Informations générales (source: ClinicalTrials.gov)
Phase II, Multi-cohort Trial of Neoadjuvant and Post-surgery IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Selected Resectable Tumors
Interventional
Phase 2
IO Biotech (Voir sur ClinicalTrials)
décembre 2023
janvier 2027
29 juin 2024
This is a multicenter, multi-arm trial evaluating anti-tumor activity, safety, and immune
infiltration of IO102-IO103 in combination with pembrolizumab KEYTRUDA® as neoadjuvant
and post-surgery treatment. This proof-of-concept trial will include patients with
resectable tumors in at least 2 indications.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Caroline ROBERT | 01/07/2024 14:56:37 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHRU Lille - 59037 Lille - Lille - France | Sylvie Brice | Contact (sur clinicalTrials) | |||
| Hôpital Ambroise-Paré - 92104 Boulogne - Paris - France | Veronique Clerisse | Contact (sur clinicalTrials) | |||
| Institut Gustave Roussy - 94805 Villejuif - Paris - France | Myriam Maalej-Chaari | Contact (sur clinicalTrials) | |||
Critères
Tous
inclusion criteria:
• Histologically or cytologically confirmed diagnosis of cutaneous stage III melanoma
according to the American Joint Committee on Cancer (AJCC) 8th edition.
Patients with resectable tumors are eligible for this trial either at presentation for
primary melanoma with concurrent regional nodal metastasis or at the time of clinically
detected nodal recurrence; they may belong to any of the following groups:
- Primary cutaneous melanoma with clinically apparent regional lymph node metastases
- Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin
- Clinically detected primary cutaneous melanoma involving multiple regional nodal
groups
- Clinically detected nodal melanoma (if single site) arising from an unknown primary
- Relapsed resectable stage III melanoma
SCCHN-specific inclusion criteria:
• Stage III or IVA resectable locoregionally advanced SCCHN of the oral cavity,
oropharynx (with known HPV-negative or p16-negative status assessed per institution
standard or centrally), hypopharynx, or larynx.
Inclusion criteria applicable across cohorts:
In addition to the indication-specific inclusion criteria, a patient must meet all the
following general criteria to be eligible for participation in this trial:
1. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST)
1.1
2. Candidate for surgical resection with curative intent
3. The patient (or legally acceptable representative if applicable) provides written
informed consent for the trial.
4. Age ≥18 years on the day of signing the informed consent form
5. Have provided archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin
embedded (FFPE) tissue blocks are preferred to slides.
6. Eastern Cooperative Oncology Group (ECOG) performance score status of 0 or 1
7. Adequate organ function as defined below performed on screening labs obtained within
4 weeks before first dose:
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100 000/µL
- Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Note: Criterion must be met without packed
red blood cell transfusion within the prior 2 weeks. Patients can be on stable
dose of erythropoietin [≥ approximately 3 months].)
- Creatinine or measured or calculated creatinine clearance (glomerular
filtration rate can also be used in place of creatinine or creatinine
clearance) ≤1.5 × upper limit of normal (ULN) or ≥30 mL/min for patient with
creatinine levels >1.5 × institutional ULN
- Serum total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for patients with
total bilirubin levels >1.5 × ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
- International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN unless
the patient is receiving anticoagulant therapy as long as PT or partial
thromboplastin time (PTT) is within the therapeutic range of intended use of
anticoagulants
- Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is
receiving anticoagulant therapy as long as PT or PTT is within the therapeutic
range of intended use of anticoagulants
8. Women of childbearing potential: Negative urine or serum pregnancy within 72 hours
prior to receiving the first dose of trial medication. If the urine test is positive
or cannot be confirmed as negative, a serum pregnancy test will be required.
