Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer
Study Details
Study Description
Brief Summary
This is an ongoing Phase 1/2, open-label, multicenter, non-randomized study of MEDI4736 (durvalumab) in subjects with recurrent, platinum-resistant ovarian cancer who are scheduled to receive pegylated liposomal doxorubicin (PLD).The primary objective of Phase 1 is to determine the maximum tolerated dose (MTD) and safety profile, with a secondary objective to evaluate the clinical efficacy as measured by progression-free survival (PFS) rate at 6 months (PFS-6). The primary objective of Phase 2 is the evaluation of clinical efficacy as measured by PFS-6. For both phases, secondary objectives include evaluation of clinical efficacy as measured by overall response rate, PFS, and overall survival (OS), safety and tolerability, and immunological responses.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
In the completed Phase 1 part of the study, eligible subjects were enrolled using a standard 3 + 3 design to identify the MTD (i.e., the highest dose for which fewer than 33% of subjects experienced a dose-limiting toxicity [DLT]) of combination study treatment. All dose levels in Phase 1 included intravenous (IV) PLD (40 mg/m2) in combination with subcutaneous (SC) motolimod (2.0 or 2.5 mg/m2), using a starting dose of 3 mg/kg of IV durvalumab given every 2 weeks (Q2W) or 1500 mg of IV durvalumab given every 4 weeks (Q4W). All subjects in a cohort had their safety data reviewed for DLTs before proceeding with cohort expansion.
After completion of Phase 1 and determination of the durvalumab MTD to be carried forward into Phase 2, availability of data from another study (NCT01666444) indicated a lack of additive efficacy when motolimod was administered with PLD compared with PLD alone. As such, motolimod dosing was discontinued for all subjects in Study LUD2014-001 after completion of Phase 1. Subjects who had initiated treatment may have continued to receive PLD and durvalumab at their respective dose levels but must have discontinued motolimod. Thus, in the fully-accrued but ongoing Phase 2 portion of the study, subjects received only PLD (40 mg/m^2) in combination with durvalumab at the MTD determined in Phase 1 (1500 mg every 4 weeks [Q4W]).
Subjects are treated in the Core Study for an initial 12 cycles (28 days each) according to their treatment assignment. Durvalumab treatment may be extended for subjects who complete the Core Study with stable disease or better and upon agreement among the subject, Sponsor, and Investigator; extended durvalumab monotherapy may continue until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met.
Subjects are followed on study for 90 days after the last drug administration and off study every 3 months for 3 years from the date of the first dose of study treatment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1, Dose Level 0a Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. |
Drug: Durvalumab
Durvalumab is administered as an IV infusion over 60 ± 5 minutes.
Other Names:
Drug: Pegylated Liposomal Doxorubicin
PLD was administered as an IV infusion in accordance with local prescribing information.
Other Names:
Drug: Motolimod
Motolimod was administered as an SC injection. Within 30 minutes prior to each dose of motolimod, subjects were administered 650-1000 mg acetaminophen by mouth to help mitigate potential adverse events (AEs) commonly associated with the administration of motolimod (e.g., fever, myalgia). On days with concurrent motolimod and durvalumab dosing, motolimod administration occurred 30-60 minutes after the end of the durvalumab infusion. After completion of Phase 1, a protocol amendment was implemented to remove motolimod dosing from the study.
Other Names:
|
| Experimental: Phase 1, Dose Level 0b Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. |
Drug: Durvalumab
Durvalumab is administered as an IV infusion over 60 ± 5 minutes.
Other Names:
Drug: Pegylated Liposomal Doxorubicin
PLD was administered as an IV infusion in accordance with local prescribing information.
Other Names:
Drug: Motolimod
Motolimod was administered as an SC injection. Within 30 minutes prior to each dose of motolimod, subjects were administered 650-1000 mg acetaminophen by mouth to help mitigate potential adverse events (AEs) commonly associated with the administration of motolimod (e.g., fever, myalgia). On days with concurrent motolimod and durvalumab dosing, motolimod administration occurred 30-60 minutes after the end of the durvalumab infusion. After completion of Phase 1, a protocol amendment was implemented to remove motolimod dosing from the study.
