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Clinical Trial 19746

Cancer Type: Thoracic
Interventions:Avelumab; M3814; MSB00100718C (Avelumab)

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

  • Michael Shafique

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Multicenter, Open-Label, Dose Escalation Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor M3814 in Combination with Avelumab with and without Palliative Radiotherapy in Participants with Selected Advanced Solid Tumors

Summary

Objective

Part A Primary To determine a safe, tolerable, RP2D and/or the MTD of M3814 when given in combination with avelumab. Secondary Safety - To evaluate the safety profile and tolerability of M3814 in combination with avelumab. Pharmacokinetics - To characterize the pharmacokinetics of M3814 and avelumab when given as combination therapy. Immunogenicity - To evaluate the immunogenicity of avelumab in combination with M3814. Efficacy - To evaluate the preliminary antitumor activity of M3814 when given in combination with avelumab in participants with locally advanced or advanced solid tumors. Part B Primary - To determine a safe, tolerable, RP2D and/or the MTD of M3814 when given in combination with avelumab and radiotherapy. Secondary Safety - To evaluate the safety profile and tolerability of M3814 in combination with avelumab and radiotherapy. Pharmacokinetics - To characterize the pharmacokinetics of M3814 and avelumab when given in combination with radiotherapy. Immunogenicity - To evaluate the immunogenicity of avelumab in combination with M3814 plus radiotherapy. Efficacy - To evaluate the preliminary antitumor activity of M3814 when given in combination with avelumab and radiotherapy in participants with locally advanced and advanced solid tumors

Inclusion Criteria

  • Part A (M3814 + avelumab): Participants must have histologically or cytologically proven advanced or metastatic solid tumors for which no standard therapy exists, standard therapy has failed, or participants are intolerant to or have rejected established therapy known to provide clinical benefit for their condition
  • Part B (M3814 + Radiotherapy [RT] + avelumab): histologically or cytologically proven advanced or metastatic solid tumors with primary tumors or metastatic tumor lesions in the lung for which no standard therapy exists, standard therapy has failed, or participants are intolerant to or have rejected established therapy known to provide benefit for their condition and are amenable to receive RT to the tumor in the lung
  • Part A and B: Measurable or evaluable disease according to RECIST v 1.1
  • Part A and B: Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 at study entry Demonstrate adequate organ function including bone marrow, liver and kidney based on blood tests within 28 days of first dose of study therapy)/ Have provided tissue from an archival tissue sample or newly obtained tissue sample
  • Part A and B: Female participants of childbearing potential should be willing to use a highly effective contraceptive method or be surgically sterile, or abstain from heterosexual activity for the course of the study through 90 days after the last dose of study medication
  • Part A and B: Male participants should agree to refrain from donating sperm and use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy
  • Part A and B: Be willing to provide informed consent for the trial
  • Other protocol defined inclusion criteria may apply

  • Exclusion Criteria

  • Participants who have received prior chemotherapy, hormonal anticancer therapy with the exception of luteinizing hormone-releasing hormone analogs, biologic therapy, or any other anticancer therapy within 4 weeks prior to the first dose of study treatments (6 weeks for nitrosoureas or mitomycin C)
  • Participants who have undergone major surgery for any reason, except diagnostic biopsy, within 4 weeks of the study intervention.
  • Participants with evidence of active or history of autoimmune disease that might deteriorate when receiving an immune-stimulatory agent
  • Participants with evidence of active central nervous system (CNS) metastases. Some exceptions apply.
  • Participants with severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year), psychiatric or substance abuse disorders; or laboratory abnormalities that might confound trial results, interfere with the patient's participation or is not in the best interest of the participant
  • Participants requiring systemic immunosuppressive treatment (such as steroids) for any reason who cannot be tapered off these drugs before start of study treatment. Some exceptions apply.
  • Participants with a history of human immunodeficiency virus (HIV), HIV 1/2 antibodies or known acquired immunodeficiency syndrome, Hepatitis B or Hepatitis C
  • Participants who have received a live vaccine within 30 days prior to the first dose of trial treatment
  • Participants with known prior severe hypersensitivity to any of the investigational products or any component in its formulations
  • Participants with evidence of additional malignancy within the last 5 years unless a complete remission without further recurrence was achieved at least 2 years prior to study entry and patients were deemed to have been cured with no additional therapy required or anticipated to be required. Patients with treated nonmelanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate may participate
  • Participants pretreated with immunotherapy who have, any history of toxicities with prior immunotherapy agents, including Grade 3/4 immune-related adverse events (irAEs); irreversible irAEs; Grade greater than or equals to (>=) 3 irAEs that did not respond to steroid rescue; or neurologic irAE with significant clinical sequelae
  • Participants with irAE requiring hormone replacement therapy (e.g., thyroxine, insulin, or physiologic dose of corticosteroid replacement therapy for adrenal or pituitary insufficiency) may participate as long as the endocrinopathy is well controlled and the participant is not otherwise symptomatic from hormone insufficiency
  • Physiologic corticosteroid dose is defined as >Participants who are pregnant / breastfeeding or expecting to conceive within the duration of the trial, starting with the screening visit through 90 days after the last dose
  • for Part B only: Participants who have confirmed esophagitis and in whom radiation planning target volume will include any portion of the esophagus, Participants in whom more than 10 percent (%) of the total esophagus might receive more than 15 Gy (50% of the prescribed RT dose)
  • Participants who have had previous radiotherapy to the same region as intended to be irradiated in this study within the past 12 months Participants who have had extensive previous radiotherapy on >= 30% of bone marrow reserve or prior bone marrow/stem cell transplantation within 5 years before study start
  • Other protocol defined exclusion criteria may apply