9. Women of childbearing potential: Willing to use highly effective contraception or
abstain from heterosexual activity for the duration of the trial and for at least
120 days after the last dose of trial medication
10. HIV-infected patients must be on anti-retroviral therapy (ART) and have a
well-controlled HIV infection/disease defined as:
a Patients on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening b
Patients on ART must have achieved and maintained virologic suppression defined as
confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the
limit of detection) using the locally available assay at the time of screening and for at
least 12 weeks prior to first dose of trial medication (Day 1) c Patients on ART must
have been on a stable regimen, without changes in drugs or dose modification, for at
least 4 weeks prior to first dose of trial medication (Day 1) 11. Patients who are
hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis
B (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior
to start of trial intervention.
Note: Patients should remain on anti-viral therapy throughout trial intervention and
follow local guidelines for HBV anti-viral therapy after completion of trial
intervention.
Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- Mandated by local health authority. 12. Patients with a history of hepatitis C (HCV)
infection are eligible if HCV viral load is undetectable at screening.
Note: Patients must have completed curative antiviral therapy at least 4 weeks prior to
start of trial intervention.
Hepatitis C screening tests are not required unless:
- Known history of HCV infection
- Mandated by local health authority.
Melanoma-specific
• Histologically or cytologically confirmed diagnosis of cutaneous stage III melanoma
according to the American Joint Committee on Cancer (AJCC) 8th edition.
Patients with resectable tumors are eligible for this trial either at presentation for
primary melanoma with concurrent regional nodal metastasis or at the time of clinically
detected nodal recurrence; they may belong to any of the following groups:
- Primary cutaneous melanoma with clinically apparent regional lymph node metastases
- Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin
- Clinically detected primary cutaneous melanoma involving multiple regional nodal
groups
- Clinically detected nodal melanoma (if single site) arising from an unknown primary
- Relapsed resectable stage III melanoma
SCCHN-specific inclusion criteria:
• Stage III or IVA resectable locoregionally advanced SCCHN of the oral cavity,
oropharynx (with known HPV-negative or p16-negative status assessed per institution
standard or centrally), hypopharynx, or larynx.
Inclusion criteria applicable across cohorts:
In addition to the indication-specific inclusion criteria, a patient must meet all the
following general criteria to be eligible for participation in this trial:
1. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST)
1.1
2. Candidate for surgical resection with curative intent
3. The patient (or legally acceptable representative if applicable) provides written
informed consent for the trial.
4. Age ≥18 years on the day of signing the informed consent form
5. Have provided archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin
embedded (FFPE) tissue blocks are preferred to slides.
6. Eastern Cooperative Oncology Group (ECOG) performance score status of 0 or 1
7. Adequate organ function as defined below performed on screening labs obtained within
4 weeks before first dose:
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100 000/µL
- Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Note: Criterion must be met without packed
red blood cell transfusion within the prior 2 weeks. Patients can be on stable
dose of erythropoietin [≥ approximately 3 months].)
- Creatinine or measured or calculated creatinine clearance (glomerular
filtration rate can also be used in place of creatinine or creatinine
clearance) ≤1.5 × upper limit of normal (ULN) or ≥30 mL/min for patient with
creatinine levels >1.5 × institutional ULN
- Serum total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for patients with
total bilirubin levels >1.5 × ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN
- International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN unless
the patient is receiving anticoagulant therapy as long as PT or partial
thromboplastin time (PTT) is within the therapeutic range of intended use of
anticoagulants
- Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is
receiving anticoagulant therapy as long as PT or PTT is within the therapeutic
range of intended use of anticoagulants
8. Women of childbearing potential: Negative urine or serum pregnancy within 72 hours
prior to receiving the first dose of trial medication. If the urine test is positive
or cannot be confirmed as negative, a serum pregnancy test will be required.
9. Women of childbearing potential: Willing to use highly effective contraception or
abstain from heterosexual activity for the duration of the trial and for at least
120 days after the last dose of trial medication
10. HIV-infected patients must be on anti-retroviral therapy (ART) and have a
well-controlled HIV infection/disease defined as:
a Patients on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening b
Patients on ART must have achieved and maintained virologic suppression defined as
confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the
limit of detection) using the locally available assay at the time of screening and for at
least 12 weeks prior to first dose of trial medication (Day 1) c Patients on ART must
have been on a stable regimen, without changes in drugs or dose modification, for at
least 4 weeks prior to first dose of trial medication (Day 1) 11. Patients who are
hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis
B (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior
to start of trial intervention.
