Authorised Phase I and Phase II (Integrated)- First administration to humans Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation

The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a p53 Y220C Mutation (PYNNACLE)

EU CTIS ID: 2023-504251-27-00

What this study is testing

To evaluate the efficacy of rezatapopt per Blinded Independent Central Review (BICR) assessment.

Phase I and Phase II (Integrated)- First administration to humans

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Patient is at least 18 years of age.
10.Patients who are males and have a female partner of childbearing potential must (1) use a condom, both for contraception and to protect any existing pregnancy and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as described in inclusion criterion #9, or (2) agree to be abstinent from heterosexual intercourse as their preferred and usual lifestyle. These requirements should be followed starting with the first dose of study drug through 3 months after the last dose of study drug. Refer to Appendix 2 for contraceptive guidance.
11. Patients must be willing to undergo a tumor biopsy during screening for NGS if an archival tumor specimen is not available and if the procedure is in line with standard of care (i.e., of low risk to patient and the tumor is of sufficient size to be biopsied).
12. Patient has a life expectancy of at least 3 months as assessed by the Investigator.
13. Measurable disease per RECIST v1.1 as assessed by the Investigator, with the last imaging performed within 28 days before C1D1.
2. Patient understands the study procedures and agrees to participate by giving written, signed, and dated informed consent prior to any mandatory study-specific procedures, sampling, or analysis.

You likely can't join if

1. Patient has received prior chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent within 21 days or 5 half-lives (if half-life is known), whichever is shorter, before receiving their first dose of study drug.
18. Patient has a known or suspected hypersensitivity to rezatapopt or any of its excipients.
2. Patient has received radiotherapy within 14 days.
3. Patient has a primary CNS tumor.
4. Patient has history of leptomeningeal disease or spinal cord compression.
5. Patient has brain metastases. Exception: Patients with brain metastases are permitted if they are neurologically stable and do not require steroids to treat associated neurological symptoms.

See the full eligibility criteria

Who can join

1. Patient is at least 18 years of age.
10.Patients who are males and have a female partner of childbearing potential must (1) use a condom, both for contraception and to protect any existing pregnancy and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as described in inclusion criterion #9, or (2) agree to be abstinent from heterosexual intercourse as their preferred and usual lifestyle. These requirements should be followed starting with the first dose of study drug through 3 months after the last dose of study drug. Refer to Appendix 2 for contraceptive guidance.
11. Patients must be willing to undergo a tumor biopsy during screening for NGS if an archival tumor specimen is not available and if the procedure is in line with standard of care (i.e., of low risk to patient and the tumor is of sufficient size to be biopsied).
12. Patient has a life expectancy of at least 3 months as assessed by the Investigator.
13. Measurable disease per RECIST v1.1 as assessed by the Investigator, with the last imaging performed within 28 days before C1D1.
2. Patient understands the study procedures and agrees to participate by giving written, signed, and dated informed consent prior to any mandatory study-specific procedures, sampling, or analysis.
3. Patient has an ECOG status of 0 or 1
4. Patient has a histologically or cytologically confirmed locally advanced or metastatic solid malignancy with a TP53 Y220C mutation identified by an analytical validated assay in a certified testing laboratory.
5. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease and have documented radiographic progression during or after their most recent line of anticancer therapy, or in the opinion of the Investigator are ineligible for appropriate standard of care therapy. 5a. Patients with ovarian cancer must be platinum resistant defined as disease progressing within 6 months of platinum-based chemotherapy or platinum-refractory defined as disease progressing during therapy or within 4 weeks after last dose.
6. Patients with CRPC must have ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analog or inhibitor, or orchiectomy (medical or surgical castration).
7. Patient has adequate organ function as defined as: • Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or for patients with Gilbert’s syndrome, direct bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 3.0 x ULN for patients without liver metastasis and ≤ 5.0 x ULN for patients with liver metastasis; albumin > 3g/dl. • Renal: Estimated Glomerular Filtration Rate (eGFR) must be ≥ 40 mL/min. •Hematological: ANC ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL. • Serum potassium, calcium, magnesium, and phosphorus within normal limits or ≤ Grade 1. If values are low on the initial screening assessment, supplements may be given and values repeated to confirm within normal limits or ≤ Grade 1.
8. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to first dose of study drug or be of non-childbearing potential. Non-childbearing potential is defined as: • Postmenopausal, defined as no menses for 12 months without an alternative medical cause. A follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. • Surgically sterile.
9. Patients who are females of childbearing potential must use a highly effective method of contraception for the course of the study or be abstinent from 14 days prior to the first dose of study drug through 3 months after the last dose of study drug .Highly effective methods of contraception include (1) oral, injected, or implanted hormonal methods of contraception that inhibit ovulation, (2) intrauterine device, (3) intrauterine hormone-releasing system, (4) bilateral tubal occlusion/ligation, (5) vasectomized partner with verified absence of sperm in ejaculate post-vasectomy. Barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception. If used, this method must be used in combination with another acceptable method listed above. Refer to Appendix 2 for contraceptive guidance. For patients with breast cancer, the following methods of contraception are not acceptable, and an alternative form of contraception should be used: • Oral, injected, or implanted hormonal methods of contraception • Intrauterine hormone-releasing systems Instead, patients with breast cancer should use one of the following highly effective methods of contraception: • Intrauterine device • Bilateral tubal occlusion/ligation • Vasectomized partner with verified absence of sperm in ejaculate post-vasectomy

