2023-08-23T00:00:00.000+10:00
Ongoing

STARSTRUCK 177Lu-TLX250-001

STARSTRUCK 177Lu-TLX250-001
Solid Tumors

A Phase 1b Dose Escalation/Expansion Study of the Combination of 177Lu-TLX250 and Peposertib in Patients with Carbonic Anhydrase IX (CAIX)-Expressing Solid Tumors

A Phase 1b Dose Escalation/Expansion Study of the Combination of 177Lu-TLX250 and Peposertib in Patients with Carbonic Anhydrase IX (CAIX)-Expressing Solid Tumors

Trial overview

Topic

Solid tumors

Eligibility criteria

Inclusion Criteria:

1.

a. Part 1 & Part 2 / Cohort B: Participants must have histologically confirmed advanced or metastatic solid tumor that has progressed on or during/after recognized standard of care therapies and are not eligible for resection, or patients that are not eligible or not consenting to recognized standard of care therapies. Cohort B: Excluding RCC of any histology.

 

b. Part 2 / Cohort A: Participants must have histologically confirmed advanced or metastatic ccRCC and must have received at least one prior line of systemic anticancer therapy in the advanced and/or metastatic setting, including at least one immune-checkpoint inhibitor or one tyrosine-kinase-inhibitor.

2.

a. At least one measurable lesion on CT/MRI according to RECIST 1.1 with corresponding 89Zr-TLX250 uptake (i.e., CAIX positive).

b. CAIX positivity in at least 75% of the total lesion volume (defined as 89Zr-TLX250 uptake with intensity significantly greater than normal liver [ie, standardized uptake value [SUV]max at least 1.5 times SUV of normal liver]).

Note: Solid tumors that are known to have high expression of CAIX include (but not exclusively) clear cell renal cell carcinoma (ccRCC), liver metastatic colorectal cancer (CRC), nasopharyngeal carcinoma (NPC), hepatocellular carcinoma (HCC), platinum-resistant/refractory epithelial ovarian carcinoma (EOC), leiomyosarcoma, small cell lung cancer (SCLC) and metastatic triple negative breast cancer (mTNBC).

3. Age ≥ 18 years at time of Screening.

4. ECOG status 0 or 1.

5. Have adequate organ function during Screening:

Bone marrow:

a. Leukocytes ≥ 3,000/µL

b. Absolute neutrophil count ≥ 1500/µL (administration of G-CSF is not allowed within 4 weeks prior to C1D1)

c. Platelets ≥ 100,000/µL (platelet transfusion is not allowed within 4 weeks prior to C1D1)

d. Haemoglobin ≥ 9g/dL (RBC transfusion is not allowed within 2 weeks prior to C1D1)

Liver function:

e. Total bilirubin ≤ 1.5 × the upper limit of normal (ULN). For patients with known Gilbert’s Syndrome ≤ 3 × ULN is permitted

f. Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5.0 × ULN for patients with hepatobiliary tumors or liver metastases

g. Albumin ≥ 2.8 g/L

h. International normalized ratio (INR) or prothrombin time (PT); AND activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN

i. For patients with hepatobiliary tumors or liver metastases, < 50% of the liver must be involved and patients must have a Child-Pugh class A or B7 liver score within 7 days of the first planned dose of study therapy

j. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

k. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Renal function:

 l. Serum/plasma creatinine ≤ 1.5×ULN or creatinine clearance ≥ 45 mL/min as measured by Cockroft-Gault formula or directly calculated by 24h urine.

6. Have the capacity to understand the study and be able and willing to comply with all protocol requirements.

7. Have the ability to receive and maintain oral medication.

8. Must comply with the radiation protection guidelines (including hospital admissions and isolation) that are applied by the treating institution in order to protect their contacts and the general public.

9. Must have a life expectancy of at least 6 months.

10. Females of childbearing potential must have a negative serum pregnancy test before study entry. Females of non-childbearing potential will have had at least 24 continuous months of natural (spontaneous) amenorrhea, and an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms), or have had hysterectomy, bilateral salpingectomy, or bilateral oophorectomy >6 weeks before screening.

