Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumor, Including a Cohort Expansion in Esophageal Cancer.

Sponsor
NeoTX Therapeutics Ltd.
Study ID
NCT03983954
Phase
PHASE1
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Obinutuzumab, naptumomab estafenatox and durvalumab — COMBINATION_PRODUCT
    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.
  • Naptumomab estafenatox and durvalumab — COMBINATION_PRODUCT
    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.

Study Details

This Phase 1b is a dose escalation, MTD expansion and cohort expansions study to assess the safety and tolerability of a combination of NAP with durvalumab in subjects with selected advanced or metastatic solid tumors.

Key Dates

First listed
Jun 12, 2019
Start date
Oct 10, 2019
Status verified
Nov 2025
Primary completion
Mar 1, 2027
Completion
Mar 1, 2027

Study Design

Enrollment
120 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.

Primary Outcome Measure

Part A: Dose Escalation / MTD Expansion: The incidence and characteristics of adverse events, associated with ascending doses of NAP in combination with a set dose of durvalumab [ Time Frame: From day 1 up to 90 days following last dose of study drug ]

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