Trial Title:
IO102-IO103 in Combination With Pembrolizumab as First-line Treatment for Patients With Metastatic NSCLC, SCCHN, or mUBC
NCT ID:
NCT05077709
Condition:
Lung Cancer Non Small Cell
Head and Neck Squamous Cell Carcinoma
Urothelial Carcinoma Bladder
Conditions: Official terms:
Carcinoma
Squamous Cell Carcinoma of Head and Neck
Urinary Bladder Neoplasms
Carcinoma, Non-Small-Cell Lung
Pembrolizumab
Conditions: Keywords:
NSCLC
SCCHN
mUCB
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
All participants receive IO102-IO103 for three different indications.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IO102-IO103 in combination with pembrolizumab
Description:
The experimental drug IO102-IO103 is for SC injection and consist of IDO and PD-L1
peptides
Arm group label:
Arm A (NSCLC)
Arm group label:
Arm B (SCCHN)
Arm group label:
Arm C (mUBC)
Summary:
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 or Neck (SCCHN), or
Metastatic Urothelial Bladder Cancer (mUBC)
Detailed description:
Naturally occurring IDO/PD-L1 specific T-cells recognize MHC-bound IDO/PD-L1 peptides,
and are able to eliminate IDO expressing or PD-L1 expressing immune regulatory cells and
cancer cells. Activation of IDO or PD-L1 specific T-cells through vaccination with the
IDO and PD-L1 peptides (IO102-IO103) will boost natural killing of cancer cells and
counteract immune regulatory mechanisms in the tumor microenvironment. Thus, IDO/PD-L1
specific T-cells may both directly support anti-cancer immunity by killing target T-cells
but also indirectly by releasing pro-inflammatory cytokines in the microenvironment to
boost additional anti-cancer immunity.
This is a non comparative, open label, unblinded, multi-arm (basket) trial of IO102-IO103
in combination with pembrolizumab in three indications: NSCLC, SCCHN or mUBC. The primary
objective of the trial is to investigate the efficacy of IO102-IO103 in combination with
pembrolizumab in the frontline treatment in each of the different metastatic solid tumour
indications with the intent to expand a specific arm if a clinically meaningful signal is
observed based on primary endpoint (dual target of either ORR or PFS by investigator
assessment according to RECIST v.1.1).
Approximately 90 patients will be enrolled and treated; approximately 30 patients in each
arm. All eligible patients will receive treatment for up to 2 years with IO102-IO103
(IO102 85μg and IO103 185μg) SC Q3W in combination with pembrolizumab IV 200mg Q3W.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with histologically or cytologically confirmed:
Metastatic NSCLC (Arm A), who have not received prior systemic treatment for their
metastatic disease and who have:
• no known sensitizing EGFR or ALK mutations.
or
Metastatic SCCHN (Arm B) with no prior therapy and who have:
• Histologically- or cytologically-confirmed recurrent or metastatic SCCHN
considered incurable by local therapies. Tumors of nasopharyngeal 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 cisplatin
therapy:
• 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)
All solitary metastases must be biopsied to confirm diagnosis of metastases from
primary indication
2. PD-L1 tumor expression or PD-L1 CPS (as confirmed prior to enrolment using the DAKO
22C3 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 male participant able to father a child must agree to use contraception starting
with the screening visit and through 120 days after last dose of pembrolizumab or
180 days after last dose of treatment with IO102-IO103.
4. 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.
5. 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.
6. At least 18 years of age on day of signing informed consent
7. 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.
8. 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 tissue blocks are preferred to slides.
9. Have an ECOG performance status of 0 to 1.
10. 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.
11. 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 x 109/L Platelets ≥ 100,000/µL or ≥ 100
x 109/L Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L • Renal: Creatinine ≤ 1.5 x ULN, or
Measured or calculated creatinine clearance (CrCl) ≥ 60 mL/min for patients with
creatinine levels > 1.5 x institutional ULN; GFR can also be used in place of
creatinine or CrCl • Hepatic: Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN
for patients with total bilirubin levels ≤3 x ULN AST and ALT ≤ 2.5 x ULN (≤ 5xULN
for patients with liver metastases) Alkaline Phosphatase ≤ 2.5 x ULN
• Endocrine: Thyroid stimulating hormone (TSH) within normal limits, or Total T3 is
within normal limits, or Free T3 and free T4 are within the normal limits
- Coagulation:
International normalised ratio, PT or aPTT ≤ 1.5 x ULN unless patient is receiving
anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended
use of anticoagulants
Exclusion Criteria:
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 (eg,
CTLA-4, OX 40, CD137) other than for adjuvant or neoadjuvant treatment AND was
discontinued from that treatment due to a Grade 3 or higher immune-related AE
(irAE).
