IO102-IO103 + Pembrolizumab for Resectable Cancer

Recruiting at14 trial locations

Overseen by Barbara Burtness, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: IO Biotech

Must be taking: Antiretrovirals, Hepatitis B antivirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the trial treatments.

What data supports the effectiveness of the drug pembrolizumab (KEYTRUDA) for resectable cancer?

Pembrolizumab has shown promise in treating non-small cell lung cancer (NSCLC) when used before surgery, as well as in advanced NSCLC with high PD-L1 levels, and has been approved for use in certain colorectal cancers with specific genetic features, indicating its potential effectiveness in various cancers. ^{1 2 3 4 5}

Is the combination of IO102-IO103 and Pembrolizumab safe for humans?

Pembrolizumab (Keytruda) has been used in various clinical trials and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related reactions such as pneumonitis (lung inflammation) and thyroid disorders. These side effects have been observed in trials for different types of cancer, indicating that while the treatment is effective, it does carry some risks. ^{2 6 7 8 9}

How is the drug IO102-IO103 + Pembrolizumab unique for resectable cancer?

The combination of IO102-IO103 with Pembrolizumab is unique because it involves using an immune checkpoint inhibitor (Pembrolizumab) that blocks a pathway (PD-1/PD-L1) to help the immune system attack cancer cells, which has shown effectiveness in various cancers. This approach is novel for resectable cancers, as it combines a new treatment (IO102-IO103) with an established drug (Pembrolizumab) to potentially enhance the immune response before surgery. ^{2 3 8 10 11}

Research Team

Barbara Burtness, MD

Principal Investigator

Yale New Haven Hospital - Yale Cancer Center

Eligibility Criteria

This trial is for adults with certain types of resectable tumors, including oral squamous cell carcinoma and melanoma. Participants must be willing to provide tissue samples, undergo tumor biopsies and imaging tests, have a performance status score of 0 or 1 (which indicates they are fully active or restricted in physically strenuous activity but ambulatory), and have not undergone previous treatments for these conditions.

Inclusion Criteria

My recent tests show my organs are working well.

My cancer is in the mouth, throat, or voice box and can be surgically removed.

You possess measurable disease characteristics according to the Response Evaluation Criteria in Solid Tumors version 1.1.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive IO102-IO103 and pembrolizumab KEYTRUDA® as neoadjuvant treatment for 2-3 cycles

6-9 weeks

3 visits (in-person)

Surgery

Surgical resection is performed 1 to 3 weeks after the last dose of neoadjuvant treatment

1-3 weeks

Post-surgery Treatment

Participants receive post-surgery treatment with IO102-IO103 and pembrolizumab KEYTRUDA® for a total of 15 cycles

45 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up visits at 6 and 12 months after end-of-treatment visit

Long-term Follow-up

Long-term follow-up for overall survival conducted every 6 months for at least a further 12 months

12 months

Treatment Details

Interventions

• IO102-IO103 (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The trial is testing IO102-IO103 combined with pembrolizumab as both pre-surgery (neoadjuvant) and post-surgery (adjuvant) treatment. It aims to assess the anti-tumor effects, safety profile, and how this combination influences immune cells within the tumors across multiple centers.

Participant Groups

Group I: Cohort C Experimental Treatment 2 Interventions

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)

Group II: Cohort B - SCCHN Experimental Treatment 2 Interventions

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.

Group III: Cohort A - Melanoma Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

IO Biotech

Lead Sponsor

Trials

9

Recruited

750+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Almac

Industry Sponsor

Trials

4

Recruited

490+

Theradex

Industry Sponsor

Trials

34

Recruited

1,600+

Almac

Collaborator

Trials

4

Recruited

490+

Findings from Research

The Trial Reporting in Immuno-Oncology (TRIO) recommendations were developed by a diverse group of experts to enhance the reporting standards for clinical trials involving immuno-oncology treatments, focusing on their unique efficacy and toxicity profiles.

These recommendations aim to provide clearer evidence on the benefits and risks of immuno-oncology therapies, acknowledging that the field is rapidly evolving and will require ongoing updates to stay relevant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement. Tsimberidou, AM., Levit, LA., Schilsky, RL., et al.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a study of 243 patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, there was no significant difference in overall survival between those treated with pembrolizumab alone (IO-mono) and those receiving it in combination with chemotherapy (CT-IO), suggesting that avoiding chemotherapy does not negatively impact survival outcomes.

Younger patients and those with more severe symptoms or brain metastases were more likely to receive the combination treatment, but factors like male gender and poor performance status were identified as negative predictors for overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world multicentre cohort of first-line pembrolizumab alone or in combination with platinum-based chemotherapy in non-small cell lung cancer PD-L1 ≥ 50. Pons-Tostivint, E., Hulo, P., Guardiolle, V., et al.[2023]

Pembrolizumab (Keytruda) has been approved for treating metastatic microsatellite instability-high colorectal cancer (CRC), showing promising efficacy in a small phase 2 clinical trial, which highlights the potential of immunotherapy in this cancer type.

Microsatellite instability-high CRCs that express PD-L1 are more likely to respond to PD-1/PD-L1 checkpoint inhibitors, while microsatellite-stable tumors show much less response, indicating the importance of PD-1/PD-L1 testing in guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II-The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer. Marginean, EC., Melosky, B.[2022]

The Trial Reporting in Immuno-Oncology (TRIO) recommendations were developed by a diverse group of experts to enhance the reporting of clinical trials for immuno-oncology treatments, focusing on their unique efficacy and toxicity profiles.

These recommendations aim to provide clearer evidence on the benefits and risks of immuno-oncology therapies, acknowledging that they will need to be updated regularly as the field evolves and more data becomes available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Reporting in Immuno-Oncology (TRIO): an American society of clinical oncology-society for immunotherapy of cancer statement. Tsimberidou, AM., Levit, LA., Schilsky, RL., et al.[2019]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

A 70-year-old woman developed immune checkpoint inhibitor (ICI)-related myocarditis and new-onset myasthenia gravis (MG) after starting pembrolizumab for metastatic thymic cancer, highlighting potential serious side effects of this treatment.

Despite the adverse effects, the patient showed significant improvement in her metastatic disease after 6 weeks, indicating that pembrolizumab can be effective in reducing tumor burden even in the presence of severe immune-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. Szuchan, C., Elson, L., Alley, E., et al.[2022]

Pembrolizumab, an immune-checkpoint inhibitor, has shown the ability to achieve pathological complete response (CR) in a patient with microsatellite instability-high (MSI-H) colorectal cancer, marking a significant milestone in confirming its efficacy beyond clinical response.

In this case, a 45-year-old man with advanced colon cancer underwent 20 courses of pembrolizumab treatment, leading to no residual tumor cells after surgery, highlighting the importance of accurate diagnosis and monitoring for effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability. Tominaga, T., Nonaka, T., Fukuda, A., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement. [2020]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Real-world multicentre cohort of first-line pembrolizumab alone or in combination with platinum-based chemotherapy in non-small cell lung cancer PD-L1 ≥ 50. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II-The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Trial Reporting in Immuno-Oncology (TRIO): an American society of clinical oncology-society for immunotherapy of cancer statement. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor-induced myocarditis and myasthenia gravis in a recurrent/metastatic thymic carcinoma patient: a case report. [2022]

11. Japan pubmed.ncbi.nlm.nih.gov

Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability. [2022]