A Safety and Antitumor Activity Trial of Immunoradiotherapy Combinations as a Treatment Option for Subjects With Metastatic Solid Tumors

Lead sponsor

Genmab is the lead sponsor of 67 studies on the registry; 14 are open to participants now.

Of its 23 completed or terminated interventional studies of FDA-regulated products, 12 (52%) have results posted.

Eligibility criteria

Study arms

• Experimental
  Radiotherapy + GEN1042

  Biological: GEN1042 · Radiation: Radiotherapy

• Experimental
  Radiotherapy + GEN1042 + Pembrolizumab

  Biological: GEN1042 · Drug: Pembrolizumab · Radiation: Radiotherapy

Interventions

• BiologicalGEN1042

  Intravenous

• DrugPembrolizumab

  Intravenous

• RadiationRadiotherapy

  Radiotherapy

Primary outcomes

1. Number of Participants With Dose Limiting Toxicities (DLTs)

   A DLT was defined as any grade 5 toxicity, treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1, febrile neutropenia grade 3 or grade 4, grade 3 thrombocytopenia associated with clinically significant bleeding, grade 4 thrombocytopenia of any duration, grade 4 anemia, any grade ≥3 non-hematologic clinical (non-laboratory) toxicity with exceptions per protocol, any grade 3 or grade 4 non-hematologic laboratory value if clinically significant medical intervention was required to treat the participant or the abnormality led to hospitalization, or the abnormality persisted for \>7 days, and the abnormality resulted in a drug-induced liver injury (DILI) as defined by Hy's Law. Toxicities were graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).

   Time frame: 21 days

Secondary outcomes

1. Objective Response Rate (ORR)

   ORR was defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) v1.1 as assessed by investigator. CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to \<10 millimeters (mm) in all pathological target and non-target lesions. PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

   Time frame: Up to approximately 2 years 5 months

2. Duration of Response (DOR)

   DOR was defined as the time from the onset date of response to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator.

   Time frame: Up to approximately 2 years 5 months

3. Disease Control Rate (DCR)

   DCR was defined as the percentage of participants with BOR of CR, PR, and stable disease (SD) according to RECIST v1.1 as assessed by investigator. CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to \<10 millimeters (mm) in all pathological target and non-target lesions. PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).

   Time frame: Up to approximately 2 years 5 months

4. Progression Free Survival (PFS)

   PFS was defined as the time from the date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator.

   Time frame: Up to approximately 2 years 5 months

5. Overall Survival (OS)

   OS was defined as the time from date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to date of death due to any cause.

   Time frame: Up to approximately 2 years 5 months

6. Number of Participants With Abscopal Response in Non-irradiated Target Lesions As Assessed by the Investigator

   An abscopal response described radiotherapy (RT)-induced immune-mediated tumor regression at sites distant to the irradiated field. For the purpose of this trial, an abscopal response was defined as a reduction of at least 30% in diameter of the best responding unirradiated target lesion. Data are reported for the number of participants with abscopal response in non-irradiated target lesions as assessed by the investigator.

   Time frame: Up to approximately 2 years 5 months

7. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

   An adverse event (AE) was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE was any AE that occurred or worsened after the first dose of trial treatment. A summary of all Serious Adverse Events and Other Adverse Events (non-serious) regardless of causality is located in the 'Reported Adverse Events' Section.

   Time frame: Up to approximately 2 years 5 months

8. Blood Concentration of GEN1042 Over Time

   Blood samples were collected for measurement of serum concentrations of GEN1042. Data are reported for Cycle (C)1 Day (D)1 pre-dose and end of infusion (EOI), C1D8, C1D15, C2D1 pre-dose and end of infusion, C2D8, C2D15, C3D1 pre-dose and end of infusion,C4D1 pre-dose and end of infusion,C4D8, C5D1 pre-dose and end of infusion, C7D1 pre-dose and end of infusion,C11D1 end of infusion,C12D1 end of infusion+2 hours,C15D1 end of infusion,C19D1 end of infusion,C23D1 end of infusion, End of Treatment (\~D487) and Safety Follow Up (\~D517). Cycles were 21 days in length.

   Time frame: At multiple timepoints (as described in the "Outcome Measure Description" field between Cycle 1 Day 1 up to Safety Follow Up [up to approximately Day 517]). Cycles were 21 days in length.

9. Number of Participants With Anti-drug Antibodies (ADAs)

   Venous blood samples were drawn for analysis of ADAs. Data are reported for the number of participants with an on-treatment ADA status of positive. For on-treatment results, a participant was considered ADA positive if either 1) ADA was negative at baseline and at least one on-treatment result was positive 2) positive at baseline and at least one positive on-treatment result with at least one titer higher than baseline.

   Time frame: Up to approximately 2 years 5 months

Baseline characteristics

Related links

• Results Summary in Plain Language ↗

Study documents

• Protocol and statistical analysis plan · Jul 25, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No