Inclusion Criteria. 1. Must be 18 years or older at the screening visit.
2. Histologically proven GBM (as defined in 2021 WHO Classification of Tumors of the
Central Nervous System; Louis, Perry, et al. 2021) that has recurred or progressed,
and for which resection is not indicated.
3. Tumor must be located in the supratentorial or cerebellar region. Tumors with
infratentorial locations require consultation with the Sponsor/Medical Monitor to
confirm suitability for treatment.
4. Previous treatment with standard of care radiotherapy (RT) and temozolomide
(temozolomide required only if tumor has at least partial methylation of the
O6-methylguanine-DNA methyltransferase promoter). Temozolomide should be
administered concurrent with RT and adjuvantly for newly diagnosed disease unless
intolerant or ineligible for treatment.
5. No recurrence within 4 weeks of completion of RT, defined from the imaging
assessment immediately after completion of RT.
6. Up to two prior systemic treatments for recurrent or progressing disease.
7. If receiving corticosteroids, must be maintained on a stable or decreasing dosage of
steroids for at least 7 days prior to C1D1.
8. Karnofsky Performance Score (KPS) ≥ 70 assessed within 14 days of C1D1.
9. Must have adequate organ and marrow function as defined below:
- - Absolute neutrophil count ≥ 1.5 ×10⁹/L (1,500/μL), without the use of myeloid
growth factors (e.g., granulocyte-colony stimulating factor) within 7 days
prior to C1D1 for short acting growth factors and 14 days for long-acting
growth factors to meet eligibility.
- - Platelets ≥ 75 × 10⁹/L (100,000/μL), unsupported, defined as no platelet
transfusion within 7 days prior to C1D1.
- - Hemoglobin ≥ 9 g/dL maintained without the need for erythropoietin stimulating
agents; subjects that require transfusion or growth factors need to demonstrate
stable hemoglobin of ≥ 9 g/dL over at least a 7-day period immediately prior to
C1D1.
- - Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN), in
subjects with Gilbert syndrome, total bilirubin >1.5 ULN as long as direct
bilirubin is normal.
- - ALT (SGPT) < 3 x institutional ULN.
- - AST (SGOT) < 3 x institutional ULN.
- - Potassium ≥ lower limit of normal (LLN).
- - Serum total calcium (correct for serum albumin) or ionized calcium ≥ LLN.
- - Estimated creatinine clearance (CrCl) by the Cockcroft-Gault (C-G) equation or
measured ≥ 60 mL/min.
Actual body weight will be used for calculation of the
C-G equation. If estimated CrCl is abnormal, accurate measurement should be
obtained by 24-hour urine collection to measure CrCl.
10. All colony-forming growth factor(s) (i.e., filgrastim, sargramostim or
erythropoietin) must have been discontinued for at least 7 days prior to C1D1 or 14
days if pegylated (PEG) formulations were received.
11. Have a life expectancy of at least 12 weeks.
12. An understanding, ability, and willingness to fully comply with study procedures and
restrictions.
13. Ability to provide written, signed, and dated (personally or via a legally
authorized representative) informed consent at screening as applicable to
participate in the study.
14. Females of childbearing potential (FOCP) must have a negative serum pregnancy test
at screening. Subjects of childbearing or child-fathering potential must be willing
to use highly effective birth control during the entire study. Acceptable forms of
birth control include hormonal contraceptives (oral, depot, injectable, transdermal,
or intravaginal) or intrauterine device (IUD) for at least one week prior to study
treatment, condom and spermicidal or diaphragm and spermicidal. Other acceptable
forms of birth control include a) abstinence for subjects who are not sexually
active or b) if the subject is in a monogamous relationship with a partner who is
sterile (e.g., vasectomy performed at least 6 months prior to subject's first study
treatment). Subjects who become sexually active or begin to have relations with a
partner who is not sterile during the trial must agree to use an effective form of
birth control for the duration of the study. FOCP taking hormonal therapy must be on
treatment for at least 12 weeks prior to C1D1 and must not change their dosing
regimen during the study.
