Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumor, Including a Cohort Expansion in Esophageal Cancer.
NCT ID: NCT03983954
Last Updated: 2025-11-28
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1
120 participants
INTERVENTIONAL
2019-10-10
2027-03-01
Brief Summary
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Detailed Description
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Following the Dose Escalation part, antibodies binding to NAP have been shown to interfere with drug exposure, which makes it unlikely that patients could effectively receive more than 3 cycles of NAP. Obinutuzumab pretreatment was added to the combination of durvalumab and NAP given at the 2 highest safe dose levels of the combination of durvalumab and NAP in the dose-escalation part of this Phase 1b study (3 patients per dose level), and to the MTD expansion part that included several cohorts.
The combination of NAP/durvalumab combination will be further evaluated at the Recommended Phase 2 Dose (RP2D) established in the dose- escalation part, (10 µg/kg/dose), in an expansion cohort of subjects with advanced/metastatic carcinoma of the esophagus.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Dose Escalation naptumomab estafenatox 2 µg/kg and durvalumab
NAP was administered on the first four days of each 21-day cycle, at daily doses of 2 µg/kg. Durvalumab (1120 mg, IV, 1- 1.5 hours after completion of the administration of NAP) was administered on the second day of each 21-day cycle. After cycle 3, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Naptumomab estafenatox and durvalumab
NAP was given as an intravenous (I.V.) bolus injection at multiple doses. Durvalumab was given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Dose Escalation naptumomab estafenatox 5 µg/kg and durvalumab
NAP was administered on the first four days of each 21-day cycle, at daily doses of 5 µg/kg. Durvalumab (1120 mg, IV, 1- 1.5 hours after completion of the administration of NAP) was administered on the second day of each 21-day cycle. After cycle 3, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Naptumomab estafenatox and durvalumab
NAP was given as an intravenous (I.V.) bolus injection at multiple doses. Durvalumab was given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Dose Escalation naptumomab estafenatox 10 µg/kg and durvalumab
NAP was administered on the first four days of each 21-day cycle, at daily doses of 10 µg/kg. Durvalumab (1120 mg, IV, 1- 1.5 hours after completion of the administration of NAP) was administered on the second day of each 21-day cycle. After cycle 3, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Naptumomab estafenatox and durvalumab
NAP was given as an intravenous (I.V.) bolus injection at multiple doses. Durvalumab was given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Dose Escalation naptumomab estafenatox 15 µg/kg and durvalumab
NAP was administered on the first four days of each 21-day cycle, at daily doses of 15 µg/kg. Durvalumab (1120 mg, IV, 1- 1.5 hours after completion of the administration of NAP) was administered on the second day of each 21-day cycle. After cycle 3, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Naptumomab estafenatox and durvalumab
NAP was given as an intravenous (I.V.) bolus injection at multiple doses. Durvalumab was given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Dose Escalation naptumomab estafenatox 20 µg/kg and durvalumab
NAP was administered on the first four days of each 21-day cycle, at daily doses of 20 µg/kg. Durvalumab (1120 mg, IV, 1- 1.5 hours after completion of the administration of NAP) was administered on the second day of each 21-day cycle. After cycle 3, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Naptumomab estafenatox and durvalumab
NAP was given as an intravenous (I.V.) bolus injection at multiple doses. Durvalumab was given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Dose escalation, obinutuzumab pretreatment followed by NAP 10 µg/kg and durvalumab
Obinutuzumab (1000 mg/day) was administered on days 13 and 12 prior to the first day of NAP. NAP was administered on the first four days of each 21-day cycle, at daily doses of 10 µg/kg. Durvalumab (1120 mg, IV, 1- 1.5 hours after completion of the administration of NAP) was administered on the second day of each 21-day cycle. After cycle 3, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Obinutuzumab, naptumomab estafenatox and durvalumab
Obinutuzumab is given intravenous (I.V.) 1,000 mg concentrate for solution for infusion, as pre-treatment.
Dose escalation and MTD Expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses.
Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Esophageal cohort expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses on cycles 1-6 and one dose per cycle starting cycle 7. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle during cycles 1-6, and at a dose of 1500 mg delivered once every 28 days starting cycle 7.
Dose escalation, obinutuzumab pretreatment followed by NAP 15 µg/kg and durvalumab
Obinutuzumab (1000 mg/day) was administered on days 13 and 12 prior to the first day of NAP. NAP was administered on the first four days of each 21-day cycle, at daily doses of 15 µg/kg. Durvalumab (1120 mg, IV, 1- 1.5 hours after completion of the administration of NAP) was administered on the second day of each 21-day cycle. After cycle 3, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Obinutuzumab, naptumomab estafenatox and durvalumab
Obinutuzumab is given intravenous (I.V.) 1,000 mg concentrate for solution for infusion, as pre-treatment.
