Phase II Trial of Neoadjuvant and Adjuvant IO102-IO103 and Pembrolizumab in Patients With Resectable Tumors
Study Details
Study Description
Brief Summary
This is a multicenter, multi-arm trial evaluating anti-tumor activity, safety, and immune infiltration of IO102-IO103 in combination with pembrolizumab as neoadjuvant and adjuvant treatment. This proof-of-concept trial will include patients with resectable tumors in at least 2 indications.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is a multicenter, multi-arm trial evaluating anti-tumor activity, safety, and immune infiltration of IO102-IO103 in combination with pembrolizumab as neoadjuvant and adjuvant treatment.This proof-of-concept trial will include patients with resectable tumors in at least 2 indications. Eligible patients will be scheduled for surgery, such that neoadjuvant treatment can start 6 weeks before the planned date of surgery. During the neoadjuvant period, patients will receive IO102-IO103 weekly (6 doses) and pembrolizumab every 3 weeks (Q3W) (2 doses). After recovery from surgery, patients may receive risk-based post-operative standard of care (SOC) therapy, i.e., observation, radiotherapy, and/or chemotherapy. Patients who receive SOC chemotherapy/radiotherapy will start adjuvant IO102-IO103 and pembrolizumab after adequate recovery from SOC therapy. Patients who do not require SOC chemotherapy/radiotherapy will start adjuvant IO102-IO103 and pembrolizumab after adequate recovery from surgery. Each recovery period (after surgery or after SOC) is expected to be 1 to 2 months, but should be no more than 13 weeks. All patients will receive adjuvant treatment with IO102-IO103 and pembrolizumab for 12 months. 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 a further 2 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A - Melanoma Cutaneous resectable Stage IIIB, IIIC, or IIID melanoma or oligometastatic IV melanoma. Neoadjuvant Treatment (6 weeks): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) weekly, and intravenous Pembrolizumab 200mg Q3W × 2. Adjuvant Treatment (12 months): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) every 3 weeks (Q3W) for the first 18 weeks, followed by every 6 weeks (Q6W), and intravenous Pembrolizumab 400mg Q6W. |
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).
Drug: Pembrolizumab
Pembrolizumab administered intravenously
|
| Experimental: Cohort B - SCCHN Squamous cell carcinoma of the head and neck (SCCHN) in the oral cavity, oropharynx, hypopharynx, or larynx, HPV+/-, T1N1-N2b or T2-4N0-N2b. Neoadjuvant Treatment (6 weeks): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) weekly, and intravenous Pembrolizumab 200mg Q3W × 2. Adjuvant Treatment (12 months): Subcutaneous IO102-IO103 (IO102 85 μg and IO103 85 μg) every 3 weeks (Q3W) for the first 18 weeks, followed by every 6 weeks (Q6W), and intravenous Pembrolizumab 400mg Q6W. |
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).
Drug: Pembrolizumab
Pembrolizumab administered intravenously
|
Outcome Measures
Primary Outcome Measures
- Major pathologic response [Observed in the resected tumor tissue after neoadjuvant treatment at surgery]
Major pathologic response, defined as pathologic complete response (pCR) (0% residual viable tumor) or near pCR (≤10% residual viable tumor)
Secondary Outcome Measures
- Pathologic complete response [Observed in the resected tumor tissue after neoadjuvant treatment at surgery]
Pathologic complete response (pCR) (0% residual viable tumor)
- Pathologic tumor response [Pathologic tumor response of the surgical specimens will be assessed at the time of surgery.]
Pathologic tumor response (≤ 50% residual viable tumor) at surgery
- Objective response rate [Determined after 6 weeks of treatment]
Objective response rate (ORR), determined by RECIST 1.1
- Disease-free survival [at 2 years after surgery]
Disease-free survival (DFS) from the date of surgery
- Overall survival [Long-term follow-up for overall survival will be conducted every 6 months for a further 2 years.]
Overall survival (OS) from the date of surgery
- Adverse events [AEs will be collected from the time that the patient provides written informed consent until the end of the follow-up period of 12 months.]
Collection of Adverse events (AE)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Measurable disease based on RECIST 1.1
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Candidate for surgical resection with curative intent
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Willing and able to provide written informed consent for the trial
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Age ≥18 years on the day of signing the informed consent form
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Willing for archival tissue to be submitted for analysis
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Willing to undergo tumor biopsies (core, punch, incisional or excisional) before and during trial treatment
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Willing to undergo dwMRI (if available)
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Willing to undergo PD-L1 status evaluation
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ECOG performance score status of 0 or 1
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Adequate organ function performed on screening labs obtained within 4 weeks before first dose.
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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.
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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.
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Patients who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to start of trial intervention.
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Patients with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
Exclusion Criteria:
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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.
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Any prior treatment for the tumor under study
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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, OX40, CD137), and discontinued from that treatment due to a grade 3 or higher irAE
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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 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.
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Live or live-attenuated vaccine within 30 days prior to first dose of trial treatment. Note: Administration of inactivated vaccines, mRNA-based vaccines [e.g.,COVID-19] and vector-based vaccines are allowed.
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Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to first dose of trial treatment. Patients who are currently receiving steroids at a dose equivalent to >10mg/day of hydrocortisone or >5mg/day of prednisone equivalent 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 Sjogren's syndrome will not be excluded from the trial.
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Active (i.e., symptomatic or growing) CNS metastases
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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.
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History of an allogeneic tissue/solid organ transplant
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Active autoimmune disease that has required systemic treatment in the 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.
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History or current evidence of non-infectious pneumonitis/ interstitial lung disease that required steroids.
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Active infection requiring systemic therapy.
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History of HIV infection.
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Has known active HBV(defined as HBsAg reactive and/or detectable HBV DNA) or known active HCV(defined as anti HCV Ab positive and detectable HCV RNA [qualitative]) infection.
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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.
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Psychiatric or substance abuse disorders that would interfere with the patient's ability to cooperate with the trial requirements.
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Severe hypersensitivity (grade ≥3) to pembrolizumab and/or any of its excipients.
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Women of childbearing potential:Pregnant or breastfeeding, or expecting to conceive a child within the projected duration of the trial, from time of informed consent until at least 120 days after the last dose of trial treatment.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- IO Biotech
- Theradex
- Almac
Investigators
- Principal Investigator: Barbara Burtness, MD, Prof, Yale New Haven Hospital - Yale Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IO102-IO103-032