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Urothelial CarcinomaPhase 1NCT05894447

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

A Phase 1 study testing Naptumomab Estafenatox, Pembrolizumab and Obinutuzumab in people with Urothelial Carcinoma, run by Weill Medical College of Cornell University at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
Naptumomab Estafenatox, Pembrolizumab and Obinutuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Nov 2023to Jun 2028
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
Show all 19Show fewer
  • 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)
  • Previous treatment with one of the study drugs (NAP, pembro or Obi)
  • Certain cardiovascular conditions like current or recent CHF, myocardial infarction, acute coronary syndrome, ongoing angina pectoris, severe peripheral vascular disease, or CVA (stroke). Your doctor will discuss eligibility with you in more detail
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  • History of progressive multifocal leukoencephalopathy (PML)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Weill Cornell Medicine/NewYork-Presbyterian Hospital

    New York, New York, 10021

Other trials in United States

About this study

Official title: A Phase 1 Trial of Naptumomab Estafenatox (NAP) in Combination With Pembrolizumab (Pembro) Preceded by Obinutuzumab (Obi) in Patients With Urothelial Cancers

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.

Read the detailed description

This is a Phase 1, open-label, prospective, dose-finding and cohort expansion study to assess the safety, tolerability, pharmacodynamics and preliminary antitumor activity of the combination of NAP/pembrolizumab following pretreatment with Obi in patients with urothelial cancers who are candidates for pembrolizumab treatment. and will not be used to determine eligibility for enrollment.

The study will test two doses of NAP 5 µg/kg/day (Dose Level 1) and 10 µg/kg/day (Dose Level 2), in combination with a fixed dose of pembrolizumab (200mg every 3 weeks). It is expected that full dose of both drugs can be safely combined. The purpose of this study is to define the recommended dose for phase 2 trials of the combination of NAP/pembrolizumab by employing a BOIN design for phase 1 trials. The BOIN design will find the highest dose for which the probability of a dose-limiting toxicity is less than 0.25. No dose level will have more than 12 patients. An initial cohort of 3 patients will be enrolled on Dose Level 1. After these patients have been observed for a DLT, the decision to escalate, de-escalate or remain at the current dose will be made according to the table in the statistical section of the protocol. The maximum tolerated dose (MTD) will be selected using isotonic regression that pools the information across doses. No intra-patient dose escalation is permitted. Patients who discontinue the study during the 21-day dose-limiting toxicity (DLT) observation period for reasons other than a DLT, or who do not receive a full cycle of NAP/pembrolizumab, will be replaced.

Each patient will participate in 3 stages of the trial: a 21-day screening stage, followed by a treatment stage that may continue until evidence of progressive neoplastic disease, intolerance to treatment of fulfillment of any of the other criteria for treatment discontinuation as listed in Section 8.1 of the protocol, and a follow-up phase to determine the effect of protocol treatment on cancer progression. All patients will be seen at the end of treatment (EOT) visit 30 (+ 7) days after the last dose of protocol therapy.

Being tested
Naptumomab Estafenatox, Pembrolizumab, Obinutuzumab
Keywords
Pembrolizumab, obinutuzumab, naptumomab estafenatox, Urothelial Cancer
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Naptumomab EstafenatoxDrug

    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

  • PembrolizumabDrug

    Also called Keytruda

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

  • ObinutuzumabDrug

    Also called Gazyva

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

Study groups in NCT05894447
Study groupRoleWhat they receive
Naptumomab estafenatox in combination with pembrolizumab preceded by ObinutuzumabExperimentalThe 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
Receives: Drug: Naptumomab Estafenatox; Drug: Pembrolizumab; Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Day 21

Secondary outcomes (6)

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

    The objective response rate will be determined as the number of patients with a confirmed PR or CR (via RECIST v1.1) divided by the total number of patients evaluable for objective response.

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

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

    DOR is defined as the time from first evidence of response (CR or PR) to progressive disease or death, whichever occurs first. Progressive disease is defined per RECIST v1.1 criteria. The DOR will only be evaluated for patients with a confirmed response. Patients who had a confirmed response and are alive without documented disease progression will be censored at the time of their last disease evaluation. If more than 50% of the responders had experienced a progression/death, the median DOR will be estimated with a corresponding 95% CI.

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

  3. Progression-free survival (PFS)

    PFS is defined as the time from start of study treatment to progression or death from any cause. Living subjects with no PD will be censored at the date of the last evaluable response assessment.

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

  4. 6-month Progression-Free Survival (6-PFS)

    6- month PFS is defined as the time from start of study treatment to progression or death from any cause, as assessed at 6 months. Living subjects with no PD will be censored at the date of the last evaluable response assessment.

    Measured: 6 months from treatment initiation

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

    Adverse reactions will be graded as per National Cancer Institute (NCI) Common Terminology Criteria (CTC) version 5.

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

  6. 12-Month Progression-Free Survival (12-PFS)

    12-month Progression-Free Survival is defined as time from start of study treatment to progression or death from any cause, as assessed at 12 months. Living subjects with no PD will be censored at the date of the last evaluable response assessment.

    Measured: 12 months from treatment initiation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2023
  2. Study startNov 2023 (estimated)
  3. Primary completionDec 2025 (estimated)
  4. Study completionJun 2028 (estimated)

Why it stopped: Insufficient funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05894447
Sponsor's protocol ID
22-10025226
Status last verified
Apr 2024
First submitted
30 May 2023
Last updated
12 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Naptumomab Estafenatox, Pembrolizumab and Obinutuzumab in people with Urothelial Carcinoma, run by Weill Medical College of Cornell University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase 2 Dose (RP2D) of the combination of NAP/pembrolizumab preceded by obinutuzumab to find the (time frame: Day 21). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05894447.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2024.

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