Note: Patients should remain on anti-viral therapy throughout trial intervention and
follow local guidelines for HBV anti-viral therapy after completion of trial
intervention.
Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- Mandated by local health authority. 12. Patients with a history of hepatitis C (HCV)
infection are eligible if HCV viral load is undetectable at screening.
Note: Patients must have completed curative antiviral therapy at least 4 weeks prior to
start of trial intervention.
Hepatitis C screening tests are not required unless:
- Known history of HCV infection
- Mandated by local health authority.
Melanoma-specific
- Current or prior history of uveal, mucosal, or acral melanoma
- Oligometastatic stage IV melanoma
- History of in-transit metastases within the last 6 months
- Prior therapy targeting BRAF and/or MEK
SCCHN-specific exclusion criteria:
• Nasopharyngeal cancer, unknown primary, nasal cavity or paranasal sinus carcinoma
Exclusion criteria applicable across cohorts:
In addition, patients meeting any of the following criteria must be excluded:
1. Currently participating in or has participated in a trial of an investigational
agent or has used an investigational device within 4 weeks of the first dose of
trial treatment Note: Patients who have entered the follow-up phase of an
investigational trial may participate as long as it has been 4 weeks after the last
dose of the previous investigational agent.
2. Any prior treatment for the tumor under study
3. Prior therapy for another tumor 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, OX40, CD137), and discontinued from that treatment due to a grade 3
or higher immune-related adverse event (irAE)
4. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
weeks prior to first dose of trial treatment
- Note: Patients must have recovered from all adverse events (AEs) due to
previous therapies (i.e., grade ≤1 at baseline). Patients with grade ≤2
neuropathy are eligible for the trial. Patients with endocrine-related AEs
grade ≤2 requiring treatment or hormone replacement are also eligible.
- Note: If the patient has had major surgery, the patient must have recovered
adequately from the procedure and/or complications from the surgery prior to
starting trial treatment.
5. Live or live-attenuated vaccine within 30 days prior to the first dose of trial
treatment. Note: Administration of inactivated vaccines, mRNA-based vaccines [e.g.,
COVID-19] and vector-based vaccines are allowed.
6. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment. Patients who are currently receiving steroids at a dose equivalent to <5
mg/day of prednisone do not need to discontinue steroids prior to enrollment.
Patients who require topical, ophthalmologic and inhalational steroids will not be
excluded from the trial. Patients with hypothyroidism stable on hormone replacement
or Sjögren's syndrome will not be excluded from the trial.
7. Additional malignancy that is progressing or requires active treatment. Exceptions
include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in
situ cervical cancer that has undergone potentially curative therapy.
8. History of an allogeneic tissue/solid organ transplant.
9. Active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Patients with type I diabetes mellitus; hypothyroidism only requiring
hormone replacement; skin disorders (such as vitiligo, psoriasis, or alopecia) not
requiring systemic treatment; or conditions not expected to recur in the absence of
an external trigger are permitted to enroll.
10. History of radiation pneumonitis
11. History of (non-infectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease
12. Active infection requiring systemic therapy
13. HIV-infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman
Disease
14. Has known active hepatitis B virus (HBV; defined as hepatitis B surface antigen
[HBsAg] reactive and/or detectable HBV DNA) or known active hepatitis C virus (HCV)
(defined as anti HCV Ab positive and detectable HCV ribonucleic acid [RNA]
[qualitative]) infection.
Note: Testing for hepatitis B and hepatitis C is not required unless
1. Known history of HBV or HCV infection
2. Mandated by local health authority. Patients with a history of hepatitis will
be screened using serology to confirm status.
15. History or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient to participate, in the opinion of the treating investigator
16. Psychiatric or substance abuse disorders that would interfere with the patient's
ability to cooperate with the trial requirements
17. Severe hypersensitivity (grade ≥3) to pembrolizumab and/or any of its excipients