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RecruitingLast updated: 29 November 2023

KEYNOTE-E40: This study is evaluating how safe and effective a new drug is when given in combination with immunotherapy in people with melanoma or squamous cell carcinoma of the head and neckPhase II, Multi-cohort Trial of Neoadjuvant and Post-surgery IO102-IO103 and Pembrolizumab in Patients With Selected Resectable Tumors

Clinical summary

Summary

This study is evaluating a new drug called IO102-IO103 when it is given in combination with immunotherapy (called pembrolizumab) as neoadjuvant and post-surgery treatment for people with melanoma or squamous cell carcinoma of the head and neck (SCCHN).

Eligible participants will be allocated into cohorts depending on whether they have cutaneous resectable Stage III melanoma (Cohort A) or Stage III or IVA resectble SCCHN of the oral cavity, oropharynx (HPV-negative), hypopharynx, or larynx.

Participants in both cohorts will receive neoadjuvant treatment (either 2-3 cycles) with the study drug IO102-IO103, which will be administered as an injection under the skin, and pembrolizumab, which will be given intravenously.

All participants will then have surgery to remove their cancer 1 to 3 weeks after the last dose of neoadjuvant treatment.

All participants will then receive post-surgery treatment with IO102-IO103 and pembrolizumab for a total of 15 cycles (up to 45 weeks).

Patients with melanoma and patients with SCCHN who do not require Standard Of Care (SOC) Radiation Therapy ± chemotherapy (cisplatin) will start post-surgery IO102-IO103 and pembrolizumab after adequate recovery from surgery (approximately 1 to 2 months; no more than 12 weeks).Patients with SCCHN who require postoperative SOC therapy after surgery will start post-surgery IO102-IO103 and pembrolizumab after adequate recovery from SOC therapy (approximately 1 to 2 months; no more than 12 weeks).

Cancer

Multi-Cancer Multi-Cancer

Age

People18+

Phase

II

Trial Acronym

KEYNOTE-E40

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

IO Biotech

Scientific Title

Phase II, Multi-cohort Trial of Neoadjuvant and Post-surgery IO102-IO103 and Pembrolizumab in Patients With Selected Resectable Tumors

Eligibility

Inclusion

Melanoma-specific 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.

Exclusion

Melanoma-specific exclusion criteria:

  • 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

Inclusion

  • Your cancer has not spread to other parts of the body.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You have previously been treated (or are currently being treated) on a clinical trial.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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