Exclusion Criteria.Target disease. 1. Tumor in the brainstem (not including fluid-attenuated inversion recover [FLAIR]
changes), or a diagnosis of gliomatosis cerebri (highly infiltrative T2 hyperintense
tumor with ill-defined margins encompassing at least three lobes of the brain).
Tumors with infratentorial locations require consultation with the Sponsor/Medical
Monitor to confirm suitability for treatment.
Concurrent or prior therapy. 2. Subjects who have not recovered to Grade 1 or baseline from AEs (CTCAE v 5.0, or
most current) related to prior anticancer therapy (excluding alopecia, lymphopenia,
peripheral neuropathy, and ototoxicity, which are excluded only if ≥ Grade 3).
3. Prior systemic anticancer treatment:
1. Chemotherapy, biologic therapy (i.e., small molecular inhibitors), monoclonal
antibodies, investigational agents) within 21 days or 5 half-lives (whichever
is shorter), prior to C1D1 or per below:
2. Nitrosoureas or bevacizumab within 2 weeks prior to C1D1. 3. If a subject is receiving an anti-PD-1 or anti-PD-L1 antibody on a shorter
frequency (i.e., every two weeks), then the subject is eligible if last dose
was within 2 weeks prior to C1D1.
4. Prior therapy such as interstitial brachytherapy, Gliadel® Wafers (carmustine
implants), laser interstitial thermal therapy (LITT), or Optune therapy, within 4
weeks prior to C1D1 or as long as there are any ongoing treatment-related CTCAE
Grade ≥2 AEs or intolerable side effects.
5. Radiation therapy within 4 weeks prior to C1D1.
6. Use of potentially phototoxic substances (e.g., St. John's wort, griseofulvin,
thiazide diuretics, sulfonylureas, phenothiazines, tetracyclines, sulfonamides,
quinolones, hypericin extracts, topical preparations containing ALA) within 24 hours
before and after SONALA-001 infusion.
7. Use of fish oil supplements within 24 hours of C1D1 is allowed if the subject's
clotting parameters fall within normal limits.
8. Use of blood thinning agents within 7 days prior to C1D1. Subjects whose medical
condition does not permit discontinuation of this therapy are excluded.
9. Prior major surgery within 3 weeks prior to C1D1. Major surgery is defined as any
significantly invasive procedure into a major body cavity (abdomen, cranium etc.)
and/or surgery requiring extensive recuperation (joint replacement). Please discuss
with the Sponsor/Medical Monitor if there are any questions.
Medical history and concurrent disease. 10. Diagnosis of porphyria.
11. Hypersensitivity to porphyrins.
12. Known history of allergy to gadolinium contrast agents.
13. Inability to undergo MRI (e.g., verify the model of the pacemaker for ability to be
used with MRI).
14. Malignant disease, other than that being treated in this study. Note: Subjects with
basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma
in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone
potentially curative therapy are not excluded. Other exceptions include malignancies
that were treated curatively and have not recurred within 2 years prior to C1D1 and
any malignancy considered indolent or that do not require therapy.
15. Significant acute deterioration in neurologic status within 7 days prior to C1D1, in
the opinion of the investigator, including but not limited to new onset seizures
and/or increasing doses of corticosteroids.
16. Uncontrolled concurrent illness including, but not limited to:
- - ongoing or active infection.
- - transfusion dependent thrombocytopenia or anemia that prevent meeting
hematological inclusion criteria.
- - psychiatric illness/social situations that would limit compliance with study
requirements.
17. Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormality.
18. Pregnancy or breastfeeding.
19. A known or underlying medical condition that, in the opinion of the investigator or
Sponsor, could make the administration of investigational drug/ study treatment
hazardous to the subject, or could adversely affect the ability of the subject to
comply with or tolerate the study.
20. Inability to participate in the opinion of the investigator, by being unwilling or
unable to return for required follow-up visits or to obtain follow-up studies to
assess toxicity to therapy or to adhere to study plan, procedures, and restrictions.