Other Names:
|
| Experimental: Phase 1, Dose Level +1 Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. |
Drug: Durvalumab
Durvalumab is administered as an IV infusion over 60 ± 5 minutes.
Other Names:
Drug: Pegylated Liposomal Doxorubicin
PLD was administered as an IV infusion in accordance with local prescribing information.
Other Names:
Drug: Motolimod
Motolimod was administered as an SC injection. Within 30 minutes prior to each dose of motolimod, subjects were administered 650-1000 mg acetaminophen by mouth to help mitigate potential adverse events (AEs) commonly associated with the administration of motolimod (e.g., fever, myalgia). On days with concurrent motolimod and durvalumab dosing, motolimod administration occurred 30-60 minutes after the end of the durvalumab infusion. After completion of Phase 1, a protocol amendment was implemented to remove motolimod dosing from the study.
Other Names:
|
| Experimental: Phase 2 Subjects received the MTD determined in Phase 1 (Dose Level +1), comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
Drug: Durvalumab
Durvalumab is administered as an IV infusion over 60 ± 5 minutes.
Other Names:
Drug: Pegylated Liposomal Doxorubicin
PLD was administered as an IV infusion in accordance with local prescribing information.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [Up to 3.05 years]
The primary endpoint in Phase 1 and a secondary endpoint in Phase 2 is the safety/tolerability of study treatment. Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) are reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of study treatment. Treatment-emergent AEs are those that occurred or worsened after administration of the first dose of study treatment.
- Progression-free Survival Rate at 6 Months (PFS-6) by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Estimated Using the Kaplan-Meier Method [Up to 6 months for each subject]
PFS-6 according to RECIST 1.1 is the primary endpoint in Phase 2 and a secondary endpoint in Phase 1, where PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009).
Secondary Outcome Measures
- Number of Subjects With Best Overall Tumor Response by RECIST 1.1 [Up to 36.6 months]
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 14 days before the first dose of study treatment), every 3 cycles during study treatment, and during on-study follow-up approximately 3 months after the last disease assessment. Per RECIST 1.1, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria (Eisenhauer et al 2009).
- Median PFS by RECIST 1.1 as Estimated Using the Kaplan-Meier Method [Up to 36.6 months]
PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to RECIST 1.1 or to the date of death, if disease progression does not occur. Per RECIST 1.1, PD is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009).
- PFS-12 by RECIST 1.1 as Estimated Using the Kaplan-Meier Method [Up to 12 months for each subject]
PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to RECIST 1.1 or to the date of death, if disease progression does not occur. Per RECIST 1.1, PD is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009).
- Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) [Up to 36.6 months]
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 14 days before the first dose of study treatment), every 3 cycles during study treatment, and during on-study follow-up approximately 3 months after the last disease assessment. Per irRECIST, measurable lesions are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria (Bohnsack et al 2014).
- PFS-6 by irRECIST as Estimated Using the Kaplan-Meier Method [Up to 6 months for each subject]
PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB (Bohnsack et al 2014).
- PFS-12 by irRECIST as Estimated Using the Kaplan-Meier Method [Up to 12 months for each subject]
PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB (Bohnsack et al 2014).
- Median PFS by irRECIST as Estimated Using the Kaplan-Meier Method [Up to 36.6 months]
PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB (Bohnsack et al 2014).
- Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method [Up to 36.6 months]
After completion of treatment, all subjects are followed for survival every 3 months for up to 3 years following initiation of study treatment or or for subjects continuing treatment, completion of study treatment whichever was longer. OS is measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up are censored on the date when they were last known to be alive.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Subjects must have had recurrent or persistent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with measurable disease (as defined by the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1.) after first or second line platinum-based chemotherapy, for which treatment with PLD was indicated. Platinum-based therapy was defined as treatment with carboplatin, cisplatin or another organoplatinum compound. Platinum-resistant was defined as having a platinum-free interval of < 12 months after first- or second-line platinum-based chemotherapy, or having disease progression while receiving second-line platinum-based chemotherapy.
Subjects were allowed to have received, but were not required to have received:
-
one additional cytotoxic regimen and/or poly adenosine diphosphate-ribose polymerase inhibitor for management of recurrent or persistent disease.
