7.6 Months |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Progression Free Survival (PFS): Phase I and Phase II | 6.0 Months |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Progression Free Survival (PFS): Phase I and Phase II | 4.3 Months |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Progression Free Survival (PFS): Phase I and Phase II | 5.6 Months |
Secondary
Time to New Metastases: Phase I and Phase II
Time to new metastasis was defined as the time from the ontorpacept infusion (Day 1 of Cycle 1) to a new lesion appearance. Participants without new lesion or participants with new metastases after 2 or more missing/inadequate disease assessment or participants with new metastases after the start date of alternate anti-cancer therapy were censored at their last response assessment date or last assessment prior to the start date of alternate anti-cancer therapy whichever was earlier.
Time frame: Time from the first ontorpacept infusion (Day 1 of Cycle 1) until the appearance of new lesion or death or censoring date, whichever occurred first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Time to New Metastases: Phase I and Phase II | NA Months |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Time to New Metastases: Phase I and Phase II | NA Months |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Time to New Metastases: Phase I and Phase II | NA Months |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Time to New Metastases: Phase I and Phase II | NA Months |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Time to New Metastases: Phase I and Phase II | 4.7 Months |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Time to New Metastases: Phase I and Phase II | NA Months |
Secondary
Time to Progression (TTP): Phase I and Phase II
TTP was defined as the time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause, whichever is first; provided death was not considered as an event. PD: at least 20% increase in sum of longest diameter of target lesion, taking reference of smallest sum on study. Participants without PD or death or with an event after 2 or more missing or inadequate disease assessment or with event after start date of alternate anticancer therapy were censored at last response assessment date or last assessment prior to start date of alternate anti-cancer therapy, whichever is earlier.
Time frame: Time from the first ontorpacept infusion (Day 1 of Cycle 1) to PD or death of any cause or censoring, whichever is first (maximum exposure up to 74.1 weeks for Phase I and 88 weeks for Phase II)
Population: The FAS included all participants who were enrolled, allocated to treatment, and received at least one non-zero dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: Ontorpacept 0.2 mg/kg + Doxorubicin | Time to Progression (TTP): Phase I and Phase II | 7.9 Months |
| Phase I: Ontorpacept 0.7 mg/kg + Doxorubicin | Time to Progression (TTP): Phase I and Phase II | 6.4 Months |
| Phase I: Ontorpacept 2.0 mg/kg + Doxorubicin | Time to Progression (TTP): Phase I and Phase II | 7.6 Months |
| Phase II: Ontorpacept 0.2 mg/kg + Doxorubicin (Cohort A) | Time to Progression (TTP): Phase I and Phase II | 6.0 Months |
| Phase II: Ontorpacept 1.0 mg/kg + Doxorubicin (Cohort C) | Time to Progression (TTP): Phase I and Phase II | 4.3 Months |
| Phase II: Ontorpacept 2.0 mg/kg + Doxorubicin (Cohort B) | Time to Progression (TTP): Phase I and Phase II | 5.6 Months |