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Endometrial CarcinomaPhase 1/2GYNETNCT04652076

GYNecological Cancers Treated with NETrin MAbs in Combination with Chemotherapy and /or Pembrolizumab

A Phase 1/2 study testing NP137, Pembrolizumab and Paclitaxel in people with Endometrial Carcinoma and Cervix Carcinoma, run by NETRIS Pharma at 15 sites in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with pembrolizumab and/or chemotherapies in patients with advanced/metastatic gynecological cancers (2 types: endometrial carcinoma and cervix carcinoma). Read more about this study

Who is it for?
Ages 18 years and older, women onlyHealthy volunteers can take part
Conditions the study is for
Endometrial Carcinoma, Cervix Carcinoma
What is being tested?
NP137, Pembrolizumab and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
240 participants
Where
15 sitesFrance
Study dates
14 Dec 2020to 30 Jul 2026
Phase
Phase 1/2
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
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Be women ≥ 18 years at time of inform consent signature.
  • Patient with histologically confirmed locally advanced / metastatic endometrial carcinoma (Endometrial sarcoma are excluded) or patient with histologically confirmed locally advanced / metastatic cervix adeno- or epidermoid- carcinoma.
  • Previously treated by at least one line of platinum based chemotherapy, but no more than 3 lines of chemotherapies whatever the nature. If the previous based platinum chemotherapy was given as neoadjuvant or adjuvant chemotherapy for a local disease (stage I or II), inclusion must be performed no more than one year after the end of this chemotherapy, except if an advanced or metastatic relapse has been documented and treated by a systemic anti-cancer agent during this time interval.
  • In all cases, a minimal wash-out period of 6 months after completion of last chemotherapy with [platinum + paclitaxel] is required prior to entering the study.
  • Platinum chemotherapy concomitant to RT can not be considered as a line of previous platinum based chemotherapy.
  • For endometrium carcinoma: mutational profile (MSI/MSS status) available before randomization (see St Paul de Vence 2019- ARCAGY - GINECO Group recommendation).
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  • Documented disease progression as per RECIST V1.1 after prior systemic chemotherapy regimen and presence of at least one lesion evaluable for response according to RECIST 1.1.
  • Have provided a representative archival tumor sample in formalin-fixed paraffin embedded (FFPE) block (primary tumor or metastasis) or newly obtained core or excisional biopsy of a tumor lesion together with an associated pathology report.
  • Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut (details pertaining to tumor tissue submission can be found in the laboratory manual).
  • Optional for patients having consented to tumor biopsies: presence of at least one tumor lesion visible by medical imaging and accessible to repeatable percutaneous sampling that permits core needle biopsy without unacceptable risk of a significant procedural complications, and suitable for retrieval of 4 cores using a 16-gauge diameter needle or larger.
  • Note: lesions to be biopsied should not be selected as RECIST target lesions. Bone lesions are not adequate lesions for biopsies and lymph nodes lesions should not be considered as prime targets.
  • Life expectancy ≥ 3 months.
  • Eastern Cooperative Oncology GrougGroup performance status (ECOG PS) of 0 to 1.
  • Demonstrate adequate cardiovascular function:
  • QTcF < 470ms
  • Resting BP systolic <160mmHg and diastolic < 100mmHg
  • LVEF > 50% as determined by transthoracic echocardiogram.
  • Demonstrate adequate organ function as defined in protocol, all screening laboratory tests should be performed within 7 days prior C1D1:
  • Women of child-bearing potential must have a negative urine pregnancy test at screening (within 72 hours prior C1D1) and must agree to use 2 effective forms of contraception from the time of the treatment period and of the negative pregnancy test up 6 months after the end of their treatment.
  • Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures.
  • Patient should be able and willing to comply with study visits and procedures as per protocol.

Who cannot join

  • Patients with progression during previous chemotherapy with [platinum +paclitaxel]
  • Persistence of CTCAE ≥ Grade 2 toxicity due to prior anti-cancer therapy (except alopecia (any grades).
  • History of severe (≥Grade 3) allergic anaphylactic reactions to one of the components of NP137, pembrolizumab, paclitaxel, carboplatin and/or any of their excipients.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years.
  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
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  • Prior/concomitant Therapy:
  • Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade ≥ 3 irAE
  • Have received prior systemic anti-cancer therapy :
  • Chemotherapy or targeted therapies (approved or investigational) within 2 weeks or 5* t1/2 whichever is longer prior C1D1.
  • Hormonal therapy within 1 week prior to C1D1
  • Biological therapy within 4 weeks prior to C1D1
  • Are currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. Have received prior radiotherapy within 4 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
  • Have had major surgery within 4 weeks of start of study treatment. Participants must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment, C1D1.
  • Have received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Note: killed vaccinesare allowed.
  • Have received immunosuppressive medication within 2 weeks with the exceptions of intranasal, topical and inhaled corticosteroids or systemic corticosteroids at doses which are not to exceed 10 mg/day of prednisone, or equivalent doses of another corticosteroid.
  • Have a history of autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. History of autoimmune disease which include but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:
  • Patients with a history of autoimmune-related hypothyroidism who are on stable thyroid replacement hormone therapy,
  • Patients with controlled Type 1 diabetes mellitus,
  • patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are eligible provided that they meet the following conditions:
  • Rash must cover less than 10% of body surface area (BSA).
  • Disease is well controlled at baseline and only requiring low potency topical steroids.
  • No acute exacerbations of underlying condition within the previous 12 months requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoid, biologic agents, oral calcineurin inhibitors, high potency or oral steroids.
  • Patients with HIV, active B or C hepatitis infection. Notes: Active hepatitis B i.e. chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening before C1D1. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. HBV DNA test must be performed in these patients prior to C1D1. Patients with a positive HBcAb test must have a negative HBV DNA test at screening. Active hepatitis C i.e. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA at screening.
  • Patients with active tuberculosis.
  • Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past.
  • History of idiopathic pulmonary fibrosis, non-infectious pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease , drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
  • Have an active infection requiring systemic therapy.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