Dose escalation and MTD Expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses.
Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Esophageal cohort expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses on cycles 1-6 and one dose per cycle starting cycle 7. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle during cycles 1-6, and at a dose of 1500 mg delivered once every 28 days starting cycle 7.
MTD expansion, obinutuzumab pretreatment with NAP at MTD and durvalumab
NAP at 15mcg/kg and durvalumab (1120 mg) were given for 6 cycles after pre-treatment of obinutuzumab (1000 mg/day) on D-13 and D-12. After cycle 6, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Obinutuzumab, naptumomab estafenatox and durvalumab
Obinutuzumab is given intravenous (I.V.) 1,000 mg concentrate for solution for infusion, as pre-treatment.
Dose escalation and MTD Expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses.
Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Esophageal cohort expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses on cycles 1-6 and one dose per cycle starting cycle 7. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle during cycles 1-6, and at a dose of 1500 mg delivered once every 28 days starting cycle 7.
MTD expansion, obinutuzumab pretreatment with NAP, at the previous dose level, and durvalumab
NAP, at the previous dose level (10mcg/kg), and durvalumab (1120 mg) were given for 6 cycles after pre-treatment of obinutuzumab (1000 mg/day) on D-13 and D-12. After cycle 6, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Obinutuzumab, naptumomab estafenatox and durvalumab
Obinutuzumab is given intravenous (I.V.) 1,000 mg concentrate for solution for infusion, as pre-treatment.
Dose escalation and MTD Expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses.
Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Esophageal cohort expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses on cycles 1-6 and one dose per cycle starting cycle 7. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle during cycles 1-6, and at a dose of 1500 mg delivered once every 28 days starting cycle 7.
MTD expansion, abbreviated regimen of obinutuzumab pretreatment with NAP at MTD and durvalumab
NAP at MTD (10 mcg/kg/day) and durvalumab (1120 mg) were given for 6 cycles after a single dose of pre-treatment of obinutuzumab (1000 mg/day) on D-7. After cycle 6, patients continued to receive durvalumab alone at a dose of 1500 mg delivered once every 28 days, until confirmed disease progression or unacceptable toxicity for a maximum of up to 24 months.
Obinutuzumab, naptumomab estafenatox and durvalumab
Obinutuzumab is given intravenous (I.V.) 1,000 mg concentrate for solution for infusion, as pre-treatment.
Dose escalation and MTD Expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses.
Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Esophageal cohort expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses on cycles 1-6 and one dose per cycle starting cycle 7. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle during cycles 1-6, and at a dose of 1500 mg delivered once every 28 days starting cycle 7.
Cohort Expansion in Esophageal Cancer: Obinutuzumab pretreatment, NAP and Durvalumab
NAP will be administered at a dose of 10 μg/kg/day by IV bolus on Days 1 through 4 of the first 6 treatment cycles, and durvalumab will be administered at a flat dose of 1120 mg on Day 2 of each of the first 6 treatment cycles. Starting Cycle 7, a single administration of NAP at the same dose and durvalumab at the dose of 1500 mg will be administered on the same day (Day 1) in 28-day treatment cycles. The first 6 treatment cycles will be 21 days in duration and, starting Cycle 7 onward, treatment cycles will be 28 days in duration. Study treatment will continue until disease progression, untoward toxicity, noncompliance, or for a maximum duration of 2 years.
Obinutuzumab, naptumomab estafenatox and durvalumab
Obinutuzumab is given intravenous (I.V.) 1,000 mg concentrate for solution for infusion, as pre-treatment.
Dose escalation and MTD Expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses.
Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Esophageal cohort expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses on cycles 1-6 and one dose per cycle starting cycle 7. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle during cycles 1-6, and at a dose of 1500 mg delivered once every 28 days starting cycle 7.
Interventions
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Naptumomab estafenatox and durvalumab
NAP was given as an intravenous (I.V.) bolus injection at multiple doses. Durvalumab was given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Obinutuzumab, naptumomab estafenatox and durvalumab
Obinutuzumab is given intravenous (I.V.) 1,000 mg concentrate for solution for infusion, as pre-treatment.
Dose escalation and MTD Expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses.
Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle, and when administered as monotherapy at a dose of 1500 mg delivered once every 28 days.
Esophageal cohort expansion: NAP is given as an intravenous (I.V.) bolus injection at multiple doses on cycles 1-6 and one dose per cycle starting cycle 7. Durvalumab is given at a dose of 1120 mg, I.V, 1- 1.5 hours after completion of the administration of NAP on the second day of each 21-day cycle during cycles 1-6, and at a dose of 1500 mg delivered once every 28 days starting cycle 7.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
b. Esophageal Cohort Expansion: i. Group 1 - no prior CPI: Subjects with only ESCC who may have received up to 1 prior chemotherapy as a line for metastatic disease or up to 2 prior chemotherapies if they also received neoadjuvant/adjuvant systemic therapy, but no prior CPI.
