Advanced Solid Tumors, Head and Neck Cancer, Pancreatic Cancer, Ovarian Cancer, Renal Cell Carcinoma, Malignant Glioma, Non-small Cell Lung Cancer
Conditions
Brief summary
Phase 1a/1b does-escalation study of cabiralizumab alone and with nivolumab in advanced solid tumors.
Detailed description
This is a phase 1a/b single-arm, open-label study to evaluate safety, tolerability, pharmacokinetics (PK), and clinical benefit of cabiralizumab in combination with nivolumab in patients with selected advanced cancers.
Interventions
BIOLOGICALCabiralizumab
Solution for IV administration
BIOLOGICALNivolumab
Solution for IV administration
Sponsors
Bristol-Myers Squibb
Five Prime Therapeutics, Inc.
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
* Patients must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. * Patients must have had progressive disease on, after, or refused, appropriate approved therapy for their tumor type. * Patients must have histologically or cytologically confirmed solid tumor that is locally recurrent or metastatic and has progressed following standard treatment or is not appropriate for standard treatment * Understand and sign an Institutional review board/Independent ethics committee (IRB/IEC)-approved informed consent form (ICF) prior to any study-specific evaluation * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Willing and able to comply with all study procedures
Exclusion criteria
* Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum creatine kinase (CK) levels * Decreased cardiac function with New York Heart Association (NYHA) \> Class 2 * Uncontrolled or significant heart disorder such as unstable angina * Significant abnormalities on electrocardiogram (ECG) at screening. Fridericia's correction formula for QT interval (QTcF) \> 450 msec for males or \> 470 msec for females at screening * History of anti-drug antibodies, severe allergic, anaphylactic, or other infusion-related reaction to a previous biologic agent * Positive test for latent tuberculosis (TB) at screening (Quantiferon test) or evidence of active TB * Patients with abnormal serum chemistry values, which in the opinion of the Investigator is considered to be clinically significant, will be excluded from the study * Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples * Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results * Pregnant or breastfeeding * Current unresolved infection or history of chronic, active, clinically significant infection (viral, bacterial, fungal, or other) which, in the opinion of the Investigator, would preclude the patient from exposure to a biologic agent or pose a risk to patient safety * Prior exposure to any colony stimulating factor 1 receptor (CSF1R) pathway inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | 28 days | A DLT was defined as a study drug-related ≥ Grade 3 AE (using National Cancer Institute Common Terminology Criteria for Adverse Events v 4.03) occurring during the first 28-days, excluding Grade 3 tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor), rash, immune-related adverse event (irAE) that resolved to ≤ Grade 1 by 14 days or a transient (resolving within 6 hours of onset) Grade 3 infusion-related AE. Any recurrence of Grade 3 rash, irAE or infusion-related AE was considered a DLT. The protocol was amended such that in the absence of clinical symptoms and other accompanying changes in bilirubin or alanine aminotransferase (ALT), serum elevation of aspartate aminotransferase (AST)/ALT \> 12 × upper limit of normal (ULN) and ≤ 20 × ULN that lasted for \< 7 days and serum elevation of creatine kinase (CK) and/or lactate dehydrogenase (LDH) \> 15 × ULN and ≤ 20 × ULN that lasted for \< 7 days were not considered DLTs. |
| Recommended Dose (RD) of Cabiralizumab in Combination With Nivolumab (Phase 1a) | 28 days | Using both the incidence of dose limiting toxicities (first 28 days on therapy) as well as overall tolerability and toxicities observed beyond 28 days, the RD was chosen as 4 mg/kg of cabiralizumab + 3 mg/kg nivolumab every 2 weeks to be the dose used in the Phase 1b (dose expansion). No maximum tolerated dose was identified. |
| Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | From first dose of study drug up to 100 days after last dose. Median (range) duration of exposure was 6 (2-32) weeks in the monotherapy cohorts and 8 (2-108) weeks for cabiralizumab and 8 (2-156) weeks for nivolumab in the combination groups. | An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation, patient-administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or causes prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Was an important medical event that may jeopardize the patient or may require intervention (e.g., medical, surgical) to prevent one of the other serious outcomes listed in the definition above. |
| Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b) | From first dose of study drug up to last dose; median (range) duration of exposure was 8 (2-108) weeks for cabiralizumab and 8 (2-156) weeks for nivolumab. | Safety: In the Phase 1b only, the incidence of treatment discontinuations, modifications, and interruptions due to adverse events. |
| Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | Tumor response was assessed every 8 weeks from first dose for the first 12 months and then every 12 weeks thereafter until end of treatment; maximum duration of treatment was 156 weeks. | Objective response rate (ORR) is defined as the percentage of participants with confirmed responses of either complete response (CR) or partial response (PR). Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 by investigator review. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycles 1 and 8, Day 1 predose, and at 0.25, 4, 24, 72, 168, and 336 hours after the end of infusion. | Cabiralizumab serum concentration was determined using a validated enzyme-linked immunosorbent assay (ELISA) method. |
| PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cycles 1 and 8, Day 1 predose, and at 0.25, 4, 24, 72, 168, and 336 hours after the end of infusion. | Cabiralizumab serum concentration was determined using a validated enzyme-linked immunosorbent assay method. Cmax is the maximum observed serum concentration of cabiralizumab during the dosing period. Cmin is the minimum observed serum concentration of cabiralizumab during a dosing interval (excluding pre-dose concentration before the first dose). |
| Efficacy: Overall Survival (Phase 1b) | From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months. | Overall survival (OS) was defined as the time from first dose of study drug to death due to any cause. OS was calculated using the Kaplan-Meier method. Participants who did not die while on study were censored on the date they were last known to be alive. |
| Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Blood samples were collected before the infusion on Cycles 1 (Baseline), 2, 3, 4, 5, 9, 13, and 21, and at 28 days and 100 days after the end of treatment | Anti-drug antibodies (ADA) to nivolumab in serum were measured by a validated electrochemiluminescence assay. Baseline ADA Positive is defined as participants who had a baseline ADA sample which tested as positive for an anti-drug antibody against cabiralizumab; Post baseline ADA Positive is defined as participants that either had 1) an ADA detected (positive seroconversion) sample in a participant for whom ADA was not detected at baseline, or (2) an ADA detected sample with ADA titer at least 4-fold or greater than the baseline positive titer; Post baseline ADA Negative: Participants who never reported an ADA-positive sample after the initiation of treatment. |
| Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Blood samples were collected before the infusion on Cycles 1 (Baseline), 2, 3, 4, 5, 9, 13, and 21, and at 28 days and 100 days after the end of treatment | Anti-drug antibodies (ADA) to cabiralizumab in serum were measured by a validated bridging electrochemiluminescence assay (ECLA). Baseline ADA Positive is defined as participants who had a baseline ADA sample which tested as positive for an anti-drug antibody against cabiralizumab; Post baseline ADA Positive is defined as participants that either had 1) an ADA detected (positive seroconversion) sample in a participant for whom ADA was not detected at baseline, or (2) an ADA detected sample with ADA titer at least 4-fold or greater than the baseline positive titer; Post baseline ADA Negative: Participants who never reported an ADA-positive sample after the initiation of treatment. |
| Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 52 weeks | Overall survival at one-year is defined as the percentage of participants who were alive one year after receiving their first dose of study drug. |
| Efficacy: Duration of Response (Phase 1b) | From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months. | Duration of response (DOR) is defined as the time from the date of the first documentation of confirmed response (CR or PR) to the first objective documentation of progressive disease (PD) per RECIST v1.1 per Investigator assessment or to death due to any cause in the absence of documented PD. DOR was analyzed using Kaplan-Meier methods. Participants who discontinued from the study, did not die or have disease progression, or who received new anticancer therapy were censored on the date of last evaluable assessment prior to initiation of subsequent therapy. Participants with no evaluable baseline or post-baseline assessments were censored on the date of first dose. Progressive Disease (PD): The appearance of one or more new lesions or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Efficacy: Progression Free Survival (Phase 1b) | From first dose of study drug up to the end of study; maximum time on study in phase 1b was 35.9 months. | Progression-free survival (PFS) was defined as as the time from the first dose to the first objectively documented disease progression per RECIST v1.1 per Investigator assessment or death due to any cause in the absence of documented progressive disease (PD). PFS was analyzed using Kaplan-Meier methods. Participants who discontinued from the study, did not die or have disease progression, or who received new anticancer therapy were censored on the date of last evaluable assessment prior to initiation of subsequent therapy. Participants with no evaluable baseline or post-baseline assessments were censored on the date of first dose. |
| Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | Tumor response was assessed every 8 weeks from first dose for the first 12 months and then every 12 weeks thereafter until end of treatment; maximum duration of treatment was 156 weeks. | Objective response rate is defined as the percentage of participants with confirmed responses of either complete response (CR) or partial response (PR). Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 by independent central review. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Countries
United States
Participant flow
Recruitment details
This study included a Phase 1a dose escalation and a Phase 1b dose expansion. The dose escalation phase consisted of cabiralizumab monotherapy cohorts and cohorts of cabiralizumab in combination with nivolumab. All dose escalation decisions were based on assessment of dose-limiting toxicity (DLT), overall safety, and tolerability. Enrollment in Phase 1b expansion began after a recommended dose had been identified in Phase 1a.
Pre-assignment details
The primary objective of the study was to assess the safety and tolerability of cabiralizumab alone and in combination with nivolumab. Accordingly, the safety results are grouped by patients who received the same dose and schedule of both medications. The co-primary objective for the Phase 1b portion was to evaluate the clinical benefit. Accordingly, the efficacy results from Phase 1b are reported by tumor types.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1a: Cabiralizumab 2 mg/kg Participants received 2 mg/kg cabiralizumab administered intravenously (IV) once every 2 weeks (Q2W) until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 3 |
| Phase 1a: Cabiralizumab 4 mg/kg Participants received 4 mg/kg cabiralizumab IV Q2W until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 10 |
| Phase 1a: Cabiralizumab 6 mg/kg Participants received 6 mg/kg cabiralizumab IV Q2W until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 11 |
| Phase 1a: Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W Participants received 1 mg/kg cabiralizumab IV and 3 mg/kg nivolumab IV Q2W until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 4 |
| Phase 1a: Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W Participants received 2 mg/kg cabiralizumab IV and 3 mg/kg nivolumab IV Q2W until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 3 |
| Phase 1a: Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W Participants received 4 mg/kg cabiralizumab IV and 3 mg/kg nivolumab IV Q2W until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 3 |
| Phase 1a: Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W Participants received 6 mg/kg cabiralizumab IV and 3 mg/kg nivolumab IV Q2W until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 6 |
| Phase 1a: Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W Participants received 4 mg/kg cabiralizumab IV and 3 mg/kg nivolumab IV every 3 weeks (Q3W) until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 10 |
| Phase 1b: Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W Participants received 4 mg/kg cabiralizumab IV and 3 mg/kg nivolumab IV Q2W until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. | 262 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrew Consent Before Receiving Study Treatment | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Phase 1a: Cabiralizumab 4 mg/kg | Phase 1a: Cabiralizumab 6 mg/kg | Phase 1a: Cabiralizumab 2 mg/kg | Phase 1a: Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Phase 1a: Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Phase 1a: Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Phase 1a: Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Phase 1a: Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Phase 1b: Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 153 Participants | 5 Participants | 6 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 6 Participants | 121 Participants |
| Age, Categorical Between 18 and 65 years | 159 Participants | 5 Participants | 5 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 141 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 276 Participants | 10 Participants | 11 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 6 Participants | 10 Participants | 231 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized American Indian / Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 12 Participants |
| Race/Ethnicity, Customized Black | 18 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 17 Participants |
| Race/Ethnicity, Customized Native Hawaiian / Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 13 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 13 Participants |
| Race/Ethnicity, Customized White | 267 Participants | 10 Participants | 10 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 10 Participants | 219 Participants |
| Sex: Female, Male Female | 151 Participants | 6 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 6 Participants | 125 Participants |
| Sex: Female, Male Male | 161 Participants | 4 Participants | 8 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 6 / 10 | 6 / 11 | 2 / 4 | 3 / 4 | 172 / 265 | 4 / 6 | 7 / 10 |
| other Total, other adverse events | 2 / 3 | 10 / 11 | 10 / 10 | 4 / 4 | 3 / 3 | 264 / 265 | 6 / 6 | 9 / 10 |
| serious Total, serious adverse events | 1 / 3 | 1 / 10 | 6 / 11 | 2 / 4 | 1 / 3 | 138 / 265 | 3 / 6 | 5 / 10 |
Outcome results
Primary
Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b)
Objective response rate (ORR) is defined as the percentage of participants with confirmed responses of either complete response (CR) or partial response (PR). Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 by investigator review. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Tumor response was assessed every 8 weeks from first dose for the first 12 months and then every 12 weeks thereafter until end of treatment; maximum duration of treatment was 156 weeks.
Population: Response-evaluable population based on investigator assessment included all participants who had a measurable lesion at baseline and had at least 1 post-baseline tumor assessment, or clinical progression, or death.~Efficacy endpoints were specified to be analyzed by disease type for Phase 1b participants only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | 6.9 percentage of participants |
| Cabiralizumab 4 mg/kg Q2W | Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | 3.2 percentage of participants |
| Cabiralizumab 6 mg/kg Q2W | Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | 13.8 percentage of participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | 5.9 percentage of participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | 13.3 percentage of participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | 6.7 percentage of participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | 0 percentage of participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Efficacy: Objective Response Rate - Investigator Assessment (Phase 1b) | 9.1 percentage of participants |
Primary
Recommended Dose (RD) of Cabiralizumab in Combination With Nivolumab (Phase 1a)
Using both the incidence of dose limiting toxicities (first 28 days on therapy) as well as overall tolerability and toxicities observed beyond 28 days, the RD was chosen as 4 mg/kg of cabiralizumab + 3 mg/kg nivolumab every 2 weeks to be the dose used in the Phase 1b (dose expansion). No maximum tolerated dose was identified.
Time frame: 28 days
Population: Participants enrolled in the dose escalation phase who received at least 2 doses of study drug during the 28-day evaluation interval or who discontinued study treatment for drug-related adverse events before receiving 2 doses of study drug were considered evaluable for DLT determination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Recommended Dose (RD) of Cabiralizumab in Combination With Nivolumab (Phase 1a) | 4 mg/kg Q2W |
Primary
Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b)
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation, patient-administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or causes prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Was an important medical event that may jeopardize the patient or may require intervention (e.g., medical, surgical) to prevent one of the other serious outcomes listed in the definition above.
Time frame: From first dose of study drug up to 100 days after last dose. Median (range) duration of exposure was 6 (2-32) weeks in the monotherapy cohorts and 8 (2-108) weeks for cabiralizumab and 8 (2-156) weeks for nivolumab in the combination groups.
Population: All participants who received at least 1 dose of cabiralizumab and/or nivolumab. Safety results are grouped by participants who received the same treatment regimen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Any adverse event | 2 Participants |
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Serious adverse events | 1 Participants |
| Cabiralizumab 4 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Serious adverse events | 1 Participants |
| Cabiralizumab 4 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Any adverse event | 10 Participants |
| Cabiralizumab 6 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Any adverse event | 10 Participants |
| Cabiralizumab 6 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Serious adverse events | 6 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Serious adverse events | 2 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Any adverse event | 4 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Any adverse event | 3 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Serious adverse events | 1 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Any adverse event | 264 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Serious adverse events | 138 Participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Any adverse event | 6 Participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Serious adverse events | 3 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Serious adverse events | 5 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Safety: Number of Participants With Adverse Events and Serious Adverse Events (Phase 1a and 1b) | Any adverse event | 10 Participants |
Primary
Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a)
A DLT was defined as a study drug-related ≥ Grade 3 AE (using National Cancer Institute Common Terminology Criteria for Adverse Events v 4.03) occurring during the first 28-days, excluding Grade 3 tumor flare (defined as local pain, irritation, or rash localized at sites of known or suspected tumor), rash, immune-related adverse event (irAE) that resolved to ≤ Grade 1 by 14 days or a transient (resolving within 6 hours of onset) Grade 3 infusion-related AE. Any recurrence of Grade 3 rash, irAE or infusion-related AE was considered a DLT. The protocol was amended such that in the absence of clinical symptoms and other accompanying changes in bilirubin or alanine aminotransferase (ALT), serum elevation of aspartate aminotransferase (AST)/ALT \> 12 × upper limit of normal (ULN) and ≤ 20 × ULN that lasted for \< 7 days and serum elevation of creatine kinase (CK) and/or lactate dehydrogenase (LDH) \> 15 × ULN and ≤ 20 × ULN that lasted for \< 7 days were not considered DLTs.
Time frame: 28 days
Population: Participants enrolled in the dose escalation phase who received at least 2 doses of study drug during the 28-day evaluation interval or who discontinued study treatment for drug-related adverse events before receiving 2 doses of study drug were considered evaluable for DLT determination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 CK increase | 0 Participants |
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 AST increase | 0 Participants |
| Cabiralizumab 4 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 AST increase | 2 Participants |
| Cabiralizumab 4 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 CK increase | 0 Participants |
| Cabiralizumab 6 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 AST increase | 1 Participants |
| Cabiralizumab 6 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 CK increase | 1 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 AST increase | 0 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 CK increase | 0 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 CK increase | 0 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 AST increase | 0 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 CK increase | 0 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 AST increase | 0 Participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 AST increase | 0 Participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) | Grade 3 CK increase | 0 Participants |
Primary
Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b)
Safety: In the Phase 1b only, the incidence of treatment discontinuations, modifications, and interruptions due to adverse events.
