Advanced Solid TumorsPhase 1FPA008-003NCT02526017
Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
A Phase 1 study testing Cabiralizumab and Nivolumab in people with Advanced Solid Tumors and Head and Neck Cancer, run by Five Prime Therapeutics, Inc. at 39 sites in United States.
Trial summary
Phase 1a/1b does-escalation study of cabiralizumab alone and with nivolumab in advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Head and Neck Cancer, Pancreatic Cancer
- What is being tested?
- Cabiralizumab and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 313 participants
- Where
- 39 sitesUnited States
- Study dates
- 8 Sep 2015to 18 Nov 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
39 sites in 1 country.
39 sites in 1 country
United States39 sites
Emory University Hospital
Atlanta, Georgia, 30322
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
Hollings Cancer Center, Medical University of South Carolina
Charleston, South Carolina, 29425
Rush University Medical Center
Chicago, Illinois, 60612
University of Chicago Medical Center
Chicago, Illinois, 60637
The Christ Hospital
Cincinnati, Ohio, 45219
Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center
Dallas, Texas, 75246
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Mischer Neuroscience Associates, The University of Texas Health Science Center at Houston
Houston, Texas, 77030
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University Health Hospital
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Moores UC San Diego Cancer Center
La Jolla, California, 92093
Norris Comprehensive Cancer Center, University of Southern California
Los Angeles, California, 90033
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Center
Los Angeles, California, 90048
Norton Cancer Institute, Norton Healthcare Pavilion
Louisville, Kentucky, 40202
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140
Allina Health, Virginia Piper Cancer Institute
Minneapolis, Minnesota, 55407
Henry-Joyce Cancer Clinic, Vanderbilt-Ingram Cancer Center,
Nashville, Tennessee, 37232
Memorial Sloan Kettering
New York, New York, 10065
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
University of Pittsburgh Cancer Institute, William M. Cooper Ambulatory Pavilion of the Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Providence Portland Medical Center
Portland, Oregon, 97213
Oregon Health and Science University
Portland, Oregon, 97239
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229
University of California, San Francisco
San Francisco, California, 94143
Sarcoma Oncology Research Center
Santa Monica, California, 90403
UCLA Hematology/Oncology- Santa Monica
Santa Monica, California, 90404
Scottsdale Healthcare Hospitals DBA Honor Health
Scottsdale, Arizona, 85258
Seattle Cancer Care Alliance
Seattle, Washington, 98109
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase 1a/1b Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
Phase 1a/1b does-escalation study of cabiralizumab alone and with nivolumab in advanced solid tumors.
Read the 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.
- Conditions
- Advanced Solid Tumors, Head and Neck Cancer, Pancreatic Cancer, Ovarian Cancer, Renal Cell Carcinoma, Malignant Glioma
- Being tested
- Cabiralizumab, Nivolumab
- Medical subject headings
- Head and Neck Neoplasms, Pancreatic Neoplasms, Ovarian Neoplasms, Carcinoma, Renal Cell, Glioma, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabiralizumabBiological
Also called Anti-colony stimulating factor-1 receptor (Anti-CSF-1R), FPA008
Solution for IV administration
NivolumabBiological
Also called OPDIVO®, MDX-1106, BMS-936558
Solution for IV administration
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation | Experimental | Cabiralizumab administered at 2 mg/kg every 2 weeks (Q2W), 4 mg/kg Q2W and 6 mg/kg Q2W in participants with any solid tumor. Receives: Biological: Cabiralizumab |
| Phase 1a Combination Therapy Dose Escalation | Experimental | Nivolumab 3 mg/kg Q2W + cabiralizumab at the following doses: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 6 mg/kg Q2W. Also nivolumab 3 mg/kg + cabiralizumab 4 mg/kg every 3 weeks (Q3W). Participants with any solid tumor. Receives: Biological: Cabiralizumab; Biological: Nivolumab |
| Phase 1b Combination Therapy Dose Expansion | Experimental | The expansion phase would use the recommended dose determined in Phase 1a: cabiralizumab 4 mg/kg + nivolumab 3 mg/kg Q2W. Participants are enrolled for the following advanced cancer types: non-small cell lung cancer (anti-programmed cell death 1 [PD1] targeted drug naïve), non-small cell lung cancer (prior treatment with anti-PD-1), pancreatic cancer, ovarian cancer, renal cell cancer, glioblastoma, and melanoma. Receives: Biological: Cabiralizumab; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
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.
Measured: 28 days
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
Secondary outcomes (9)
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.