11. Male or female patients: Male patients with female partners of childbearing potential and female patients of childbearing potential should agree to and are required to use highly effective contraception, during their participation in the study and for 6 months after the last administration of 89Zr-TLX250, 177Lu-TLX250 or peposertib, whichever is longer.

12. Male patients must also refrain from donating sperm during their participation in the study.

 

Exclusion Criteria

If an individual meets any of the following criteria, he/she is ineligible for this study:

 1. Inability to undergo CT or MRI; and PET imaging.

2. Prior 177Lu-TLX250 or other radioligand therapy; or any prior CAIX-targeting therapy.

3. Known hypersensitivity to compounds of similar chemical or biologic composition to peposertib, girentuximab, DFO or DOTA linker, zirconium or lutetium, any excipient in the study drug or any other intravenously administered human proteins/peptides/antibodies.

4. Administration of any radionuclide within 10 half-lives of the radionuclide prior to signature of the ICF.

5. Patients who have had chemotherapy, definitive radiation, biological cancer therapy, or investigational agent/device within 28 days of first planned dose of study therapy.

6. Patients who had > 2 prior lines of cytotoxic chemotherapy or had Grade 4 neutropenia or Grade 3/Grade 4 thrombocytopenia (both of a duration of at least 48 hours) during the last line of therapy.

7. Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes CYP3A4/5, CYP2C9, and CYP2C19. Concomitant use of CYP3A4/5 substrates with a narrow therapeutic index are also excluded. Patients may confer with the study doctor to determine if alternative medications can be used.

8. Patients who cannot discontinue concomitant H2-blockers or proton-pump inhibitors (PPIs). Patients may confer with the investigator to determine if such medications can be discontinued. These must be discontinued ≥ 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate.

9. Patients who are receiving therapeutic doses of anticoagulation, including but not limited to low-molecular weight heparin in therapeutic dosing or platelet aggregation inhibitors.

10. Patients with ≥ 5 bone metastases and/or bulky (> 3cm in diameter) pelvic or femoral tumors, and/or metastases/tumor in the vertebral spine involving > 3 vertebrae.

11. Known brain metastases, unless these metastases have been treated and stabilised for at least 4 weeks, prior to enrolment in the study.

12. Bleeding disorders precluding catheterization or invasive procedures.

13. Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator.

14. Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g., risk of doing harm to self or others), or patients with active severe personality disorders.

15. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 3 weeks of administration of study treatment.

16. Pregnancy or intention to father a child during the study period and for 7 months after study treatment discontinuation.

17. Breastfeeding during the study period and for 2.5 months after study treatment discontinuation.

18. Presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.

19. History of or concurrent malignancy (other than RCC in Part 2 Cohort A or CAIX-positive solid tumor in Part 2 Cohort B) with a life expectancy of ≤ 2 years; or requirement of systemic anti-cancer therapy; or requirement of local therapy that would confound study results.

20. Serious, non-healing wound, ulcer, or bone fracture.

21. Requirement of concurrent use of other anti-cancer treatments or agents other than study drugs. Supportive care therapies are permitted.

22. Any recent live vaccination within 4 weeks prior to treatment or plan to receive live vaccination during the study. Approved or authorized COVID-19 vaccines are permitted

Study details

Primary Objective

  • To assess the safety and tolerability of 177Lu-TLX250 in combination with peposertib and to determine the Maximum Tolerated Combination (MTC) / Recommended Phase 2 Dose (RP2D) of 177Lu-TLX250 in combination with peposertib.

Secondary Objective

  • To assess the preliminary efficacy of 177Lu-TLX250 in combination with peposertib.
  • To assess the development of anti-drug antibodies (ADA) [Human Anti-Chimeric Antibody (HACA)] following 177Lu-TLX250 administration.
Location
Murdoch :::

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