Time frame: From first dose of study drug up to last dose; median (range) duration of exposure was 8 (2-108) weeks for cabiralizumab and 8 (2-156) weeks for nivolumab.
Population: All participants who received at least 1 dose of cabiralizumab and/or nivolumab at the RD of 4 mg/kg cabiralizumab + 3 mg/kg nivolumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b) | Cabiralizumab infusion modifications | 12 Participants |
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b) | Nivolumab infusion interruptions | 4 Participants |
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b) | Nivolumab infusion modifications | 8 Participants |
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b) | AEs leading to discontinuation of cabiralizumab or nivolumab | 54 Participants |
| Cabiralizumab 2 mg/kg Q2W | Safety: Number of Participants With Treatment Discontinuations, Modifications, or Interruptions Due to Adverse Events (Phase 1b) | Cabiralizumab infusion interruptions | 0 Participants |
Secondary
Efficacy: Duration of Response (Phase 1b)
Duration of response (DOR) is defined as the time from the date of the first documentation of confirmed response (CR or PR) to the first objective documentation of progressive disease (PD) per RECIST v1.1 per Investigator assessment or to death due to any cause in the absence of documented PD. DOR was analyzed using Kaplan-Meier methods. Participants who discontinued from the study, did not die or have disease progression, or who received new anticancer therapy were censored on the date of last evaluable assessment prior to initiation of subsequent therapy. Participants with no evaluable baseline or post-baseline assessments were censored on the date of first dose. Progressive Disease (PD): The appearance of one or more new lesions or at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months.
Population: Phase 1b response-evaluable population based on investigator assessment with documented CR or PR.~Efficacy endpoints were specified to be analyzed by disease type for Phase 1b participants only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Efficacy: Duration of Response (Phase 1b) | 8.9 months |
| Cabiralizumab 4 mg/kg Q2W | Efficacy: Duration of Response (Phase 1b) | 16.2 months |
| Cabiralizumab 6 mg/kg Q2W | Efficacy: Duration of Response (Phase 1b) | NA months |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Duration of Response (Phase 1b) | 12.7 months |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Duration of Response (Phase 1b) | 7.3 months |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Duration of Response (Phase 1b) | NA months |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Efficacy: Duration of Response (Phase 1b) | NA months |
Secondary
Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b)
Objective response rate is defined as the percentage of participants with confirmed responses of either complete response (CR) or partial response (PR). Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 by independent central review. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Tumor response was assessed every 8 weeks from first dose for the first 12 months and then every 12 weeks thereafter until end of treatment; maximum duration of treatment was 156 weeks.
Population: Response-evaluable population based on central review assessment included all participants who had at least 1 post-baseline tumor assessment, or clinical progression, or death.~Efficacy endpoints were specified to be analyzed by disease type for phase 1b participants only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | 3.4 percentage of participants |
| Cabiralizumab 4 mg/kg Q2W | Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | 0 percentage of participants |
| Cabiralizumab 6 mg/kg Q2W | Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | 10.7 percentage of participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | 6.0 percentage of participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | 6.7 percentage of participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | 16.7 percentage of participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | 0 percentage of participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b) | 9.1 percentage of participants |
Secondary
Efficacy: Overall Survival (OS) at One Year (Phase 1b)
Overall survival at one-year is defined as the percentage of participants who were alive one year after receiving their first dose of study drug.
Time frame: 52 weeks
Population: All treated participants in Phase 1b; Efficacy endpoints were specified to be analyzed by disease type for phase 1b participants only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 51.1 percentage of participants |
| Cabiralizumab 4 mg/kg Q2W | Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 29.2 percentage of participants |
| Cabiralizumab 6 mg/kg Q2W | Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 42.5 percentage of participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 27.2 percentage of participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 52.9 percentage of participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 77.8 percentage of participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 35.0 percentage of participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Efficacy: Overall Survival (OS) at One Year (Phase 1b) | 36.4 percentage of participants |
Secondary
Efficacy: Overall Survival (Phase 1b)
Overall survival (OS) was defined as the time from first dose of study drug to death due to any cause. OS was calculated using the Kaplan-Meier method. Participants who did not die while on study were censored on the date they were last known to be alive.
Time frame: From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months.
