Save

Phase II Trial of Neoadjuvant and Adjuvant IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Resectable Tumors

PHASE2RECRUITING

Simpliy with AI

Study details:

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. Approximately 60 patients with melanoma or SCCHN will be included (approximately 15 for each indication). During the neoadjuvant period, patients in cohort A, cohort B and Cohort C (Arm A) will receive IO102-IO103 and pembrolizumab KEYTRUDA® Q3W.

Patients in Cohort C (Arm B) will receive pembrolizumab KEYTRUDA® Patients with melanoma will receive 3 doses of neoadjuvant treatment. Patients with SCCHN will receive 2 or 3 doses of neoadjuvant treatment, at the investigator's discretion. Surgical resection will be performed 1 to 3 weeks after the last dose of neoadjuvant treatment.

All patients in cohort A,B and Cohort C (Arm A)will receive post-surgery treatment with IO102-IO103 and pembrolizumab KEYTRUDA® for a total of 15 cycles (up to 45 weeks). Patients in Cohort C (Arm B) will receive post-surgery treatment with pembrolizumab KEYTRUDA® for a total of 15 cycles (up to 45 weeks). Patients with melanoma and patients with SCCHN who do not require SOC RT ± cisplatin will start post-surgery treatment 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 KEYTRUDA® after adequate recovery from SOC therapy (approximately 1 to 2 months; no more than 12 weeks). Objective response will be based on imaging; pathologic tumor response of the surgical specimens will be assessed at the time of surgery. Safety will be assessed by recording adverse events.

The primary endpoint will be the percentage of patients with major pathologic response (MPR) in the resected tumor tissue after neoadjuvant treatment. Secondary endpoints include disease-free survival (DFS) at 2 years after surgery. All patients will have an end-of-treatment visit approximately 4 weeks after their last dose of trial treatment.

Follow-up visits will be conducted at 6 and 12 months after the end-of-treatment visit. Following completion of the 12-month follow-up period, long-term follow-up for overall survival (OS) will be conducted every 6 months for at least a further 12 month.

Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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.

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:

Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

Candidate for surgical resection with curative intent

The patient (or legally acceptable representative if applicable) provides written informed consent for the trial.

Age ≥18 years on the day of signing the informed consent form

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.

Eastern Cooperative Oncology Group (ECOG) performance score status of 0 or 1

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

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.

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

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)

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.

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 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

Nasopharyngeal cancer, unknown primary, nasal cavity or paranasal sinus carcinoma

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.

Any prior treatment for the tumor under study

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)

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.

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.

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.

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.

History of an allogeneic tissue/solid organ transplant.

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.

History of radiation pneumonitis

History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

Active infection requiring systemic therapy

HIV-infected patients with a history of Kaposi sarcoma and/or Multicentric Castleman Disease

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 known history of HBV or HCV infection, Mandated by local health authority. Patients with a history of hepatitis will be screened using serology to confirm status.

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

Psychiatric or substance abuse disorders that would interfere with the patient's ability to cooperate with the trial requirements

Severe hypersensitivity (grade ≥3) to pembrolizumab and/or any of its excipients

Simplify with AI

Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2023-12-21

Primary completion: 2025-04-30

Study completion finish: 2027-01-01

Study type

TREATMENT

Phase

PHASE2

Trial ID

NCT05280314

Intervention or treatment

DRUG: IO102-IO103

DRUG: Pembrolizumab KEYTRUDA®

Conditions

• Melanoma
• Squamous Cell Carcinoma of Head and Neck

Condition: Melanoma, Squamous Cell Carcinoma of Head and Neck
DRUG: IO102-IO103 and other drugs
Sydney, New South Wales, Australia and more
Sponsor: IO Biotech

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Melanoma Institute Australia The Uiniversity of Sydney, and Royal North Shore Hospital

Research sites nearby

Select from list below to view details:

Melanoma Institute Australia The Uiniversity of Sydney, and Royal North Shore Hospital
Sydney, New South Wales, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Cohort A - Melanoma Cutaneous resectable Stage III melanoma. Neoadjuvant Treatment (3 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W. Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W.	DRUG: IO102-IO103 IO102-IO103 is a combination of an indoleamine 2,3-dioxygenase 1 (IDO1) peptide (IO102) and a programmed death-ligand 1 (PD-L1) peptide (IO103), emulsified with an adjuvant (Montanide ISA 51 VG).
EXPERIMENTAL: Cohort B - SCCHN Stage III or IVA resectable locoregionally advanced Squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx (HPV-negative), hypopharynx, or larynx Neoadjuvant Treatment (2-3 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W.	DRUG: IO102-IO103 IO102-IO103 is a combination of an indoleamine 2,3-dioxygenase 1 (IDO1) peptide (IO102) and a programmed death-ligand 1 (PD-L1) peptide (IO103), emulsified with an adjuvant (Montanide ISA 51 VG).
EXPERIMENTAL: Cohort C Cutaneous resectable Stage III melanoma. Neoadjuvant Treatment (3 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W (Arm A) versus intravenous Pembrolizumab KEYTRUDA® 200mg Q3W alone (Arm B) Post-surgery Treatment (15 cycles): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) and intravenous Pembrolizumab KEYTRUDA® 200mg Q3W (Arm A) versus Pembrolizumab KEYTRUDA® 200mg Q3W alone (Arm B)	DRUG: IO102-IO103 IO102-IO103 is a combination of an indoleamine 2,3-dioxygenase 1 (IDO1) peptide (IO102) and a programmed death-ligand 1 (PD-L1) peptide (IO103), emulsified with an adjuvant (Montanide ISA 51 VG).

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Major pathologic response	Major pathologic response, defined as pathologic complete response (pCR) (0% residual viable tumor) or near pCR (≤10% residual viable tumor)	Observed in the resected tumor tissue after neoadjuvant treatment at surgery

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Pathologic complete response	Pathologic complete response (pCR) (0% residual viable tumor)	Observed in the resected tumor tissue after neoadjuvant treatment at surgery
Pathologic tumor response	Pathologic tumor response (≤ 49% residual viable tumor) at surgery	Pathologic tumor response of the surgical specimens will be assessed at the time of surgery.
Objective response rate	Objective response rate (ORR), determined by RECIST 1.1	Determined after 9 weeks of treatment
Disease-free survival	Disease-free survival (DFS) from the date of surgery	at 2 years after surgery
Event-free survival	Event-free-survival (EFS)	Determined after 9 weeks of treatment
Event-free survival	Event-free-survival (EFS)	at 2 years after surgery

Frequently Asked Questions

Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

No questions submitted. Be the first to ask a question!

You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

Clinical Trials Gov: Phase II Trial of Neoadjuvant and Adjuvant IO102-IO103 and Pembrolizumab KEYTRUDA® in Patients With Resectable Tumors