Inclusion Criteria:
1. For Part 1 (Dose Escalation): Participants with advanced solid tumors who are
refractory or intolerant to therapies known to provide clinical benefit.
1. 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.
2. For Part 2 (Dose Expansion): The participant must have histological or
cytological evidence of cancer that is advanced and/or metastatic.
2. For Part 1 (Dose Escalation): The participant has measurable or non-measurable
disease.
3. For Part 2 (Dose Expansion): The participant has measurable disease.
4. The participant has given written informed consent prior to all study-specific
procedures.
5. The participant has adequate hematologic, hepatic, and renal function.
6. 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.
7. 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.
8. The participant meets contraceptive requirements.
9. The participant has an estimated life expectancy of ≥3 months.
10. The participant agrees to minimize ultraviolet exposure and sunlight for the
duration of their study participation.
11. 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)
1. Histologically or cytologically confirmed NSCLC.
2. 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.
3. 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)
1. Histologically or cytologically confirmed NSCLC or breast cancer at primary site.
2. Participants with inoperable brain metastases (prior radiation therapy and/or
stereotactic radiosurgery is allowed). A neurosurgical consult is at the discretion
of the investigator.
3. 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.
4. 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.
5. Participants with brain metastases from breast cancer who have previously received
CDK4/6 inhibitors.
Part 2 (Cohort C, GBM)
1. 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.
2. First recurrence of GBM.
3. Candidate for surgical partial or gross-total resection.
4. Radiographic demonstration of disease progression by contrast-enhanced CT or MRI
following prior therapy.
5. At least 2 weeks between prior surgical resection and adequate wound healing.
6. 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:
1. 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).
2. 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.
3. The participant is pregnant or lactating.
4. 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.