-
biologic therapy (e.g., bevacizumab) as part of their primary treatment regimen or part of their treatment for management of recurrent or persistent disease.
-
Histologic documentation of the original primary tumor.
-
Documented radiographic disease progression < 12 months after the last dose of first- or second-line platinum-based chemotherapy.
-
Subjects in Phase 2 must have had disease amenable to biopsy and must have been willing to undergo pre- and post-treatment tumor biopsies. Optional for Phase 1.
Note: archival tissue was requested for all subjects preferably from primary tumor site prior to cancer treatment; however, archival tissue was not a requirement for study entry.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
-
Laboratory parameters for vital functions should have been in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which must have been within the ranges specified, regardless of clinical significance:
-
Hemoglobin: ≥ 9 g/dL
-
Neutrophil count: ≥ 1.5 x 10^9/L
-
Platelet count: ≥ 100,000/mm^3
-
Serum creatinine: ≤ 1.5 x institutional upper limit of normal (ULN), or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula)
-
Serum bilirubin: ≤ 1.2 mg/dL
-
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): ≤ 2.5 x ULN
-
Alkaline phosphatase: ≤ 2.5 x ULN
-
Age ≥18 years.
-
Able and willing to give valid written informed consent.
-
Body weight > 30 kg.
Exclusion Criteria:
-
Prior exposure to doxorubicin, PLD or any other anthracycline, motolimod and other toll-like receptor agonists, durvalumab or checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1)/anti-programmed cell death ligand-1 (PD-L1) antibodies.
-
Subjects with platinum-refractory disease, defined as disease progression while receiving first line platinum-based therapy.
-
Clinically significant persistent immune-related adverse events following prior therapy.
-
Subjects with history or evidence upon physical examination of central nervous system disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or, within 6 months prior to Day 1 of this study, history of cerebrovascular accident (stroke), transient ischemic attack or subarachnoid hemorrhage.
-
Subjects with clinically significant cardiovascular disease. This included:
-
Resistant hypertension.
-
Myocardial infarction or unstable angina within 6 months prior to Day 1 of the study.
-
History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled with anti-arrhythmic medication.
-
Baseline ejection fraction ≤ 50% as assessed by echocardiogram or multiple-gated acquisition.
-
New York Heart Association Class II or higher congestive heart failure.
-
Grade 2 or higher peripheral ischemia, except for brief (< 24 hours) episodes of ischemia managed non-surgically and without permanent deficit.
-
History of pneumonitis or interstitial lung disease.
-
Active, suspected or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegner's granulomatosis, active Hashimoto's thyroiditis, rheumatoid arthritis, lupus, scleroderma and its variants, multiple sclerosis, myasthenia gravis). Vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger were permitted.
-
Other malignancy within 2 years prior to Day 1 of the study, except for those treated with surgical intervention only.
-
Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who required drainage gastrostomy tube and/or parenteral hydration or nutrition.
-
Known immunodeficiency or human immunodeficiency virus, Hepatitis B or Hepatitis C positivity.
-
History of severe allergic reactions to any unknown allergens or components of the study drugs.
-
Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
-
Prior treatment in any other interventional clinical trial within 4 weeks prior to Day 1 of the study.
-
Mental impairment that may have compromised compliance with the requirements of the study.
-
Lack of availability for immunological and clinical follow-up assessment.
-
Women of childbearing potential who were found to be pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) or nursing. NOTE: Pregnancy tests were not required for subjects who were not of childbearing potential as defined in #17.
-
Female subjects of childbearing potential who were sexually active with a nonsterilized male partner must have used at least one highly effective method of contraception from screening, and must have agreed to continue using such precautions for 90 days after the final dose of investigational product (durvalumab). Male partners of a female subject must have used male condom plus spermicide throughout this period (from screening and for 90 days after subject's receipt of the final dose of investigational product). Cessation of birth control after this point should have been discussed with a responsible physician. Not engaging in sexual activity for the total duration of the trial and the drug washout period was an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method were not acceptable methods of birth control.
Female subjects should have refrained from breastfeeding throughout the period described above.
NOTE: For the standard of care, PLD (Doxil®, Caelyx®), the package insert advises females of reproductive potential to use effective contraception during and for 6 months after last treatment with the drug. Therefore, all subjects of childbearing potential on this study should have continued contraception use for 6 months after the last PLD administration.
Females of childbearing potential were defined as those who were not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or post-menopausal.
Females were considered post-menopausal if they had been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements applied:
-
Females < 50 years of age were considered post-menopausal if they had been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they had luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
-
Females ≥ 50 years of age were considered post-menopausal if they had been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
A highly effective method of contraception was defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Note that some contraception methods were not considered highly effective (e.g., male or female condom with or without spermicide; female cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action [excluding Cerazette/desogestrel which is considered highly effective]; and triphasic combined oral contraceptive pills).
-
Any condition that, in the clinical judgment of the treating physician, was likely to prevent the subject from complying with any aspect of the protocol or that may have put the subject at unacceptable risk.
-
Subjects must not have donated blood while on study and for at least 90 days following the last durvalumab treatment.
-
History of allogeneic organ transplant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Facitlity | Phoenix | Arizona | United States | 85016 |
| 2 | Research Facility | New York | New York | United States | 10065 |
| 3 | Research Facility | Hilliard | Ohio | United States | 43026 |
| 4 | Research Facility | Providence | Rhode Island | United States | 02905 |
| 5 | Research Facility | Lausanne | Switzerland | 1011 |
Sponsors and Collaborators
- Ludwig Institute for Cancer Research
- MedImmune LLC
- Celgene
- Cancer Research Institute, New York City
Investigators
- Study Chair: George Coukos, MD, PhD, University of Lausanne Hospitals
- Study Chair: Bradley J Monk, MD, Arizona Oncology
Study Documents (Full-Text)
More Information
Publications
- Bohnsack O, Hoos A, Ludajic K. Adaptation of the immune related response criteria: irRECIST. Ann Oncol. 2014 Sep;25(suppl 4):iv361-iv72 [Abstract 4958]. doi: 10.1093/annonc/mdu342.23.
- Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- LUD2014-001
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received pegylated liposomal doxorubicin (PLD) (40 mg/m^2 intravenously [IV] on Day 1 of every cycle) + durvalumab (3 mg/kg every 2 weeks [Q2W, equivalent to 450 mg every 4 weeks (Q4W)] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 subcutaneous [SC]) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the maximum tolerated dose (MTD) determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Period Title: Overall Study | ||||
| STARTED | 3 | 4 | 6 | 40 |
| COMPLETED | 1 | 1 | 2 | 9 |
| NOT COMPLETED | 2 | 3 | 4 | 31 |
Baseline Characteristics
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. | Total of all reporting groups |
| Overall Participants | 3 | 4 | 6 | 40 | 53 |
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
60.0
|
55.0
|
62.5
|
65.0
|
64.0
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
100%
|
4
100%
|
6
100%
|
40
100%
|
53
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
5
12.5%
|
5
9.4%
|
| Not Hispanic or Latino |
3
100%
|
4
100%
|
6
100%
|
33
82.5%
|
46
86.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
2
5%
|
2
3.8%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
25%
|
1
16.7%
|
0
0%
|
2
3.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
1
16.7%
|
1
2.5%
|
2
3.8%
|
| White |
3
100%
|
3
75%
|
4
66.7%
|
35
87.5%
|
45
84.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
4
10%
|
4
7.5%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
3
100%
|
3
75%
|
4
66.7%
|
27
67.5%
|
37
69.8%
|
| Switzerland |
0
0%
|
1
25%
|
2
33.3%
|
13
32.5%
|
16
30.2%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline (Count of Participants) | |||||
| 0 |
3
100%
|
2
50%
|
5
83.3%
|
34
85%
|
44
83%
|
| 1 |
0
0%
|
2
50%
|
1
16.7%
|
6
15%
|
9
17%
|
Outcome Measures
| Title | Number of Subjects With Treatment-emergent Adverse Events (TEAEs) |
|---|---|
| Description | The primary endpoint in Phase 1 and a secondary endpoint in Phase 2 is the safety/tolerability of study treatment. Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) are reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 90 days after the last dose of study treatment. Treatment-emergent AEs are those that occurred or worsened after administration of the first dose of study treatment. |
| Time Frame | Up to 3.05 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| Any TEAE |
3
100%
|
4
100%
|
6
100%
|
40
100%
|
| TEAE related to any study treatment |
3
100%
|
4
100%
|
6
100%
|
38
95%
|
| TEAE related to durvalumab |
2
66.7%
|
4
100%
|
5
83.3%
|
32
80%
|
| TEAE related to PLD |
3
100%
|
4
100%
|
5
83.3%
|
37
92.5%
|
| TEAE related to motolimod |
3
100%
|
4
100%
|
6
100%
|
1
2.5%
|
| Serious TEAE |
0
0%
|
2
50%
|
1
16.7%
|
23
57.5%
|
| Title | Progression-free Survival Rate at 6 Months (PFS-6) by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Estimated Using the Kaplan-Meier Method |
|---|---|
| Description | PFS-6 according to RECIST 1.1 is the primary endpoint in Phase 2 and a secondary endpoint in Phase 1, where PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009). |
| Time Frame | Up to 6 months for each subject |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| Number (95% Confidence Interval) [percentage of participants] |
33.3
1110%
|
50.0
1250%
|
33.3
555%
|
42.9
107.3%
|
| Title | Number of Subjects With Best Overall Tumor Response by RECIST 1.1 |
|---|---|
| Description | Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 14 days before the first dose of study treatment), every 3 cycles during study treatment, and during on-study follow-up approximately 3 months after the last disease assessment. Per RECIST 1.1, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria (Eisenhauer et al 2009). |
| Time Frame | Up to 36.6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| CR |
0
0%
|
0
0%
|
0
0%
|
4
10%
|
| PR |
1
33.3%
|
1
25%
|
2
33.3%
|
5
12.5%
|
| SD |
1
33.3%
|
1
25%
|
1
16.7%
|
15
37.5%
|
| PD |
1
33.3%
|
2
50%
|
3
50%
|
16
40%
|
| Title | Median PFS by RECIST 1.1 as Estimated Using the Kaplan-Meier Method |
|---|---|
| Description | PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to RECIST 1.1 or to the date of death, if disease progression does not occur. Per RECIST 1.1, PD is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009). |
| Time Frame | Up to 36.6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| Median (95% Confidence Interval) [months] |
5.6
|
5.7
|
4.3
|
5.5
|
| Title | PFS-12 by RECIST 1.1 as Estimated Using the Kaplan-Meier Method |
|---|---|
| Description | PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to RECIST 1.1 or to the date of death, if disease progression does not occur. Per RECIST 1.1, PD is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions (Eisenhauer et al 2009). |
| Time Frame | Up to 12 months for each subject |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| Number (95% Confidence Interval) [percentage of participants] |
33.3
1110%
|
25.0
625%
|
16.7
278.3%
|
29.5
73.8%
|
| Title | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) |
|---|---|
| Description | Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 14 days before the first dose of study treatment), every 3 cycles during study treatment, and during on-study follow-up approximately 3 months after the last disease assessment. Per irRECIST, measurable lesions are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria (Bohnsack et al 2014). |
| Time Frame | Up to 36.6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| irCR |
0
0%
|
0
0%
|
0
0%
|
4
10%
|
| irPR |
1
33.3%
|
1
25%
|
2
33.3%
|
6
15%
|
| irSD |
1
33.3%
|
1
25%
|
1
16.7%
|
16
40%
|
| irPD |
1
33.3%
|
2
50%
|
3
50%
|
14
35%
|
| Title | PFS-6 by irRECIST as Estimated Using the Kaplan-Meier Method |
|---|---|
| Description | PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB (Bohnsack et al 2014). |
| Time Frame | Up to 6 months for each subject |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| Number (95% Confidence Interval) [percent of participants] |
33.3
1110%
|
50.0
1250%
|
33.3
555%
|
42.6
106.5%
|
| Title | PFS-12 by irRECIST as Estimated Using the Kaplan-Meier Method |
|---|---|
| Description | PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB (Bohnsack et al 2014). |
| Time Frame | Up to 12 months for each subject |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| Number (95% Confidence Interval) [percent of participants] |
33.3
1110%
|
25.0
625%
|
16.7
278.3%
|
33.4
83.5%
|
| Title | Median PFS by irRECIST as Estimated Using the Kaplan-Meier Method |
|---|---|
| Description | PFS is measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB (Bohnsack et al 2014). |
| Time Frame | Up to 36.6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| Median (95% Confidence Interval) [months] |
5.6
|
5.7
|
4.3
|
5.5
|
| Title | Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method |
|---|---|
| Description | After completion of treatment, all subjects are followed for survival every 3 months for up to 3 years following initiation of study treatment or or for subjects continuing treatment, completion of study treatment whichever was longer. OS is measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up are censored on the date when they were last known to be alive. |
| Time Frame | Up to 36.6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The population comprises all subjects who received at least one dose of study treatment. |
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. |
| Measure Participants | 3 | 4 | 6 | 40 |
| Median (95% Confidence Interval) [months] |
27.7
|
NA
|
12.8
|
17.6
|
Adverse Events
| Time Frame | All AEs occurring between the signing of informed consent and the off-study date (i.e., through 90 days after the last dose of study treatment [up to 3.05 years]) are documented, regardless of the causal relationship to study drug. AEs that occur or worsen in severity after the first dose of study treatment are considered treatment emergent (i.e., TEAEs). | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AE documentation includes onset/resolution dates, severity using the NCI CTCAE (version 4.03), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, preferred terms are counted only once per subject at the maximum reported grade. | |||||||
| Arm/Group Title | Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 | ||||
| Arm/Group Description | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (3 mg/kg Q2W [equivalent to 450 mg Q4W] IV on Days 3 and 17 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Days 3 and 17 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.0 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. Prior to removal of motolimod from the study, subjects received motolimod (2.5 mg/m^2 SC) on Days 3, 10, and 17 of Cycles 1-3 and Day 3 of Cycles 4-12. | Subjects received the MTD determined in Phase 1, comprising PLD (40 mg/m^2 IV on Day 1 of every cycle) + durvalumab (1500 mg Q4W IV on Day 3 of every cycle) for up to 12 continuous 28-day cycles (Core Study), with extended durvalumab monotherapy permitted for subjects tolerating and benefiting from treatment. | ||||
All Cause Mortality |
||||||||
| Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 2/4 (50%) | 4/6 (66.7%) | 21/40 (52.5%) | ||||
Serious Adverse Events |
||||||||
| Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 2/4 (50%) | 1/6 (16.7%) | 23/40 (57.5%) | ||||
| Eye disorders | ||||||||
| Vision blurred | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Ascites | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Diarrhoea | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Ileus | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 2/40 (5%) | ||||
| Rectal obstruction | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Small intestinal obstruction | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Stomatitis | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 2/40 (5%) | ||||
| Subileus | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| General disorders | ||||||||
| General physical health deterioration | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Pyrexia | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholelithiasis | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Bacterial translocation | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Lung infection | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Sepsis | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Fracture | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Hip fracture | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Infusion related reaction | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Wound dehiscence | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Wound complication | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Investigations | ||||||||
| Nutritional condition abnormal | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypercalcaemia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Muscular weakness | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Malignant neoplasm progression | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Nervous system disorders | ||||||||
| Aphasia | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Transient ischaemic attack | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Radiculitis | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Renal and urinary disorders | ||||||||
| Urinary tract obstruction | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bronchial obstruction | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Pleural effusion | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Pleural fibrosis | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis bullous | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Surgical and medical procedures | ||||||||
| Lymphadenectomy | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Tumour excision | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Phase 1, Dose Level 0a | Phase 1, Dose Level 0b | Phase 1, Dose Level +1 | Phase 2 | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 4/4 (100%) | 6/6 (100%) | 40/40 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 7/40 (17.5%) | ||||
| Cardiac disorders | ||||||||
| Palpitations | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Pericardial effusion | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Sinus bradycardia | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Sinus tachycardia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| Endocrine disorders | ||||||||
| Hyperthyroidism | 2/3 (66.7%) | 0/4 (0%) | 1/6 (16.7%) | 4/40 (10%) | ||||
| Hypothyroidism | 1/3 (33.3%) | 2/4 (50%) | 2/6 (33.3%) | 3/40 (7.5%) | ||||
| Eye disorders | ||||||||
| Conjunctival ulcer | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Dry eye | 1/3 (33.3%) | 2/4 (50%) | 0/6 (0%) | 0/40 (0%) | ||||
| Eye pain | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 2/40 (5%) | ||||
| Abdominal pain | 0/3 (0%) | 2/4 (50%) | 2/6 (33.3%) | 9/40 (22.5%) | ||||
| Abdominal pain upper | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 8/40 (20%) | ||||
| Anal fissure | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/40 (0%) | ||||
| Anal haemorrhage | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Constipation | 1/3 (33.3%) | 2/4 (50%) | 2/6 (33.3%) | 11/40 (27.5%) | ||||
| Diarrhoea | 1/3 (33.3%) | 1/4 (25%) | 2/6 (33.3%) | 10/40 (25%) | ||||
| Dry mouth | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Dyspepsia | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Dysphagia | 0/3 (0%) | 1/4 (25%) | 2/6 (33.3%) | 3/40 (7.5%) | ||||
| Gastrointestinal pain | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Gastrooesophageal reflux disease | 0/3 (0%) | 0/4 (0%) | 2/6 (33.3%) | 5/40 (12.5%) | ||||
| Haemorrhoids | 1/3 (33.3%) | 1/4 (25%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Nausea | 1/3 (33.3%) | 4/4 (100%) | 3/6 (50%) | 19/40 (47.5%) | ||||
| Oral pain | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Rectal haemorrhage | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Stomatitis | 2/3 (66.7%) | 2/4 (50%) | 4/6 (66.7%) | 18/40 (45%) | ||||
| Vomiting | 0/3 (0%) | 3/4 (75%) | 3/6 (50%) | 11/40 (27.5%) | ||||
| Abdominal pain lower | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| General disorders | ||||||||
| Catheter site pain | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Chest discomfort | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Chills | 2/3 (66.7%) | 2/4 (50%) | 6/6 (100%) | 4/40 (10%) | ||||
| Fatigue | 3/3 (100%) | 3/4 (75%) | 4/6 (66.7%) | 21/40 (52.5%) | ||||
| Feeling cold | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Influenza like illness | 3/3 (100%) | 1/4 (25%) | 0/6 (0%) | 2/40 (5%) | ||||
| Injection site discolouration | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Injection site erythema | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Injection site pain | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Injection site reaction | 3/3 (100%) | 3/4 (75%) | 5/6 (83.3%) | 0/40 (0%) | ||||
| Injection site vesicles | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Non-cardiac chest pain | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Oedema peripheral | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Pain | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Pyrexia | 2/3 (66.7%) | 2/4 (50%) | 5/6 (83.3%) | 10/40 (25%) | ||||
| Sensation of foreign body | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Catheter site rash | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Malaise | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Cystitis | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Folliculitis | 1/3 (33.3%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Influenza | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Mucosal infection | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 4/40 (10%) | ||||
| Oral candidiasis | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Otitis media | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Pneumonia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 2/40 (5%) | ||||
| Pyelonephritis | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Respiratory tract infection | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 2/40 (5%) | ||||
| Skin infection | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Upper respiratory tract infection | 1/3 (33.3%) | 1/4 (25%) | 0/6 (0%) | 2/40 (5%) | ||||
| Urinary tract infection | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Viral skin infection | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Vulvovaginal candidiasis | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Nasopharyngitis | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Infusion related reaction | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Meniscus injury | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Post procedural haematoma | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Procedural pain | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 5/40 (12.5%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Amylase increased | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 7/40 (17.5%) | ||||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/40 (5%) | ||||
| Blood creatinine increased | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Blood folate decreased | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| C-reactive protein increased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 5/40 (12.5%) | ||||
| Gamma-glutamyltransferase increased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| Lipase increased | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 6/40 (15%) | ||||
| Lymphocyte count decreased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 10/40 (25%) | ||||
| Neutrophil count decreased | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/40 (5%) | ||||
| Platelet count decreased | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Weight decreased | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 6/40 (15%) | ||||
| Weight increased | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| White blood cell count decreased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/3 (0%) | 3/4 (75%) | 1/6 (16.7%) | 9/40 (22.5%) | ||||
| Hypoalbuminaemia | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Hypokalaemia | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 6/40 (15%) | ||||
| Hypomagnesaemia | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 7/40 (17.5%) | ||||
| Hyponatraemia | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 5/40 (12.5%) | ||||
| Hypophosphataemia | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Vitamin B12 deficiency | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Hyperglycemia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Vitamin D deficiency | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/3 (33.3%) | 2/4 (50%) | 1/6 (16.7%) | 2/40 (5%) | ||||
| Back pain | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 8/40 (20%) | ||||
| Groin pain | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/40 (0%) | ||||
| Muscle spasms | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Myalgia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| Neck pain | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Pain in extremity | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Muscular weakness | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Nervous system disorders | ||||||||
| Dysgeusia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Dysphonia psychogenic | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Headache | 2/3 (66.7%) | 2/4 (50%) | 1/6 (16.7%) | 4/40 (10%) | ||||
| Peripheral sensory neuropathy | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Sciatica | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Memory impairment | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/3 (0%) | 2/4 (50%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Confusional state | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Depression | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Insomnia | 0/3 (0%) | 2/4 (50%) | 0/6 (0%) | 7/40 (17.5%) | ||||
| Renal and urinary disorders | ||||||||
| Dysuria | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| Pollakiuria | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| Renal colic | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Renal failure acute | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Urinary incontinence | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Urinary tract pain | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Reproductive system and breast disorders | ||||||||
| Vaginal discharge | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 1/3 (33.3%) | 1/4 (25%) | 2/6 (33.3%) | 11/40 (27.5%) | ||||
| Dysphonia | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Dyspnoea | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 8/40 (20%) | ||||
| Epistaxis | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/40 (2.5%) | ||||
| Laryngeal inflammation | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/40 (0%) | ||||
| Nasal congestion | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 5/40 (12.5%) | ||||
| Oropharyngeal pain | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 2/40 (5%) | ||||
| Pleural effusion | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Pneumonitis | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 3/40 (7.5%) | ||||
| Productive cough | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Rhinorrhoea | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Throat irritation | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 1/3 (33.3%) | 1/4 (25%) | 1/6 (16.7%) | 5/40 (12.5%) | ||||
| Dermatitis acneiform | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| Dry skin | 2/3 (66.7%) | 2/4 (50%) | 1/6 (16.7%) | 4/40 (10%) | ||||
| Erythema | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Hyperkeratosis | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Night sweats | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 2/3 (66.7%) | 1/4 (25%) | 3/6 (50%) | 23/40 (57.5%) | ||||
| Photosensitivity reaction | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/40 (5%) | ||||
| Pruritus | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 11/40 (27.5%) | ||||
| Rash | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 6/40 (15%) | ||||
| Rash maculo-papular | 3/3 (100%) | 2/4 (50%) | 2/6 (33.3%) | 19/40 (47.5%) | ||||
| Skin exfoliation | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Skin hyperpigmentation | 0/3 (0%) | 1/4 (25%) | 3/6 (50%) | 2/40 (5%) | ||||
| Skin induration | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/40 (0%) | ||||
| Urticaria | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/40 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/40 (2.5%) | ||||
| Embolism | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 2/40 (5%) | ||||
| Haematoma | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/40 (0%) | ||||
| Hypertension | 1/3 (33.3%) | 1/4 (25%) | 0/6 (0%) | 4/40 (10%) | ||||
| Hypotension | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 3/40 (7.5%) | ||||
| Lymphoedema | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/40 (2.5%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Mary Macri, Director, Clinical Trials Management |
|---|---|
| Organization | Ludwig Institute for Cancer Research |
| Phone | (212) 450-1546 |
| mmacri@lcr.org |
- LUD2014-001