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 (BCG), and typhoid vaccine. 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. Participation in or has participated in a trial of an investigational agent within
30 days prior to study entry or has used an investigational device within 6 months
prior to the first dose of trial treatment. Note: Participants who have entered the
follow-up phase of an investigational trial may participate as long as it has been 6
months after the last dose of the previous investigational agent.
9. Has a diagnosis of immunodeficiency10. Received any of the following medications or
procedures within 2 weeks prior to time of treatment initiation: Systemic or topical
corticosteroids at immunosuppressive doses > 10 mg/day of hydrocortisone or >
5mg/day of prednisone equivalent.
10. 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.
11. 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.
12. Has severe hypersensitivity (≥Grade 3) to IO102 or IO103, pembrolizumab and/or any
of their excipients.
13. 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.
14. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
15. Has an active infection requiring systemic therapy.
16. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing
is required unless mandated by local health authority.
17. Known adrenal insufficiency function (that is basal cortisol level < 140nmol/L or <
5 μg/dL).
18. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (HCV) (defined as HCV ribonucleic acid
[RNA] [qualitative] is detected) infection.
19. 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.
20. Has known psychiatric or substance abuse disorders that would interfere with
cooperating with the requirements of the trial.
21. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 180 days
after last dose of trial treatment.
22. Has had an allogenic tissue/solid organ transplant.
23. Has progressive disease (PD) within six months of completion of curatively intended
systemic treatment for locoregionally advanced SCCHN.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Facility:
Name:
UC Davis Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Facility:
Name:
University of California San Diego
Address:
City:
San Diego
Zip:
92093
Country:
United States
Facility:
Name:
Mid Florida Hematology and Oncology Center
Address:
City:
Orange City
Zip:
32763
Country:
United States
Facility:
Name:
Montefiore Medical Center
Address:
City:
Bronx
Zip:
10467
Country:
United States
Facility:
Name:
University of Toledo Medical Center
Address:
City:
Toledo
Zip:
43614
Country:
United States
Facility:
Name:
Oregon Health & Science University
Address:
City:
Portland
Zip:
97239
Country:
United States
Facility:
Name:
University of Pennsylvania
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Facility:
Name:
Virginia Cancer Specialists
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Facility:
Name:
Hospital Vall d'Hebron
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Facility:
Name:
Institut Català d'Oncologia (ICO) Badalona (Catalan Institute of Oncology)
Address:
City:
Barcelona
Zip:
08916
Country:
Spain
Facility:
Name:
Hospital Universitari de Girona Doctor Josep Trueta
Address:
City:
Girona
Zip:
17007
Country:
Spain
Facility:
Name:
Hospital Universitario Ramon y Cajal
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Facility:
Name:
Hospital Universitario Fundación Jiménez Díaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen de la Victoria
Address:
City:
Malaga
Zip:
29010
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen Macarena
Address:
City:
Sevilla
Zip:
41009
Country:
Spain
Facility:
Name:
Hospital Clínico Universitario de Valencia
Address:
City:
Valencia
Country:
Spain
Facility:
Name:
Hospital Clínico Lozano Blesa
Address:
City:
Zaragoza
Zip:
50009
Country:
Spain
Facility:
Name:
Velindre Cancer Center
Address:
City:
Cardiff
Zip:
CF14 2TL
Country:
United Kingdom
Facility:
Name:
Guys and St Thomas Hospital
Address:
City:
London
Country:
United Kingdom
Start date:
February 14, 2022
Completion date:
November 30, 2024
Lead sponsor:
Agency:
IO Biotech
Agency class:
Industry
Collaborator:
Agency:
Theradex
Agency class:
Industry
Collaborator:
Agency:
Almac
Agency class:
Industry
Collaborator:
Agency:
NeoGenomics
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
IO Biotech
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05077709
