A Phase II Multi-Arm (basket) Trial Investigating the Safety and Efficacy of IO102-IO103 in Combination with Pembrolizumab, as First-line Treatment for Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC), Squamous Cell Carcinoma of Head and Neck (SCCHN), or Metastatic Urothelial Bladder Cancer (mUBC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Io Biotech ApS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 May 2022 → 29 Nov 2025

Decision date (initial)

2024-02-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511561-10-00

EudraCT number

2021-003026-69

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective is to investigate the efficacy of IO102-IO103 in combination with pembolizumab in the frontline treatment of each of the different metastatic solid tumor indications (NSCLC PD-L1 ≥50%, SCCHN PD-L1 CPS ≥20 , or mUBC CPS ≥10 with the intent to expand a specific arm if a significant clinically relevant signal is observed.

Secondary objectives 1

1. The secondary objective is to investigate the safety of IO102-IO103 in combination with pembrolizumab in each of the 3 disease indications.

Conditions and MedDRA coding

Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patients with histologically or cytologically confirmed: Metastatic NSCLC (adenocarcinoma) (Cohort A), who have not received prior systemic treatment for their metastatic disease and who have: •No known sensitizing genetic aberrations where there are approved therapies (such as ALK, ROS1, EGFR, BRAF V600E, MET skipping mutations, and RET mutations or rearrangements) or SCCHN (Cohort B) with no prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally advanced disease) and who have: •SCCHN considered incurable by local therapies. Tumors of nasopharyngeal origin (any histology) are excluded •Documented results of p16/HPV status for oropharyngeal cancer (per institution standard) or Metastatic UBC (Cohort C) with no prior therapy and not eligible for any platinum-containing chemotherapy: •Urothelial cancer of the renal pelvis, ureter, bladder or urethra (transitional cell and mixed transitional/non transitional cell histologies permitted but transitional cell histology must be the dominant histology) For all cohorts, any solitary metastases must be biopsied to confirm diagnosis of metastases from primary indication.
2. PD-L1 TPS or PD-L1 CPS (as confirmed prior to enrolment using the PD-L1 IHC DAKO 22C3 PharmDx assay, using local or central services): •Cohort A (NSCLC adenocarcinoma): PD-L1 TPS ≥50% •Cohort B (SCCHN): PD-L1 CPS ≥20; HPV +/- •Cohort C (mUBC): PD-L1 CPS ≥10
3. A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies: •Not a woman of childbearing potential (WOCBP) •A WOCBP who agrees to follow contraceptive guidance starting with the screening visit and through 120 days after last dose of pembrolizumab or 180 days after last dose of chemotherapy. Note: A WOCBP, i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Tubal ligation is not a method of permanent sterilisation. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial in accordance with International Conference on Harmonization Good Clinical Practice Guideline (ICH-GCP) and local legislation prior to admission to the trial.
5. At least 18 years of age on day of signing informed consent.
6. Have measurable disease per RECIST v. 1.1 as assessed by local site investigator/radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
7. 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.
8. Have an ECOG performance status of 0 to 1.
9. If participant received major surgery, they must have recovered adequately from the adverse events and/or complications from the intervention prior to starting trial treatment.
10. Have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of trial treatment. Adequate organ function as defined by: •Haematology: Absolute neutrophil count ≥1500/µL or ≥1.5 × 109/L, Platelets ≥100,000/µL or ≥100 × 109/L, Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L. Criteria must be met without packed red blood cell transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin (≥ approximately 3 months). •Renal: Creatinine ≤1.5 × upper limit of normal (ULN), or Measured or calculated creatinine clearance (CrCl) ≥50 mL/min for patients with creatinine levels >1.5 × institutional ULN; GFR can also be used in place of creatinine or CrCl •Hepatic: 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 (≤5 × ULN for patients with liver metastases), Alkaline phosphatase ≤2.5 × ULN •Endocrine: No uncontrolled endocrinopathies •Coagulation: International normalised ratio or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
11. Patients who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment initiation. Note: Patients should remain on anti-viral therapy throughout trial treatment and follow local guidelines for HBV anti-viral therapy after completion of trial treatment. Hepatitis B screening tests are not required unless: a. Known history of HBV infection b. As mandated by local health authority
12. Patients with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening. Note: Patients must have completed curative anti-viral therapy at least 4 weeks before treatment initiation. Hepatitis C screening tests are not required unless: a. Known history of HCV infection b. As mandated by local health authority

