Clinical Trial 19293

Cancer Type:
Interventions:Avelumab; MSB00100718C (Avelumab); VX15/2503

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Michael Shafique

Overview

Study Title

Phase 1b/2 Study Of VX15/2503 In Combination With Avelumab In Advanced Non-Small Cell Lung Cancer

Summary

The purpose of this study is to evaluate the safety and tolerability of IV administration of VX15/2503 in combination with a fixed dose of avelumab in patients with advanced non-small cell lung cancer. The dose escalation portion of the study will determine the maximum tolerated dose (MTD) of VX15/2503 administered in combination with avelumab.

Objective

Primary Objective (Dose Escalation Phase): 1. To evaluate the safety and tolerability of ascending doses of VX15/2503 Q2W in combination with avelumab 10mg/kg Q2W. The primary safety endpoint is the number of subjects with dose-limiting toxicities (DLT)s during the 21-day DLT evaluation period at each dose level. Primary Objective (Dose Expansion Phase): 2. To evaluate safety and tolerability of RP2D of VX15/2503 administered in combination with 10 mg/kg avelumab Q2W

Inclusion Criteria

  • Age > 18 years
  • Signed informed consent prior to the performance of any study-specific procedures, including fresh tumor biopsies.
  • Histologically or cytologically proven advanced (stage IIIB/IV) Non-small lung cancer (NSCLC) patients who are immunotherapy naïve.
  • Escalation Phase: Participants may be enrolled with ≤ 2 lines of prior systemic anti-cancer therapy (but no immunotherapy). Potential participants who have had no prior systemic anti-cancer therapy (i.e., first-line therapy) or declined first-line treatment are permitted in the Escalation Phase.
  • Expansion Phase: Initially, only immunotherapy naïve patients who have progressed on first-line cytotoxic chemotherapy or who have declined first-line treatment with cytotoxic chemotherapy will be enrolled. Patients with no prior systemic anti-cancer therapy (i.e., first line therapy) may be enrolled in a second cohort if approved by the Safety Monitoring Committee (SMC). Patients previously treated with systemic adjuvant therapy, other than immunotherapy for recurrent advanced NSCLC, are also eligible.
  • Measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Availability of archival or fresh tumor specimen that is suitable for analysis. Acceptable samples must have been acquired using core needle biopsy or excisional biopsy. Samples that were acquired using fine needle aspiration are not acceptable.
  • Tumor lesion accessible for biopsy after the start of treatment. (Note: this lesion should be separate from measurable lesions that will be used for response assessment.)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1.
  • Tumors lack activating epidermal growth factor receptor (EGFR) mutations or ALK rearrangement (no EGFR or ALK testing is required if a subject has a KRAS mutation or squamous cell histology).
  • Adequate bone marrow, renal and hepatic function based upon laboratory
  • Highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) for both males and females if the risk of conception exists.
  • Resolution of toxicity from prior anti-cancer therapy, to NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade 0 or 1, except for alopecia (may be enrolled if their toxicity is determined to be irreversible and will not put them at undue risk from study treatment, based on the Investigator's assessment).

  • Exclusion Criteria

  • Prior therapy with any antibody or drug targeting T-cell coregulatory proteins (immune checkpoints), such as PD-1, PD-L1, or cytotoxic T lymphocyte antigen-4.
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on Investigator's judgment are acceptable.
  • Concurrent anti-cancer treatment within 28 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative bone directed radiotherapy]; immune therapy, or cytokine therapy, except for erythropoietin.
  • Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy); or use of any investigational drug within 28 days before the start of trial treatment.
  • If receiving immunosuppressive agents (such as steroids) for any reason, should be tapered off these drugs before initiation of the trial treatment. Some exceptions apply.
  • Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years. Some exceptions apply.
  • Rapidly progressive disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status score ≥ 2.
  • Women who are pregnant or breastfeeding.
  • History of pneumonitis or other interstitial lung disease
  • Active or history of any autoimmune disease including colitis and inflammatory bowel disease (subjects with diabetes Type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies.
  • Vaccination within 4 weeks of the first dose of avelumab and while on study is prohibited except for administration of inactivated vaccines (e.g., inactivated influenza vaccines).
  • Significant acute or chronic infection
  • Central nervous system (CNS) malignancy, the known presence of untreated or symptomatic CNS metastases. Patients with treated brain metastasis must be stable and off steroids and anti-convulsants for at least 1 month prior to the start of study treatment. Patients with suspected brain metastases at Screening should have a CT/MRI of the brain prior to study entry.
  • A history of hypersensitivity to other humanized monoclonal antibodies.
  • Significant cardiovascular disease (New York Heart Association Class II or greater), myocardial infarction within the 6 months prior to study entry
  • Legal incapacity or limited legal capacity.
  • Current alcohol or drug abuse.
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Prior organ transplantation or allogeneic bone marrow transplantation.
  • Any uncontrolled medical condition (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject's tolerance of trial treatment or confound interpretation of study assessments.
  • Inability to comply with visit schedule or other protocol requirements.