France15 sites

  • CHRU BESANCON - Hopital Jean Minjoz

    Besançon

  • Institut Bergonié

    Bordeaux

  • Centre François Baclesse

    Caen

  • Centre Georges François Leclerc

    Dijon

  • Primary Completion Date

    Lille

  • Centre Léon Bérard

    Lyon

  • Primary Completion Date

    Marseille

  • ICM - Val d'Aurelle

    Montpellier

  • Insitut de cancérologie de l'ouest

    Nantes

  • Hopital de la Croix Saint Simon

    Paris, 75020

  • Institut Curie (Site Saint Cloud)

    Paris, 92210

  • Institut Gustave Roussy

    Paris, 94800

  • Aphp Cochin

    Paris

  • Centre Eugène Marquis

    Rennes

  • Institut claudius Regaud

    Toulouse

Other trials in France

About this study

Official title: A Randomized, Multicenter, Open Label, Phase I/II Study to Evaluate the Safety, Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination with Carboplatin Plus Paclitaxel And/or Pembrolizumab in Patients with Locally Advanced/metastatic Endometrial Carcinoma or Cervix Carcinoma Progressing/relapsing After At Least One Prior Systemic Chemotherapy.

The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with pembrolizumab and/or chemotherapies in patients with advanced/metastatic gynecological cancers (2 types: endometrial carcinoma and cervix carcinoma).

Read the detailed description

The prognosis of patients with locally advanced/metastatic uterine (endometrial or cervical) cancer progressing/relapsing after at least one prior systemic treatment remains poor. The development of new innovative anti-tumor drug candidates as single agent or in combination with chemotherapy or check point inhibitors is needed.

NP137 is a first-in-class humanized monoclonal antibody targeting specifically and selectively Netrin-1. By blocking Netrin-1, NP137 is capable of restoring apoptosis in tumor cells in vitro and in vivo, leading to therapeutic activity in various animal cancer models.

Dependence receptors inhibitor such as NP137 might be a novel choice to improve the clinical outcomes of these patients.

The herein proposed study will be a multicenter, open-label, randomized, Phase I/II trial with:

A safety run in part to assess the safety of the therapeutic combinations for the first 6 patients enrolled in each of the therapeutic combinations independently of the tumor type. According to safety rules, these therapeutic combinations will be investigated or not in the Phase II part.

A Phase II part will be then conducted using an adaptive Bayesian approach allowing to quickly stop treatment cohorts without evidence of efficacy and/or select promising treatment cohorts. The Phase II part will be initiated with a preliminary step to assess the clinical activity of the proposed therapeutic combinations in 2 tumor types before proceeding to the activation of extension phase II part of the study. For each cohorts, clinical activity will be assessed through by sequential statistical analysis at specific timepoints.

Being tested
NP137, Pembrolizumab, Paclitaxel, Carboplatin
Keywords
anti-Netrin 1, anti-PD-1, Immunotherapy, Check Point Inhibitors, Dependence Receptors
Medical subject headings
Endometrial Neoplasms, Uterine Cervical Neoplasms

What participants receive

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

  • NP137Drug

    Recombinant humanized IgG1 monoclonal antibody against Netrin 1. NP137 will be administred IV, Q3W until disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, pregnancy or SMPC guidance, whichever occurs first.

  • PembrolizumabDrug

    Also called KEYTRUDA

    Humanised monoclonal anti-programmed cell death-1 (PD-1) antibody will be administred in IV Q3W. A maximum 35 cycles of treatments (approximately 2 years) with pembrolizumab can be administered to patients.

  • PaclitaxelDrug

    Standard Chemotherapy agent will be administred IV, Q3W, up to 6 cycles of treatment.

  • CarboplatinDrug

    Standard Chemotherapy agent will be administred IV, Q3W, up to 6 cycles of treatment.