What rules you out

1. Patient has received prior chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent within 21 days or 5 half-lives (if half-life is known), whichever is shorter, before receiving their first dose of study drug.
18. Patient has a known or suspected hypersensitivity to rezatapopt or any of its excipients.
2. Patient has received radiotherapy within 14 days.
3. Patient has a primary CNS tumor.
4. Patient has history of leptomeningeal disease or spinal cord compression.
5. Patient has brain metastases. Exception: Patients with brain metastases are permitted if they are neurologically stable and do not require steroids to treat associated neurological symptoms.
6. Patient has had a stroke or transient ischemic attack within 6 months prior to screening.
7. Patient has had one or more of the following cardiac criteria: • Unstable angina within 6 months prior to screening • Myocardial infarction within 6 months prior to screening • New York Heart Association Class II or greater congestive heart failure • QT interval corrected (QTc) using Fridericia’s formula (QTcF) > 470 msec obtained as the mean from 3 consecutive resting ECGs. Exception: A QTcF value corrected for wide QRS > 120 msec (QTcFBBB) should be used in place of QTcF for patients with non-clinically significant wide QRS > 120 msec due to a pacemaker or bundle branch block • Clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block) • Congenital long QT syndrome • Uncontrolled hypertension
8. Patient treated with any of the following medications prior to receiving rezatapopt within the below time windows: • Strong CYP3A4 inducers within 14 days of first dose of rezatapopt • Strong CYP2C9 inhibitors/inducers within 14 days of first dose of rezatapopt
9. Patient has a history of GI disease that may interfere with absorption of study drug (e.g., ulcerative colitis, Crohn’s disease, repeat bowel obstruction, significant nausea or frequent vomiting, severe GERD, severe diarrhea, malabsorption syndrome, or small bowel/gastric resection).
19. Patient whose tumor harbors a known KRAS mutation, defined as a single nucleotide variant (SNV).
10. Patient with dysphagia that could interfere with the ability to swallow tablets.
11. Patient has a history of prior organ transplant.
12. Patient has any medical condition that would, in the Investigator’s judgment, prevent the patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures.
13. Patient has any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer.
14. Patient has a known, active uncontrolled Hepatitis B infection (i.e., viral load above the limit of quantification), Hepatitis C infection (i.e., viral load above the limit of quantification), or human immunodeficiency virus infection (viral load > 400 copies/mL). Patients whose viral load is controlled should be on established antiretroviral therapy for at least 4 weeks prior to receiving their first dose of rezatapopt.
15. Female patients that are breastfeeding or bottle feeding with their breast milk.
16. Patient has any unresolved toxicities from prior anti-cancer therapy greater than Grade 1 at the time of starting rezatapopt treatment with the exception of alopecia and Grade 2 prior chemotherapy induced neuropathy.
17. Patient has had major surgery within 2 weeks prior to the planned start of rezatapopt treatment.

The study team makes the final eligibility decision.

Where it's taking place

Singapore
United Kingdom
Korea, Republic of
United States
Australia

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Singapore; United Kingdom; Korea, Republic of; United States; Australia. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.