Naptumomab Estafenatox in Combination With Pembrolizumab Preceded by Obinutuzumab in Patients With Urothelial Cancers

NCT05894447 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 22-10025226
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to test the safety and tolerability of naptumomab estafenatox (NAP), the planned experimental (investigational) drug, in combination with pembrolizumab following a single pretreatment with Obinutuzumab (Obi), and determine its side effects and effects on urothelial cancer. It is hypothesized that adding NAP will make pembrolizumab more effective. Participants will receive 2 infusions of Obi prior to the treatment of NAP in combination with pembrolizumab. This treatment is given in 21-day cycles for 6 cycles with NAP administered daily for 4 consecutive days, Days 1-4, + pembrolizumab given on day 2 of each cycle. After these six cycles of therapy, participants will continue to receive pembrolizumab every 3 weeks, without NAP, for a total number of up to 34 pembrolizumab administrations since cycle 1. After the treatment of Obi is completed, participants will start NAP in combination with pembrolizumab and continue that treatment in a 28 day cycle period. NAP will be given for a total of 6 cycles and pembrolizumab will be given every 21 days for a total of up to 2 years. After stopping treatment, participants have follow-up visits or phone calls about every 12 weeks until the study is closed.

Conditions

Urothelial Carcinoma

Keywords

Pembrolizumab; obinutuzumab; naptumomab estafenatox; Urothelial Cancer

Outcome Measures

Primary Outcomes (1)

• Recommended Phase 2 Dose (RP2D) of the combination of NAP/pembrolizumab preceded by obinutuzumab to find the

  The RP2D will be determined based on the maximum tolerated dose (MTD) observed in the trial as well as other factors such as AE profiles observed, correlative analyses, etc. It will not be a dose level that is greater than the MTD. The MTD will be the highest dose that results in less than 25% dose limiting toxicities as described in the protocol based on the CTCAE v5.0.

  Day 21

Secondary Outcomes (6)

• Objective response rate (ORR) based on the RECIST 1.1 criteria

  Until disease progression or death, for a maximum of approximately 4 years

• Median duration of response (DOR) in subjects who achieve an objective response (CR or PR)

  Until disease progression or death, whichever occurs first, for a maximum of approximately 4 years

• Progression-free survival (PFS)

  Until disease progression or death, whichever occurs first, for a maximum of approximately 4 years

• 6-month Progression-Free Survival (6-PFS)

  6 months from treatment initiation

• Number of adverse events (AEs) associated with the investigational drug combination

  AEs will be assessed from the time of informed consent until 30 days after the last dose of study treatment.

Study Arms (1)

Naptumomab estafenatox in combination with pembrolizumab preceded by Obinutuzumab

EXPERIMENTAL

The study will test two doses of NAP 5 µg/kg/day IV (Dose Level 1) and 10 µg/kg/day IV (Dose Level 2), in combination with a fixed dose of pembrolizumab (200mg IV every 3 weeks). NAP will be given on Days 1-4 of each 21 day cycle for 6 cycles. Pembrolizumab will be given on Day 2 of each 21-day treatment cycle for the first 6 cycles and then as monotherapy every 21 days for up to a total of 34 administrations. Two doses of Obinutuzumab 1,000 mg IV will be given before starting NAP and pembrolizumab on Days - 13 and -12. Pembro 200 mg i.v. Day 2 of each 21-day treatment cycle for the first 6 cycles

Drug: Naptumomab Estafenatox; Drug: Pembrolizumab; Drug: Obinutuzumab

Interventions

Naptumomab Estafenatox DRUG

5 or 10 µg/kg IV naptumomab estafenatox will be given on the first four days of every 21-day treatment cycle for 6 cycles

Naptumomab estafenatox in combination with pembrolizumab preceded by Obinutuzumab

Pembrolizumab DRUG

200 mg IV pembrolizumab will be given on day 2 of each 21 day cycle for up to 24 cycles

Also known as: Keytruda

Naptumomab estafenatox in combination with pembrolizumab preceded by Obinutuzumab

Obinutuzumab DRUG

Two doses of 1,000 mg IV obinutuzumab given prior to starting pembrolizumab and naptumomab estafenatox

Also known as: Gazyva

Naptumomab estafenatox in combination with pembrolizumab preceded by Obinutuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must provide signed informed consent prior to any study specific procedures that are not part of standard medical care
• At least 18 years of age
• Must have advanced or metastatic disease at the time of enrollment.
• Must have histologically and/or cytologically confirmed evidence of predominantly transitional cell urothelial cancer (carcinomas of the renal pelvis, ureter, urinary bladder or urethra)
• Must have received no more than 2 prior lines of therapy for advanced or metastatic disease; patients may have received adjuvant/neoadjuvant therapy which must have been completed prior to entry into the current trial
• Must be willing and able to comply with scheduled visits, procedures, drug administration plan, etc. as outlined in the protocol
• Have an estimated life expectancy of at least 12 weeks
• COVID-19 vaccine is not mandatory. However, patients who have been vaccinated against COVID-19 prior to study entry, should fulfill the following conditions:
• The patient completed the primary series vaccination (initial 2 doses of the vaccine)
• At least 14 days have passed since the last dose (primary or booster) before receiving Obi pretreatment

You may not qualify if:

• Active infection requiring treatment within 3 days of enrollment
• Other active neoplastic disease (cancer) requiring concurrent anti-neoplastic treatment
• Known, suspected or documented parenchymal brain metastases unless patient is stable after being treated with surgery and/or radiation
• Active or previously documented autoimmune or inflammatory disorders such as, but not limited to rheumatoid arthritis, systemic lupus erythematosus, uveitis, ulcerative colitis, Crohn's syndrome, Wegener's syndrome, multiple sclerosis, myasthenia gravis, scleroderma, and sarcoidosis
• The following are exceptions to this criterion:
• Vitiligo or psoriasis not requiring systemic treatment (within the last 2 years)
• Endocrinopathies (e.g., following Hashimoto syndrome) stable on hormone replacement or do not require any therapy
• History of primary immunodeficiency
• History or prior allogeneic organ transplant 7. The use of immunosuppressive agents within 28 days of enrollment (D-13; obinutuzumab pretreatment) including, but not limited to, cyclosporine, mycophenolate, azathioprine, methotrexate, adalimumab, infliximab, vedolizumab, tofacitinib, dupilumab, rituximab, etc. and including pharmacologic doses of glucocorticoids defined as glucocorticoid equivalents of \>10 mg/day of prednisone (with the exception of systemic steroids given as a premedication before each of the study medications, or used prior to administration of radiographic contrast material in subjects with allergies) are not acceptable within 14 days prior to enrollment. Subjects are permitted to receive topical, intranasal, inhalational, and intra-ocular glucocorticoids
• Have received a live attenuated vaccine within 28 days prior to the first dose of Obi
• HIV infection that is not considered well-controlled
• Pregnant or breastfeeding
• Participants of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of study treatment
• Participation in an investigational drug study within the past 4 weeks
• Major surgery or trauma within 4 weeks of study entry (D-13; obinutuzumab pre-treatment)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• NeoTX Therapeutics Ltd.: collaborator

Study Sites (1)

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

naptumomab estafenatox; pembrolizumab; obinutuzumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Cora Sternberg, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2023
• First Posted: June 8, 2023
• Study Start: November 1, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)