First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of GEN1047 in subjects with malignant solid tumors

Criteria - Escalation Part:

• Participant must have histologically or cytologically confirmed solid tumor(s) in any of the following selected indications for which there is no further available standard therapy likely to confer clinical benefit (or participant is not a candidate or has previously refused such earlier available therapy), and for whom, in the opinion of the investigator, experimental therapy with GEN1047 may be beneficial (breast cancer, endometrial cancer, ovarian cancer, squamous non-small-cell lung cancer [NSCLC-SCC]).
• Participants with ovarian cancer must have documented progressive disease (PD) on or after last prior treatment and within 60 days of screening.
• Must be at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) on the day of signing informed consent.
• Must have either recurrence after, or progression on or lack of response to available relevant standard of care (SoC) anticancer therapies; or are deemed intolerant to or ineligible for, standard curative therapy in the recurrent setting.
• Must have at least 1 measurable lesion per RECIST v1.1. The measurable lesion(s) must be outside the field of radiation therapy (RT) if there was prior treatment with RT.
• Must have an Eastern Cooperative Oncology Group performance status (ECOGPS) score of 0 to 1 at Screening and on C1D1 pretreatment.
• Should provide a tumor tissue sample during the Screening period and prior to C1D1.
• Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.

Criteria - Expansion Part:

• Participants must have documented PD according to RECIST v1.1 on or after last prior treatment with latest scan performed a maximum of 28 days prior to the first dose.
• Participant must have advanced (unresectable) or metastatic, histologically confirmed diagnosis (breast cancer, endometrial cancer, ovarian cancer.
• Must be a female and at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) at the time of consent.
• Must have at least 1 measurable lesion per RECIST v1.1 as assessed by local investigator.
• Must have an ECOG- PS score of 0 to 1 at Screening and on Cycle 1 Day 1 (C1D1) pretreatment.
• Should provide a tumor tissue sample during the Screening period and prior to C1D1.
• Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.

• Significant cardiovascular impairment within 6 months of the first dose of trial drug.
• Participant with new or progressive brain metastases or spinal cord compression.
• Participant has a history of bowel obstruction related to underlying disease.
• Participant has been exposed to any prior therapy with a compound targeting CD3 and/or B7H4 or cell based therapies.
• Current pneumonitis (any grade) including any radiological change of ongoing pneumonitis at baseline or history of non-infectious drug-, immune-, or radiation-related pneumonitis that required steroid.