Population: All treated participants in Phase 1b; Efficacy endpoints were specified to be analyzed by disease type for phase 1b participants only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Efficacy: Overall Survival (Phase 1b) | 12.3 months |
| Cabiralizumab 4 mg/kg Q2W | Efficacy: Overall Survival (Phase 1b) | 4.7 months |
| Cabiralizumab 6 mg/kg Q2W | Efficacy: Overall Survival (Phase 1b) | 6.4 months |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Overall Survival (Phase 1b) | 5.6 months |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Overall Survival (Phase 1b) | 13.9 months |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Overall Survival (Phase 1b) | NA months |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Overall Survival (Phase 1b) | 8.1 months |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Efficacy: Overall Survival (Phase 1b) | 5.3 months |
Secondary
Efficacy: Progression Free Survival (Phase 1b)
Progression-free survival (PFS) was defined as as the time from the first dose to the first objectively documented disease progression per RECIST v1.1 per Investigator assessment or death due to any cause in the absence of documented progressive disease (PD). PFS was analyzed using Kaplan-Meier methods. Participants who discontinued from the study, did not die or have disease progression, or who received new anticancer therapy were censored on the date of last evaluable assessment prior to initiation of subsequent therapy. Participants with no evaluable baseline or post-baseline assessments were censored on the date of first dose.
Time frame: From first dose of study drug up to the end of study; maximum time on study in phase 1b was 35.9 months.
Population: All treated participants in Phase 1b; Efficacy endpoints were specified to be analyzed by disease type for phase 1b participants only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Efficacy: Progression Free Survival (Phase 1b) | 2.8 months |
| Cabiralizumab 4 mg/kg Q2W | Efficacy: Progression Free Survival (Phase 1b) | 1.9 months |
| Cabiralizumab 6 mg/kg Q2W | Efficacy: Progression Free Survival (Phase 1b) | 1.8 months |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Progression Free Survival (Phase 1b) | 1.7 months |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Progression Free Survival (Phase 1b) | 2.0 months |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Progression Free Survival (Phase 1b) | 2.9 months |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Efficacy: Progression Free Survival (Phase 1b) | 1.8 months |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Efficacy: Progression Free Survival (Phase 1b) | 1.8 months |
Secondary
Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b)
Anti-drug antibodies (ADA) to cabiralizumab in serum were measured by a validated bridging electrochemiluminescence assay (ECLA). Baseline ADA Positive is defined as participants who had a baseline ADA sample which tested as positive for an anti-drug antibody against cabiralizumab; Post baseline ADA Positive is defined as participants that either had 1) an ADA detected (positive seroconversion) sample in a participant for whom ADA was not detected at baseline, or (2) an ADA detected sample with ADA titer at least 4-fold or greater than the baseline positive titer; Post baseline ADA Negative: Participants who never reported an ADA-positive sample after the initiation of treatment.
Time frame: Blood samples were collected before the infusion on Cycles 1 (Baseline), 2, 3, 4, 5, 9, 13, and 21, and at 28 days and 100 days after the end of treatment
Population: All participants who received at least 1 dose of cabiralizumab and had available ADA data at baseline and post-baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 2 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-negative | 3 Participants |
| Cabiralizumab 2 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 2 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-negative | 3 Participants |
| Cabiralizumab 4 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-negative | 7 Participants |
| Cabiralizumab 4 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-negative | 9 Participants |
| Cabiralizumab 4 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-positive | 1 Participants |
| Cabiralizumab 4 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-positive | 1 Participants |
| Cabiralizumab 6 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 6 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-negative | 10 Participants |
| Cabiralizumab 6 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-negative | 11 Participants |
| Cabiralizumab 6 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-negative | 4 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-negative | 3 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-negative | 3 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-negative | 3 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-negative | 223 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-positive | 26 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-negative | 254 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-positive | 9 Participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-negative | 6 Participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-positive | 0 Participants |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-negative | 6 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-negative | 9 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-positive | 3 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Cabiralizumab ADA-negative | 6 Participants |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b) | Baseline cabiralizumab ADA-positive | 1 Participants |
Secondary
Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b)
Anti-drug antibodies (ADA) to nivolumab in serum were measured by a validated electrochemiluminescence assay. Baseline ADA Positive is defined as participants who had a baseline ADA sample which tested as positive for an anti-drug antibody against cabiralizumab; Post baseline ADA Positive is defined as participants that either had 1) an ADA detected (positive seroconversion) sample in a participant for whom ADA was not detected at baseline, or (2) an ADA detected sample with ADA titer at least 4-fold or greater than the baseline positive titer; Post baseline ADA Negative: Participants who never reported an ADA-positive sample after the initiation of treatment.
Time frame: Blood samples were collected before the infusion on Cycles 1 (Baseline), 2, 3, 4, 5, 9, 13, and 21, and at 28 days and 100 days after the end of treatment
Population: All participants who received at least 1 dose of nivolumab and had available ADA data at baseline and post-baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-positive | 1 Participants |
| Cabiralizumab 2 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-negative | 4 Participants |
| Cabiralizumab 2 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-positive | 0 Participants |
| Cabiralizumab 2 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-negative | 2 Participants |
| Cabiralizumab 4 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-negative | 3 Participants |
| Cabiralizumab 4 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-positive | 0 Participants |
| Cabiralizumab 4 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-positive | 0 Participants |
| Cabiralizumab 4 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-negative | 3 Participants |
| Cabiralizumab 6 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-positive | 26 Participants |
| Cabiralizumab 6 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-negative | 235 Participants |
| Cabiralizumab 6 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-positive | 57 Participants |
| Cabiralizumab 6 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-negative | 192 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-positive | 1 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-negative | 6 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-positive | 0 Participants |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-negative | 5 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-positive | 3 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-negative | 8 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Nivolumab ADA-negative | 6 Participants |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b) | Baseline nivolumab ADA-positive | 2 Participants |
Secondary
Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b)
Cabiralizumab serum concentration was determined using a validated enzyme-linked immunosorbent assay (ELISA) method.
Time frame: Cycles 1 and 8, Day 1 predose, and at 0.25, 4, 24, 72, 168, and 336 hours after the end of infusion.
Population: The PK evaluable population included participants who received at least 1 dose of cabiralizumab, had at least 1 available serum concentration data, and adequate PK assessments which could be used to reliably derive at least 1 PK parameter. Not all participants completed 8 cycles.~PK data are reported by treatment regimen for Phase 1a participants and by disease type for Phase 1b participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.26 days*µg/mL/mg | Standard Deviation 0.588 |
| Cabiralizumab 4 mg/kg Q2W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.70 days*µg/mL/mg | Standard Deviation 0.444 |
| Cabiralizumab 6 mg/kg Q2W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.84 days*µg/mL/mg | Standard Deviation 0.684 |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 0.66 days*µg/mL/mg | Standard Deviation 0.346 |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.22 days*µg/mL/mg | Standard Deviation 0.97 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.66 days*µg/mL/mg | Standard Deviation 0.737 |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 3.65 days*µg/mL/mg | Standard Deviation 0.696 |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 2.14 days*µg/mL/mg | Standard Deviation 0.509 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.75 days*µg/mL/mg | Standard Deviation 0.982 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Naïve) | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.74 days*µg/mL/mg | Standard Deviation 0.769 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Naïve) | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 2.83 days*µg/mL/mg | Standard Deviation 1.602 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Resistant) | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.46 days*µg/mL/mg | Standard Deviation 0.562 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Resistant) | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 3.52 days*µg/mL/mg | Standard Deviation 1.29 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: SCCHN | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 2.63 days*µg/mL/mg | Standard Deviation 1.128 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: SCCHN | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.42 days*µg/mL/mg | Standard Deviation 0.404 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Pancreatic Cancer | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 2.32 days*µg/mL/mg | Standard Deviation 0.694 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Pancreatic Cancer | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.52 days*µg/mL/mg | Standard Deviation 0.494 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Ovarian Cancer | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 2.69 days*µg/mL/mg | Standard Deviation 1.307 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Ovarian Cancer | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.95 days*µg/mL/mg | Standard Deviation 0.753 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: RCC | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.31 days*µg/mL/mg | Standard Deviation 0.46 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: RCC | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 2.67 days*µg/mL/mg | Standard Deviation 2.12 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: GBM | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 4.69 days*µg/mL/mg | Standard Deviation 2.058 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: GBM | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 2.09 days*µg/mL/mg | Standard Deviation 0.733 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Melanoma | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 1 | 1.48 days*µg/mL/mg | Standard Deviation 0.587 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Melanoma | Pharmacokinetics (PK) of Cabiralizumab: Area Under the Concentration Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-t) Normalized by Dose (Phase 1a and 1b) | Cycle 8 | 4.43 days*µg/mL/mg | Standard Deviation 1.126 |
Secondary
PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin)
Cabiralizumab serum concentration was determined using a validated enzyme-linked immunosorbent assay method. Cmax is the maximum observed serum concentration of cabiralizumab during the dosing period. Cmin is the minimum observed serum concentration of cabiralizumab during a dosing interval (excluding pre-dose concentration before the first dose).
Time frame: Cycles 1 and 8, Day 1 predose, and at 0.25, 4, 24, 72, 168, and 336 hours after the end of infusion.
Population: The PK evaluable population included participants who received at least 1 dose of cabiralizumab, had at least 1 available serum concentration data, and adequate PK assessments which could be used to reliably derive at least 1 PK parameter. Not all participants completed 8 cycles.~PK data are reported by treatment regimen for Phase 1a participants and by disease type for Phase 1b participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cabiralizumab 2 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 2.68 µg/mL | Standard Deviation 2.223 |
| Cabiralizumab 2 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 52.11 µg/mL | Standard Deviation 10.663 |
| Cabiralizumab 4 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 104.82 µg/mL | Standard Deviation 21.543 |
| Cabiralizumab 4 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 28.61 µg/mL | Standard Deviation 17.127 |
| Cabiralizumab 6 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 37.08 µg/mL | Standard Deviation 18.49 |
| Cabiralizumab 6 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 142.83 µg/mL | Standard Deviation 38.528 |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 3.29 µg/mL | Standard Deviation 4.414 |
| Cabiralizumab 1 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 21.93 µg/mL | Standard Deviation 7.651 |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 3.96 µg/mL | Standard Deviation 2.711 |
| Cabiralizumab 2 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 49.00 µg/mL | Standard Deviation 17.314 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 104.47 µg/mL | Standard Deviation 6.89 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 25.57 µg/mL | Standard Deviation 16.098 |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 109.66 µg/mL | Standard Deviation 58.42 |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 187.27 µg/mL | Standard Deviation 63.438 |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 124.36 µg/mL | Standard Deviation 8.825 |
| Cabiralizumab 6 mg/kg + Nivolumab 3 mg/kg Q2W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 28.76 µg/mL | Standard Deviation 5.307 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 85.45 µg/mL | Standard Deviation 16.75 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q3W | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 10.34 µg/mL | Standard Deviation 8.351 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Naïve) | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 38.79 µg/mL | Standard Deviation 20.999 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Naïve) | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 93.41 µg/mL | Standard Deviation 25.708 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Naïve) | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 16.22 µg/mL | Standard Deviation 10.176 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Naïve) | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 126.01 µg/mL | Standard Deviation 39.937 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Resistant) | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 93.69 µg/mL | Standard Deviation 23.406 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Resistant) | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 17.82 µg/mL | Standard Deviation 10.054 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Resistant) | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 142.85 µg/mL | Standard Deviation 44.856 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: NSCLC (PD-1 Resistant) | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 52.26 µg/mL | Standard Deviation 6.642 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: SCCHN | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 37.05 µg/mL | Standard Deviation 13.674 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: SCCHN | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 83.01 µg/mL | Standard Deviation 37.646 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: SCCHN | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 13.65 µg/mL | Standard Deviation 6.959 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: SCCHN | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 97.24 µg/mL | Standard Deviation 25.252 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Pancreatic Cancer | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 81.40 µg/mL | Standard Deviation 17.451 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Pancreatic Cancer | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 15.45 µg/mL | Standard Deviation 9.663 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Pancreatic Cancer | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 40.63 µg/mL | Standard Deviation 11.189 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Pancreatic Cancer | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 108.76 µg/mL | Standard Deviation 24.249 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Ovarian Cancer | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 36.95 µg/mL | Standard Deviation 15.291 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Ovarian Cancer | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 130.17 µg/mL | Standard Deviation 29.845 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Ovarian Cancer | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 25.07 µg/mL | Standard Deviation 12.496 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Ovarian Cancer | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 102.62 µg/mL | Standard Deviation 23.863 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: RCC | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 14.19 µg/mL | Standard Deviation 9.111 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: RCC | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 121.06 µg/mL | Standard Deviation 40.392 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: RCC | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 87.42 µg/mL | Standard Deviation 22.209 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: RCC | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 40.15 µg/mL | Standard Deviation 16.612 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: GBM | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 167.66 µg/mL | Standard Deviation 47.96 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: GBM | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 31.96 µg/mL | Standard Deviation 16.282 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: GBM | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 85.33 µg/mL | Standard Deviation 30.039 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: GBM | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 103.09 µg/mL | Standard Deviation 18.816 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Melanoma | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 8 | 82.00 µg/mL | Standard Deviation 12.572 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Melanoma | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 8 | 164.47 µg/mL | Standard Deviation 15.283 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Melanoma | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmax Cycle 1 | 92.06 µg/mL | Standard Deviation 13.515 |
| Cabiralizumab 4 mg/kg + Nivolumab 3 mg/kg Q2W: Melanoma | PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) | Cmin Cycle 1 | 17.75 µg/mL | Standard Deviation 12.316 |