Study groups in NCT04652076
Study groupRoleWhat they receive
Arm A: Standard Chemotherapy alone (Paclitaxel + Carboplatin)OtherStandard Chemotherapy will be adminitred in 2 independant cohorts: Endometrial carcinoma or Cervix Carcinoma
Receives: Drug: Paclitaxel; Drug: Carboplatin
Arm B: Experimental double combination [Standard Chemotherapy +NP137]OtherExperimental double combination [Standard Chemotherapy +NP137] will be administred in 2 independant cohorts: Endometrial carcinoma or Cervix Carcinoma
Receives: Drug: NP137; Drug: Paclitaxel; Drug: Carboplatin
Arm C: Experimental double combination [Pembrolizumab +NP137]OtherExperimental double combination [Pembrolizumab +NP137] will be administred in 2 independant cohorts: Endometrial carcinoma or Cervix Carcinoma
Receives: Drug: NP137; Drug: Pembrolizumab
Arm D: Experimental triple therapeutical combination [Pembrolizumab+ Standard Chemotherapy + NP137]OtherExperimental triple combination [Pembrolizumab+ Standard Chemotherapy + NP137] will be administred in 2 independant cohorts: Endometrial carcinoma or Cervix Carcinoma
Receives: Drug: NP137; Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin

What is being measured

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

  1. DLT occurrence

    Any pre-definied toxicities graded by using NCI CTCAE Version 5.0 and assessed by the investigator to be possibly, probably, or definitely related to study treatments administration during the safety run in period

    Measured: Safety run in Period: At the end of Cycle 2 (each cycle is 21 days) for the first 6 to 12 patients per arm

  2. Overall response Rate (ORR)

    Rate of patients with CR or PR as per RECIST 1.1

    Measured: At 3 months of treatement and then every 12 weeks, up to 2 years

Secondary outcomes (11)

  1. Clinical Benefit Rate (CBR)

    The proportion of evaluable patients with an objective response according to RECIST 1.1.

    Measured: Every 12 weeks, up to 2 years

  2. Duration of Response

    Time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression or death is documented,

    Measured: Every 12 weeks, up to 2 years

  3. Progression-free Survival

    Time from first study drug intake until disease progression or death, whichever occurs first

    Measured: Every 12 weeks, up to 2 years

  4. Overall Survival

    Time from the first day of study treatment to the date of death due to any cause.

    Measured: Every 12 weeks, up to 2 years

  5. Best Overall Response

    The best response designation between the date of the first study treatment and the date of objectively documented progression or the date of subsequent anti-cancer therapy

    Measured: Every 12 weeks, up to 2 years

  6. Pharmacokinetic parameter: Cmax

    Plasma peak concentration

    Measured: Over the first 6 cycles (each cycle is 21 days) of patients treated with NP137 and enrolled during the Safety run in period

  7. Pharmacokinetic parameter: tmax

    Time to reach the peak concentration

    Measured: Over the first 6 cycles (each cycle is 21 days) of patients treated with NP137 and enrolled during the Safety run in period

  8. Pharmacokinetic parameter: AUCt

    Area under the concentration-time curve from time zero to the last sample with the quantifiable concentration

    Measured: Over the first 6 cycles (each cycle is 21 days) of patients treated with NP137 and enrolled during the Safety run in period

  9. Pharmacokinetic parameter: AUC∞

    Area under the concentration-time curve from time zero to infinity corresponding to the definite integral of a curve that describes the variation of a drug concentration in blood plasma as a function of time (drug exposure in plasma)

    Measured: Over the first 6 cycles (each cycle is 21 days) of patients treated with NP137 and enrolled during the Safety run in period

  10. Pharmacokinetic parameter: CL

    Clearance: volume of plasma from which NP137 is completely removed per unit time.

    Measured: Over the first 6 cycles (each cycle is 21 days) of patients treated with NP137 and enrolled during the Safety run in period

  11. Pharmacokinetic parameter: t1/2

    Terminal elimination half-life: time required for the amount of NP137 in the body to decrease by half.

    Measured: Over the first 6 cycles of the patients Treated with NP137 and enrolled during the Safety run in period

Timeline

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

  1. First posted3 Dec 2020
  2. Study start14 Dec 2020
  3. Primary completion30 Oct 2025 (estimated)
  4. Study completion30 Jul 2026 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
240 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04652076
Sponsor's protocol ID
NP137CT02
Other IDs
2020-000172-38, /ET20-049, ANR-18-RHUS-0009, KEYNOTE-A92
Acronym
GYNET
Status last verified
Oct 2024
First submitted
5 Nov 2020
Last updated
8 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NP137, Pembrolizumab and Paclitaxel in people with Endometrial Carcinoma and Cervix Carcinoma, run by NETRIS Pharma at 15 sites in France.

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 21 inclusion and 28 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: status not confirmed, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in France. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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?

DLT occurrence (time frame: Safety run in Period: At the end of Cycle 2 (each cycle is 21 days) for the first 6 to 12 patients per arm). The study lists 2 primary outcomes in all. 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 NCT04652076.

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 8 Oct 2024.

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