Study of Avelumab-M3814 Combinations

NCT ID: NCT03724890

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-27
• Study Completion Date: 2022-08-17

Brief Summary

The main purpose of the study was to evaluate a safe, tolerable recommended Phase II dose (RP2D) and/or the maximum tolerated dose (MTD) of M3814 when given in combination with avelumab with and without radiotherapy in participants with selected advanced solid tumors.

Conditions

Oncology; Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: M3814 + Avelumab

Group Type: EXPERIMENTAL

M3814

Intervention Type: DRUG

Participants received M3814 twice daily (BID) continuously starting from Day 1 until progressive disease (PD) or unacceptable toxicity.

Avelumab

Intervention Type: DRUG

Participants received avelumab once every 2 weeks (Q2W) starting from Day 1 until PD or unacceptable toxicity.

Part B: M3814 + Avelumab + Radiotherapy (RT)

Group Type: EXPERIMENTAL

M3814

Intervention Type: DRUG

Participants received M3814 concomitantly with RT once (QD) daily starting Day 1 for 5 days per week for 2 weeks in total.

Avelumab

Intervention Type: DRUG

Participants received avelumab once every 2 weeks (Q2W) starting from Day 1 until PD or unacceptable toxicity.

Radiotherapy

Intervention Type: RADIATION

Participants received radiotherapy at the dose of 3 grays (Gy) per day starting Day 1 for 5 days per week for 2 weeks.

Part FE: M3814 + Avelumab (fasted/fed state)

Group Type: EXPERIMENTAL

M3814

Intervention Type: DRUG

Participants received M3814 twice daily (BID) continuously starting from Day 1 until progressive disease (PD) or unacceptable toxicity.

Avelumab

Intervention Type: DRUG

Participants received avelumab once every 2 weeks (Q2W) starting from Day 1 until PD or unacceptable toxicity.

Interventions

M3814

Participants received M3814 twice daily (BID) continuously starting from Day 1 until progressive disease (PD) or unacceptable toxicity.

Intervention Type: DRUG

M3814

Participants received M3814 concomitantly with RT once (QD) daily starting Day 1 for 5 days per week for 2 weeks in total.

Intervention Type: DRUG

Avelumab

Participants received avelumab once every 2 weeks (Q2W) starting from Day 1 until PD or unacceptable toxicity.

Intervention Type: DRUG

Radiotherapy

Participants received radiotherapy at the dose of 3 grays (Gy) per day starting Day 1 for 5 days per week for 2 weeks.

Intervention Type: RADIATION

Other Intervention Names

Peposertib; MSC2490484A; Peposertib; MSC2490484A

Eligibility Criteria

Inclusion Criteria

• Part A and Part FE (M3814 + avelumab): Participants had 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 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
• Part A, B and FE: Measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1)
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 at study entry
• Part A, B and FE: Female participants of childbearing potential should be willing to use a highly effective contraceptive method
• Part A, B and FE: Male participants should agree to refrain from donating sperm plus, either: abstain from any activity that allows for exposure to ejaculate
• 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, B and FE: Be willing to provide informed consent for the trial

Exclusion Criteria

• Participants who had received prior chemotherapy, hormonal anticancer therapy with the exception of luteinizing hormone-releasing hormone analogs, biologic therapy, or any other anticancer therapy within 28 days of the first dose of study treatments (6 weeks for nitrosoureas or mitomycin C)
• Participants who had undergone major surgery for any reason, except diagnostic biopsy, within 4 weeks of the study intervention and/or has not fully recovered from the surgery 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 brain metastases, except those meeting the following criteria: a) brain metastases that have been treated locally and are clinically stable for greater than or equal to (>=) 4 weeks prior to randomization b) no ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) c) participants must be either off steroids or on a stable or decreasing dose of less than (<) 10 milligrams (mg) daily prednisone (or equivalent)
• 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 active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results
• Participants requiring systemic immunosuppressive agents (such as steroids) for any reason who cannot be tapered off these drugs before start of study intervention, with the following exceptions: a) participants with adrenal insufficiency, may continue corticosteroids at physiologic replacement dose, equivalent to less than or equal to (<=) 10 mg prednisone daily b) participants requiring steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) is permitted c) participants with previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon planned to be completed in 14 days, or that the dose after 14 days will be equivalent to <= 10 mg prednisone daily
• Participants with a history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome, Hepatitis B virus or Hepatitis C and with history of infection must have a polymerase chain reaction (PCR) documentation that infection is cleared
• Participants who had 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 participants were deemed to have been cured with no additional therapy required or anticipated to be required. Participants 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 dose limiting toxicities (DLTs) 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 <= 10 mg daily of prednisone or equivalent
• for Part B only:
• Participants who had confirmed esophagitis and in whom radiation planning target volume will include any portion of the esophagus, the participant is not eligible unless an esophageal endoscopy rules out the presence of esophagitis
• Participants in whom more than 10 percent (%) of the total esophagus volume might receive more than 15 gray (Gy) (50% of the prescribed radiotherapy [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 had had extensive previous radiotherapy on >= 30% of bone marrow reserve or prior bone marrow/stem cell transplantation within 5 years before study start
• If participant hepatic metastatic lesion is selected to be irradiated: - the non-tumor liver volume < 700 milli liters (mL); - Child-Pugh score >= 8

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

Mount Sinai - PRIME (10707)

Lake Success, New York, United States

UC Health Clinical Trials Office (10702)

Cincinnati, Ohio, United States

University of Oklahoma Health Sciences Center - Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, United States

Greenville Hospital System University Medical Center (ITOR)

Greenville, South Carolina, United States

Vanderbilt-Ingram Cancer Center (8867)

Nashville, Tennessee, United States

Countries

United States

References

Perez B, Aljumaily R, Marron TU, Shafique MR, Burris H, Iams WT, Chmura SJ, Luke JJ, Edenfield W, Sohal D, Liao X, Boesler C, Machl A, Seebeck J, Becker A, Guenther B, Rodriguez-Gutierrez A, Antonia SJ. Phase I study of peposertib and avelumab with or without palliative radiotherapy in patients with advanced solid tumors. ESMO Open. 2024 Feb;9(2):102217. doi: 10.1016/j.esmoop.2023.102217. Epub 2024 Feb 5.

Reference Type: BACKGROUND

PMID: 38320431 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201964_0001

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

MS201964_0001

Identifier Type: -

Identifier Source: org_study_id