If subjects received prior chemotherapy for metastatic disease, they should have documented radiographic or clinical progression.
ii. Group 2 - prior CPI: Subjects with either ESCC or AC of the esophagus or GEJ (Siewert type 1) who must not have had more than 2 prior lines of therapy. Patients will be allowed to have up to 2 prior regimens for metastatic disease, or up to 3 prior therapies if they also received neoadjuvant/adjuvant systemic therapy.
Subjects are eligible provided that they have received CPI therapy for at least 9 weeks, provided that they have documented progression of their disease on such therapy, and provided that the prior CPI was not discontinued for toxicity.
No more than 1 prior CPI treatment is allowed (prior combination of anti-PD-\[L\]1 and anti-CTLA-4 is acceptable).
Subjects with AC that is HER 2/neu negative.
9. Subjects with known, suspected, or documented parenchymal brain metastases, unless treated with surgery and/or radiation, with the subject neurologically stable and off pharmacologic doses of systemic glucocorticoids (equivalent to \< 10 mg/day of prednisone); subjects with leptomeningeal metastases are not eligible. Subjects should have completed brain radiation at least 14 days before start of obinutuzumab treatment.
10. Prior treatment with chemotherapy or other systemic antineoplastic therapy within 21 days; prior experimental therapy within 21 days or 5 half-lives, whichever is shorter.
11. The use of immunosuppressive agents within 28 days of obinutuzumab administration including, but not limited to, cyclosporine, mycophenolate, azathioprine, methotrexate, adalimumab, infliximab, vedolizumab, tofacitinib, dupilumab, rituximab, etc. Pharmacologic doses of glucocorticoids defined as glucocorticoid equivalents of \> 10 mg/day of prednisone (except when required for study medications or used prior to administration of radiographic contrast material in subjects with allergies) are not acceptable within 14 days of obinutuzumab administration. Subjects are permitted to receive topical, intranasal, inhalational, and intra ocular glucocorticoids.
12. Adequate hematologic and organ function:
1. White blood cells (WBC) ≥ 3000/μL
2. Absolute neutrophil count (ANC) ≥ 1500/μL
3. Platelets ≥ 100,000/μL
4. Hemoglobin ≥ 9 g/dL
5. Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance (CrCL) \> 40 mL/sec by Cockcroft-Gault (using actual body weight)
6. Aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) ≤ 2.5 × ULN (for patients with known liver involvement AST and ALT ≤ 5 × ULN); bilirubin ≤ 1.5 mg/dL (unless diagnosed with Gilbert's syndrome)
7. International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Subjects on anticoagulant therapy should be discussed with the Medical Monitor.
13. Patients must be willing and able to comply with scheduled visits, drug administration plan, hospitalization for treatment (if needed) and scheduled follow-up visits and examinations as outlined in the protocol, including procedures undertaken to perform fresh tumor biopsies if needed.
14. Must have a life expectancy of at least 3 months.
15. Negative pregnancy test (serum) for women of childbearing potential.
16. Female participants must be ≥ 1 year post-menopausal, surgically sterile, or using 1 highly effective form of birth control (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.) Women of childbearing potential must agree to use 1 highly effective method of birth control. They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study until 90 days after the last dose of NAP + durvalumab combination therapy or durvalumab monotherapy. Non sterilized male partners of a female subject of childbearing potential must use a male condom plus spermicide throughout this period.
17. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of Screening throughout the total duration of the study and until 90 days after the last dose of NAP + durvalumab combination therapy or durvalumab monotherapy to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period.
18 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
NeoTX Therapeutics Ltd.
INDUSTRY
Responsible Party
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Principal Investigators
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Tal Hetzroni Kedem
Role: STUDY_DIRECTOR
NeoTX Therapeutics Ltd.
Locations
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Shalby Hospital
Ahmedabad, Gujarat, India
National Cancer Institute
Jhajjar, Haryana, India
All India Institute of Medical Sciences
New Delhi, New Delhi, India
PMCH (Pacific Medical College & Hospital)
Udaipur, Rajasthan, India
Basavatarakam Indo-American Cancer Hospital & Research Institute
Hyderabad, Telangana, India
Rambam Medical Center
Haifa, , Israel
Rabin Medical Center
Petah Tikva, , Israel
Sheba Medical Center
Ramat Gan, , Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, , Israel
Countries
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Other Identifiers
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127-CL-01 (NT-NAP-101)
Identifier Type: -
Identifier Source: org_study_id
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