Exclusion criteria 24

1. Cohorts A, B, and C: A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Cohorts A, B, and C: Has received 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, OX 40, CD137) AND was discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE).
3. Cohorts A, B, and C: Has received prior systemic anti-cancer therapy in the first line setting for the participant’s metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of metastatic disease).
4. Cohorts A, B, and C: Has not recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy are eligible.
5. Cohorts A, B, and C: Has received any prior radiotherapy, with the exception of palliative radiotherapy to non-target lesions, within 2 weeks prior to the start of trial treatment or radiotherapy to the lung >30 Gy within 6 months of start of trial treatment. Participants must have recovered from all radiation-related adverse events and not have had radiation pneumonitis requiring corticosteroids.
6. Cohorts A, B, and C: Have a life expectancy of <3 months and/or rapidly progressing disease.
7. Cohorts A, B, and C: Have received a live or live attenuated vaccine within 30 days prior to the first dose of trial treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Administration of killed vaccines, mRNA based (e.g., covid-19) and vector based vaccines are allowed. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
8. Cohorts A, B, and C: Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
9. Cohorts A, B, and C: Has a diagnosis of immunodeficiency
10. Cohorts A, B, and C: Received any of the following medications or procedures within 2 weeks prior to first dose of trial treatment: chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy
11. Cohorts A, B, and C: Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
12. Cohorts A, B, and C: Has CNS metastases and/or carcinomatous meningitis. Participants in Cohort A (NSCLC) with previously treated brain metastases may participate provided they are clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment.
13. Cohorts A, B, and C: Has severe hypersensitivity (≥ Grade 3) to IO102 or IO103, pembrolizumab and/or any of their excipients.
14. Cohorts A, B, and C: Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
15. Cohorts A, B, and C: Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis/insterstitial lung disease.
16. Cohorts A, B, and C: Has an active infection requiring systemic therapy.
17. Cohorts A, B, and C: Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
18. Cohorts A, B, and C: Known adrenal insufficiency function (that is basal cortisol level <140nmol/L or <5 μg/dL).
19. Cohorts A, B, and C: Has known active Hepatitis B virus (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: No testing for Hepatitis B and Hepatitis C is required unless a. Known history of HBV or HCV infection b. Mandated by local health authority. Patients who have a history of hepatitis will be screened using serology to confirm status.
20. Cohorts A, B, and C: Has a 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.
21. Cohorts A, B, and C: Has known psychiatric or substance abuse disorders that would interfere with the patient’s ability to cooperate with the requirements of the trial.
22. Cohorts A, B, and C: Is pregnant or breastfeeding or expecting to conceive within the projected duration of the trial, starting with the screening visit through 180 days after last dose of trial treatment.
23. Cohorts A, B, and C: Has had an allogeneic tissue/solid organ transplant.
24. Cohorts A, B, and C: Has progressive disease (PD) within six months of completion of curatively intended systemic treatment for locoregionally advanced SCCHN.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall objective response rate (ORR) according to RECIST v. 1.1

Secondary endpoints 6

1. Progression-Free Survival (PFS) according to RECIST v. 1.1
2. Duration of response (DOR)
3. Complete response rate (CRR)
4. Disease control rate (DCR)
5. Time to response (TTR)
6. Safety

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Io Biotech ApS

Sponsor organisation

Io Biotech ApS

Address

Ole Maaloees Vej 3

City

Copenhagen N

Postcode

2200

Country

Denmark

Scientific contact point

Organisation

Io Biotech ApS

Contact name

Clinical Operations Team

Public contact point

Organisation

Io Biotech ApS

Contact name

Clinical Operations Team

Third parties 9

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications