Metastatic Non-Small Cell Lung Cancer (NSCLC), Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN), Metastatic Urothelial Bladder Cancer (mUBC) MedDRA version: 22.0 Level: LLT Classification code 10082179 Term: Squamous cell carcinoma of head and neck metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10046722 Term: Urothelial carcinoma bladder stage IV System Organ Class: 100
Conditions
Interventions
Product Name: IO102-IO103 + Montanide ISA 51 VG Sterile
Pharmaceutical Form: Emulsion for injection
INN or Proposed INN: Not yet assigned
CAS Number: 2130836-27-8
Current Sponsor code: IO102, IDO LONG
Sponsors
IO Biotech ApS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with histologically or cytologically confirmed: Metastatic NSCLC (adenocarcinoma) (Arm 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 EGFR, KRAS G12C, BRAF V600E, MET skipping mutations, and RET mutations or rearrangements) or Metastatic SCCHN (Arm B) with no prior therapy and who have: • Histologically- or cytologically-confirmed recurrent (without metastases) or metastatic SCCHN considered incurable by local therapies. Tumors of nasophyngeal origin (any histology) are excluded • Documented results of HPV status for oropharyngeal cancer. or Metastatic UBC (Arm C) with no prior therapy and not eligible for any platinum-containing chemotherapy: • Advanced/unresectable (inoperable) or metastatic 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 arms, 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/central services): • Arm A (NSCLC): PD-L1 TPS = 50% • Arm B (SCCHN): PD-L1 CPS = 20; HPV +/- • Arm 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 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 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 a blood sample and 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 in the protocol. Specimens must be collected within 10 days prior to the start of trial treatment. 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
Exclusion criteria
Exclusion criteria: Arms A, B, and C: 1. A WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If at any time, a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 2. 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 other than for adjuvant or neoadjuvant treatment AND was discontinued from that treatment due to a Grade 3 or higher immune-related AE 3. 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. Participants must have recovered from all AEs due to previous therapies to = Grade 1 or baseline. Participants with = Grade 2 neuropathy are eligible 5. Has received prior radiotherapy to the lung >30 Gy within 6 months of start of trial treatment and have recovered from all radiation-related adverse events, not have require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system (CNS) disease 6. Have a life expectancy of <3 months and/or rapidly progressing disease 7. 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, 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 are live attenuated vaccines and are not allowed 8. 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 9. Has a diagnosis of immunodeficiency 10. 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. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years 12. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during trial screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment 13. Has severe hypersensitivity (= Grade 3) to IO102 or IO103, pembrolizumab and/or any of their excipients 14. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: The secondary objective is to investigate the safety of IO102-IO103 in combination with pembrolizumab in each of the 3 disease indications.;Primary end point(s): The primary endpoints are Objective Response Rate (ORR) according to RECIST v1.1 or Progression-Free Survival (PFS) Rate at 6 months after last patient started treatment as per investigator assessments, whichever is earliest.;Timepoint(s) of evaluation of this end point: ORR is based in accordance with RECIST v.1.1. Complete or partial response must be confirmed by a second evaluation carried out at least 4 weeks later. The endpoint of PFR will be analyzed either 6 months after the last patient started treatment or after the target ORR is achieved, whichever is earliest. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The Key secondary endpoints are the following: • Progression-free survival (PFS) • Duration of response (DOR) • Complete response rate (CRR) • Disease control rate (DCR) • Overall survival (OS) • Time to response (TTR) • Safety Safety secondary endpoint: • Incidence of participants with AEs [ Up to 3 years ] • Incidence of participants with SAEs [ Time Frame: Up to 3 years ] • Incidence of treatment-related AEs [ Time Frame: Up to 3 years ] • Incidence of treatment-related SAEs [ Time Frame: Up to 3years ] • Incidence of AEs causing discontinuation of trial treatment;Timepoint(s) of evaluation of this end point: Secondary end points will be assessed on an ongoing basis for up to 3 years. OS will evaluated at 6 monthly intervals after first dose. | — |
Countries
Spain, United Kingdom, United States
Contacts
Public ContactEdyta Niemczyk
Theradex (Europe) Ltd.
Outcome results
None listed