Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2022
• Main ID: NCT02431559
• Date of registration: 27/04/2015
• Prospective Registration: Yes
• Primary sponsor: Ludwig Institute for Cancer Research
• Public title: Phase 1/2 Study of Motolimod, Doxorubicin, and Durvalumab in Recurrent, Platinum-Resistant Ovarian Cancer
• Scientific title: Phase 1/2 Study of Chemoimmunotherapy With Toll-like Receptor 8 Agonist Motolimod (VTX-2337) + Anti-PD-L1 Antibody MEDI4736 in Subjects With Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin is Indicated
• Date of first enrolment: December 2, 2015
• Target sample size: 53
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02431559
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Switzerland, United States

Contacts

• Name: Bradley J Monk, MD
• Affiliation: Arizona Oncology

• Name: George Coukos, MD, PhD
• Affiliation: University of Lausanne Hospitals

Key inclusion & exclusion criteria

Inclusion Criteria:

1. 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.

2. Histologic documentation of the original primary tumor.

3. Documented radiographic disease progression < 12 months after the last dose of first-
or second-line platinum-based chemotherapy.

4. 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.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. 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

7. Age =18 years.

8. Able and willing to give valid written informed consent.

9. Body weight > 30 kg.

Exclusion Criteria:

1. 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.

2. Subjects with platinum-refractory disease, defined as disease progression while
receiving first line platinum-based therapy.

3. Clinically significant persistent immune-related adverse events following prior
therapy.

4. 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.

5. Subjects with clinically significant cardiovascular disease. This included:

1. Resistant hypertension.

2. Myocardial infarction or unstable angina within 6 months prior to Day 1 of the
study.

3. 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.

4. Baseline ejection fraction = 50% as assessed by echocardiogram or multiple-gated
acquisition.

5. New York Heart Association Class II or higher congestive heart failure.

6. Grade 2 or higher peripheral ischemia, except for brief (< 24 hours) episodes of
ischemia managed non-surgically and without permanent deficit.

6. History of pneumonitis or interstitial lung disease.

7. 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.

8. Other malignancy within 2 years prior to Day 1 of the study, except for those treated
with surgical intervention only.

9. Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who
required drainage gastrostomy tube and/or parenteral hydration or nutrition.

10. Known immunodeficiency or human immunodeficiency virus, Hepatitis B or Hepatitis C
positivity.

11. History of severe allergic reactions to any unknown allergens or components of the
study drugs.

12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
disorders).

13. Prior treatment in any other interventional clinical trial within 4 weeks prior to Day
1 of the study.

14. Mental impairment that may have compromised compliance with the requirements of the
study.

15. Lack of availability for immunological and clinical follow-up assessment.

16. 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.

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



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Ovarian Cancer

Intervention(s)

Drug: Motolimod

Drug: Durvalumab

Drug: Pegylated Liposomal Doxorubicin

Primary Outcome(s)

Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [Time Frame: Up to 3.05 years]

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 [Time Frame: Up to 6 months for each subject]

Secondary Outcome(s)

Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) [Time Frame: Up to 36.6 months]

PFS-12 by irRECIST as Estimated Using the Kaplan-Meier Method [Time Frame: Up to 12 months for each subject]

Median PFS by RECIST 1.1 as Estimated Using the Kaplan-Meier Method [Time Frame: Up to 36.6 months]

PFS-6 by irRECIST as Estimated Using the Kaplan-Meier Method [Time Frame: Up to 6 months for each subject]

Number of Subjects With Best Overall Tumor Response by RECIST 1.1 [Time Frame: Up to 36.6 months]

PFS-12 by RECIST 1.1 as Estimated Using the Kaplan-Meier Method [Time Frame: Up to 12 months for each subject]

Median PFS by irRECIST as Estimated Using the Kaplan-Meier Method [Time Frame: Up to 36.6 months]

Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method [Time Frame: Up to 36.6 months]

Secondary ID(s)

LUD2014-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

MedImmune LLC

Cancer Research Institute, New York City

Celgene

Results

• Results available: Yes
• Date Posted: 23/09/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02431559