A Study of IMU-201 (PD1-Vaxx), a B-Cell Immunotherapy, in Adults with Non-Small Cell Lung Cancer

An Open Label, Multi-Center, Dose Escalation/Expansion, Phase 1/1b Study of IMU 201 (PD1-Vaxx), a B-Cell Immunotherapy as monotherapy or in combination with atezolizumab with or without chemotherapy, in Adults with Non-Small Cell Lung Cancer (IMPrinter).

Investigational Medicinal Product, IMU-201, consists of drug substance, APi2568, which is a B-cell epitope (amino acids 92-110 from PD-1) linked to a promiscuous T-cell epitope (amino acid residues 288-302 from measles virus fusion protein) via a 4-amino acid linker (Gly-Pro-Ser-Leu), and combined with Water for Injection (WFI) forms the drug product, IMU-201, which becomes PD1-Vaxx when emulsified with excipient Montanide ISA 720 VG.

It is hypothesized that a polyclonal induced B-cell antibody response will be more effective or as effective with improved safety over current monoclonal antibody therapy.

This phase 1/1b study is an open-label dose escalation/dose expansion study designed to assess the safety, tolerability, immunogenicity and efficacy of IMU-201 (PD1-Vaxx). Phase 1 monotherapy dose-escalation of IMU-201 (PD1-Vaxx), will enroll approximately 9-18 patients and establish the optimal monotherapy biological dose (mBOD). Once established, the dose cohort will be expanded to enroll additional 10 patients at the mBOD dose level. Phase 1b, a combination dose-escalation of IMU-201 (PD1-Vaxx) with atezolizumab and with or without chemotherapy, will enroll approximately 18-36 patients and establish the optimal combotherapy biological dose (cBOD). Once established, the dose cohort will be expanded to enroll additional 30 patients at the cBOD dose level.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥ 18 years with histologically confirmed non-small-cell lung cancer (NSCLC) tumor stage IIIb not eligible for definitive treatment or stage IV
2. Prior treatment criterion for Monotherapy dose escalation and expansion: progressed on/after prior PD-1/PD-L1 containing regimen
3. Prior treatment criteria for Combination dose escalation arms:

   1. IMU-201 + atezolizumab, patients naïve to prior treatment or progressed on/after prior PD-1/PD-L1 containing regimen
   2. IMU-201 + atezolizumab + chemotherapy, patient naïve to prior treatment naive
4. Prior treatment criteria for Combination dose expansion arms:

   1. IMU-201 + atezolizumab, progressed on/after prior PD-1/PD-L1 containing regimen
   2. IMU-201 + atezolizumab, patients naïve to prior treatment
   3. IMU-201 + atezolizumab + chemotherapy, patients naïve to prior treatment
5. PD-L1 expression criteria (testing by 22C3, SP142, or SP263) for Monotherapy dose escalation and expansion: TPS/TC ≥ 50% or IC ≥ 10%. Patients with PD-L1 TPS/TC\<50% or IC\<10% expression may be included with agreement of Sponsor
6. PD-L1 expression criteria for Combination dose escalation arms:

   1. IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
   2. IMU-201 + atezolizumab + chemotherapy, independent of PD-L1 expression
7. PD-L1 expression criteria for Combination dose expansion arms:

   1. IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
   2. IMU-201 + atezolizumab, TPS/TC ≥ 50% or IC ≥ 10%
   3. IMU-201 + atezolizumab + chemotherapy, independent of PD-L1 expression
8. Life expectancy of at least 12 weeks in the opinion of the Investigator
9. Zubrod/ECOG score performance status 0-1
10. At least one measurable lesion as defined by RECIST 1.1 criteria.
11. Adequate hematologic, liver, and renal function

Exclusion Criteria:

1. Prior therapy for advanced NSCLC within 3 weeks prior to Day 1;
2. Continuous systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks prior to first dose of study treatment.;
3. Any previous grade 3 or higher toxicity to a PD-1 inhibitor or PD-L1 inhibitor;
4. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required treatment with immunosuppressive agents or has current pneumonitis/interstitial lung disease;
5. Known brain metastases requiring steroid treatment, or signs and symptoms indicating suspected brain metastases;
6. Current or previous history of auto-immune disease;
7. NSCLC expressing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), B-Raf proto-oncogene (BRAF) or ROS proto-oncogene 1 (ROS1) mutations who have not received appropriate therapies targeting these mutations and progress (if treatments are not available, patients who have NOT received appropriate therapies may be enrolled);
8. Prior organ transplant;
9. Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
10. History of uncontrolled seizures, central nervous disorders, or psychiatric disability judged by the Investigator to be clinically significant and precluding informed consent, participation in the study, or adversely affecting compliance to study drugs;
11. Active infection requiring intravenous antibiotics;
12. Known history of human immunodeficiency virus (HIV) infection or Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV Ribonucleic acid (RNA) \[qualitative\] is detected) infection;
13. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry;
14. Any vaccination within 2 weeks prior to starting study treatment;
15. Treatment with any investigational drug or participation in another investigational study within 3 weeks prior to first IMU-201 dose.