Measured: From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months.
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.
Measured: 52 weeks
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.
Measured: From first dose of study drug up to the end of study; maximum time on study in Phase 1b was 35.9 months.
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.
Measured: From first dose of study drug up to the end of study; maximum time on study in phase 1b was 35.9 months.
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.
Measured: 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.
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.
Measured: Cycles 1 and 8, Day 1 predose, and at 0.25, 4, 24, 72, 168, and 336 hours after the end of infusion.
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).
Measured: Cycles 1 and 8, Day 1 predose, and at 0.25, 4, 24, 72, 168, and 336 hours after the end of infusion.
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.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2015 (estimated)
- Study start8 Sep 2015
- Primary completion18 Nov 2019
- Study completion18 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 313 participants (actual)
Sponsor and investigators
- Lead sponsor
- Five Prime Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Medical Lead, Study director, Five Prime Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02526017
- Sponsor's protocol ID
- FPA008-003
- Acronym
- FPA008-003
- Status last verified
- Jan 2022
- First submitted
- 13 Aug 2015
- Last updated
- 9 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1a/1b Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
- ClinicalTrials.gov ID
- NCT02526017
- Acronym / sponsor ID
- FPA008-003 / FPA008-003
- Conditions
- Advanced Solid Tumors, Head and Neck Cancer, Pancreatic Cancer, Ovarian Cancer, Renal Cell Carcinoma, Malignant Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 313 participants (actual)
- Lead sponsor
- Five Prime Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 8 Sep 2015 (actual)
- Primary completion
- 18 Nov 2019 (actual)
- Study completion
- 18 Nov 2019 (actual)
- First posted
- 18 Aug 2015 (estimated)
- Results
- Posted 9 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation | Experimental | Biological: CabiralizumabCabiralizumab administered at 2 mg/kg every 2 weeks (Q2W), 4 mg/kg Q2W and 6 mg/kg Q2W in participants with any solid tumor. |
| Phase 1a Combination Therapy Dose Escalation | Experimental | Biological: Cabiralizumab, Biological: NivolumabNivolumab 3 mg/kg Q2W + cabiralizumab at the following doses: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 6 mg/kg Q2W. Also nivolumab 3 mg/kg + cabiralizumab 4 mg/kg every 3 weeks (Q3W). Participants with any solid tumor. |
| Phase 1b Combination Therapy Dose Expansion | Experimental | Biological: Cabiralizumab, Biological: NivolumabThe expansion phase would use the recommended dose determined in Phase 1a: cabiralizumab 4 mg/kg + nivolumab 3 mg/kg Q2W. Participants are enrolled for the following advanced cancer types: non-small cell lung cancer (anti-programmed cell death 1 [PD1] targeted drug naïve), non-small cell lung cancer (prior treatment with anti-PD-1), pancreatic cancer, ovarian cancer, renal cell cancer, glioblastoma, and melanoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabiralizumabAlso: Anti-colony stimulating factor-1 receptor (Anti-CSF-1R), FPA008Solution for IV administration | Biological | Phase 1a Combination Therapy Dose Escalation, Phase 1a Monotherapy Dose Escalation, Phase 1b Combination Therapy Dose Expansion |
| NivolumabAlso: OPDIVO®, MDX-1106, BMS-936558Solution for IV administration | Biological | Phase 1a Combination Therapy Dose Escalation, Phase 1b Combination Therapy Dose Expansion |
Primary outcome
Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a)
Time frame: 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)
Time frame: 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)
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.
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)
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.
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)
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.
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.
9 secondary outcomes
Efficacy: Overall Survival (Phase 1b)
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.
Efficacy: Overall Survival (OS) at One Year (Phase 1b)
Time frame: 52 weeks
Efficacy: Duration of Response (Phase 1b)
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.
Efficacy: Progression Free Survival (Phase 1b)
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.
Efficacy: Objective Response Rate - Central Review Assessment (Phase 1b)
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.
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)
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.
PK of Cabiralizumab: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin)
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.
Immunogenicity of Cabiralizumab: Number of Participants With Anti-Cabiralizumab Antibodies (Phase 1a and 1b)
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
Immunogenicity of Nivolumab: Number of Participants With Anti-Nivolumab Antibodies (Phase 1a and 1b)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Lead study director
Five Prime Therapeutics, Inc.
39 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cabiralizumab and Nivolumab in people with Advanced Solid Tumors and Head and Neck Cancer, run by Five Prime Therapeutics, Inc. at 39 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a) (time frame: 28 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2022.