Evaluation of GLR2007 for Advanced Solid Tumors

An Open-Label, Multicenter, Phase 1b/2 Study to Establish Safety, Tolerability, and Optimal Dosing Strategy of GLR2007 in Subjects with Advanced Solid Tumors

Inclusion criteria

• For Part 1 (Dose Escalation): Participants with advanced solid tumors who are refractory or intolerant to therapies known to provide clinical benefit.

• For Part 1 (Dose Escalation): The participant must have histological or cytological evidence of cancer (a solid tumor) that is advanced and/or metastatic. Biopsy is allowed by protocol if no histology or cytology records are available.
• For Part 2 (Dose Expansion): The participant must have histological or cytological evidence of cancer that is advanced and/or metastatic.
• For Part 1 (Dose Escalation): The participant has measurable or non-measurable disease.
• For Part 2 (Dose Expansion): The participant has measurable disease.
• The participant has given written informed consent prior to all study-specific procedures.
• The participant has adequate hematologic, hepatic, and renal function.
• The participant has discontinued all prior cancer therapies (including chemotherapy, immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for radiotherapy and non-myelosuppressive agents, prior to receiving GLR2007, and has recovered from the acute effects of therapy (treatment related toxicity resolved to ≤Grade 1) except for residual alopecia.
• The participant is willing and able to make themselves available for the duration of the study and is willing and able to follow study procedures.
• The participant meets contraceptive requirements.
• The participant has an estimated life expectancy of ≥3 months.
• The participant agrees to minimize ultraviolet exposure and sunlight for the duration of their study participation.
• A diagnostic contrast-enhanced magnetic resonance imaging (MRI) of the brain must be performed within 28 days prior to registration. Contrast-enhanced computed tomography (CT) is acceptable if MRI is not possible.

Cohort-specific inclusion criteria Part 2 (Cohort A, NSCLC)

• Histologically or cytologically confirmed NSCLC.
• Participants must have received at least 1 line of standard therapy for metastatic disease, including platinum-based chemotherapy and an immune checkpoint inhibitor given together or as separate lines of therapy, unless participants are ineligible for or cannot tolerate such therapy.
• Participants with anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase ROS (ROS1), v-Raf murine sarcoma viral oncogene homolog B (BRAF), and neurotrophic receptor tyrosine kinase 1 (NTRK) aberrations must have received therapy directed at their molecular aberration in order to enroll on this study.

Part 2 (Cohort B, Brain metastases of breast or NSCLC origin)

• Histologically or cytologically confirmed NSCLC or breast cancer at primary site.
• Participants with inoperable brain metastases (prior radiation therapy and/or stereotactic radiosurgery is allowed). A neurosurgical consult is at the discretion of the investigator.
• Participants with brain metastases of NSCLC origin must have received at least 1 line of standard therapy for metastatic disease, including platinum-based chemotherapy and an immune checkpoint inhibitor given together or as separate lines of therapy, unless participants are ineligible for or cannot tolerate such therapy.
• Participants with ALK, EGFR, ROS1, BRAF, and NTRK aberrations must have received therapy directed at their molecular aberration in order to enroll on this study.
• Participants with brain metastases from breast cancer who have previously received CDK4/6 inhibitors.

Part 2 (Cohort C, GBM)

• Histologically confirmed diagnosis of a recurrent primary World Health Organization Grade IV malignant glioblastoma. Participants with recurrent disease whose diagnostic pathology confirmed glioblastoma will not need re-biopsy. Participants with prior low-grade glioma or anaplastic glioma are eligible if histologic assessment demonstrates transformation to GBM.
• First recurrence of GBM.
• Candidate for surgical partial or gross-total resection.
• Radiographic demonstration of disease progression by contrast-enhanced CT or MRI following prior therapy.
• At least 2 weeks between prior surgical resection and adequate wound healing.
• At least 12 weeks from prior radiotherapy unless there is either histopathologic confirmation of recurrent tumor or new enhancement on MRI outside of the treatment field.

Exclusion criteria

• The participant has a personal history of any of the following conditions: major surgical resection involving the stomach or small bowel recurrent, unexplained or cardiac-related syncopal episodes within the last 6 months or ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation).
• Any concurrent malignancies currently requiring treatment or for which treatment would be deemed necessary within 3 months of enrollment; prostate cancer with androgen deprivation therapy, basal cell cancer, and squamous cell cancers are allowed.
• The participant is pregnant or lactating.
• The participant is immunocompromised and known to be human immunodeficiency virus positive. The participant has an active bacterial, fungal, and/or known viral infection (for example, hepatitis B surface antigen or hepatitis C antibodies).

Cohort-specific exclusion criteria:

Part 2 (Cohort A, NSCLC): The participant has NSCLC with worsening symptoms within 14 days prior to receiving GLR2007.

Part 2 (Cohort B, Brain metastases of breast or NSCLC origin): The participant has CNS metastasis with worsening symptoms within 14 days prior to receiving GLR2007.

Part 2 (Cohort C, GBM): The participant has GBM with worsening symptoms within 14 days prior to receiving GLR2007.