A multi-center, open-label Phase 1/2 study to evaluate the safety, efficacy, PK and PD of ONA-255 in study participants with advanced cancer

Study Identifier:
ONA-255-101
CT.gov Identifier:
N/A
EudraCT Identifier:
202552000000
EU Trial (CTIS) Number:
2025-522233-62-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study Summary

Phase 1a: Determine the minimum biological active dose (MBAD), and the maximum tolerated dose (MTD) of ONA 255 single agent. Phase 1b: Determine the optimal dose and recommended Phase 2 dose (RP2D) of ONA 255 single agent in HR+/HER2- aBC If applicable: Determine the optimal dose and RP2D of ONA 255 in metastatic GC/GEJ cancer Phase 2a: Assess the preliminary Overall Response Rate of ONA-255 single agent at the RP2D level

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Breast Cancers
Gastric
Solid Tumor
Digestive & Intestinal
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
N/A
Age
18+ years
Study Drug
Drug: Patients will receive ONA‑255
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • 1 1. Female/male with advanced breast cancer or metastatic gastric /gastroesophageal junction cancer ≥ 18 years of age on date of informed consent signature
  • 10 8. For male study participants: if fertile and sexually active, and the partner is of childbearing potential (see definition in inclusion #7), agrees to use methods of highly effective contraception (see definition in inclusion criterion #7) during the study and for 3 months and 20 days after the last treatment with ONA-255
  • 11 9. Has a life-expectancy of ≥ 6 months
  • 12 10. Has given written informed consent before start of any study-specific activity
  • 13 11. Is willing and able to comply with the requirements of the protocol
  • 2 2. Histopathologically confirmed advanced HR+/HER2- breast cancer, based on either a new biopsy obtained from a metastatic lesion during screening or an archival formalin fixed paraffin-embedded (FFPE) metastatic tissue sample collected within 12 months prior to the date of screening. HR+ is defined as estrogen receptor (ER) and/or progesterone receptor (PR) expression in more than 1% of tumour cells. HER2- is defined as an immunohistochemistry (IHC) score of 0–1+ or 2+ with a negative FISH, CISH, or SISH test. OR Histopathological confirmed metastatic gastric / gastroesophageal adenocarcinoma. Either new biopsy from metastatic lesion during screening or archival biopsy sample from a metastatic lesion (paraffin embedded) which was collected within 12 months from the date of screening needs to be available
  • 3 3. Phase 1a: Participants with advanced HR+/HER2- breast cancer or metastatic gastric/gastroesophageal junction cancer who have no effective or tolerable standard therapy options, or for whom standard-of-care therapy is unavailable or inappropriate.
  • 4 3. Phase 1b: aBC cohorts: Participants with advanced HR+/HER2- breast cancer who has progressive or primary resistant disease following at least 1 line of standard endocrine therapy—including a CDK4/6 inhibitor—and at least 1 line of chemotherapy or antibody-drug conjugate. This includes chemotherapy administered within 1 year prior to study enrollment in the early disease setting. OR If applicable (cohort is opened for enrolment) – metastatic GC/GEJ cancer cohort(s): Participants with metastatic gastric or gastroesophageal junction cancer who have progressed or shown primary resistance after at least 2 lines of standard therapy. For HER2-positive patients, treatment must have included trastuzumab-based therapy.
  • 5 3. Phase 2a: aBC cohort: Participants with advanced HR+/HER2- breast cancer who has progressive or primary resistant disease following at least 1 line of standard endocrine therapy—including a CDK4/6 inhibitor—and at least 1 line of chemotherapy or antibody-drug conjugate, but not more than 3 lines of chemotherapy or antibody-drug conjugate. This includes chemotherapy administered within 1 year prior to study enrollment in the early disease setting. OR If applicable (cohort is opened for enrolment) – metastatic GC/GEJ cancer cohort: • Participants with metastatic gastric or gastroesophageal junction cancer who have progressed or shown primary resistance after at least 2 lines of standard therapy. For HER2-positive participants, treatment must have included trastuzumab-based therapy. • Participants with HER2-negative metastatic gastric or gastroesophageal junction cancer who have progressed or shown primary resistance after at least 1 line of standard therapy and have contraindications to antiangiogenic treatment.
  • 6 4. ECOG performance status of 0 or 1
  • 7 5. Adequate laboratory values for bone marrow (without transfusion support less than 1 week ago) and organ function: •Absolute neutrophil count ≥ 1.5 x 109/L •Platelets ≥ 75 × 109/L •Haemoglobin ≥ 9 g/dL without RBC transfusion within 7 days of screening •Potassium, sodium, and calcium (corrected for serum albumin), within normal limits •Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥60 ml/min for study participants with serum creatinine ≥ 1.5 × ULN (calculated by the Cockcroft-Gault Method) •In absence of liver metastasis, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN. If the study participant has liver metastases, ALT and AST should be ≤ 5 × ULN. •Total serum bilirubin ≤ 1.5 x ULN; (total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in study participants with Gilbert‘s Syndrome).
  • 8 6. At least 1 measurable lesion per RECIST 1.1
  • 9 7. If female of childbearing potential, agrees to use highly effective form of contraception during the study and for 6 months and 20 days after the last treatment with ONA-255 or is of postmenopausal status. • Highly effective methods of contraception as defined by: i. Bilateral tubal ligation ii. Hormonal contraception iii. Intrauterine device iv. Vasectomised sexual partner (provided that partner is the sole sexual partner of the WOCBP study participant and that the vasectomised partner has received medical assessment of the surgical success) v. Sexual abstinence, ie, refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the study participant) •Postmenopausal status as defined by: vi. Prior bilateral oophorectomy vii. Age ≥ 60 years viii. Age < 60 years and amenorrhoea for ≥ 12 months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range
Exclusion criteria
  • 1 1. Brain metastases that are untreated, symptomatic, or require medication to control symptoms, or if treated, are not stable for at least 2 weeks
  • 10 10. Known human immunodeficiency virus (HIV) infection or active hepatitis (HBV or HCV)
  • 11 11. Severe acute or chronic medical condition (eg, not well controlled diabetes, keratitis, pneumonitis), substance abuse, or psychiatric condition, that in the judgment of the investigator, would put the study participant at a high risk of unwarranted side effects or prevent the participant from being compliant with study procedures or may confound the study interpretation
  • 12 12. Patients with large amount of pleural effusion or ascites requiring more than weekly drainage
  • 13 13. Known auto-immune hepatitis Spanish:Hepatitis autoinmune conocida
  • 14 14. Infection requiring intravenous antibiotic treatment within 1 week prior to enrolment
  • 15 15. Requiring immunosuppressive therapy or systemic daily chronic corticosteroids above methylprednisolone equivalent of ≥ 10 mg/day
  • 16 16. Laboratory abnormality that may increase the risk associated with investigational product administration or may interfere with the interpretation of study results
  • 17 17. Concurrent other malignancy or malignancy within 3 years of enrolment, with the exception of adequately treated, basal or squamous cell carcinoma, non melanomatous skin cancer or curatively resected cervical cancer with no evidence of disease within the last 1 year
  • 18 18. Known or suspected allergies or hypersensitivities to any of the excipients of the study drug ONA-255 (refer to the IB)
  • 19 19. Has previously received a FGFR4 inhibitor or an MMAE ADC in a clinical study
  • 2 2. Visceral crisis with signs and symptoms of impeding or manifested severe organ dysfunction
  • 20 20. Currently pregnant, breastfeeding, or lactating
  • 21 21. Psychological, social, familial, or geographic factors that would prevent the study participant to attend study visits
  • 22 22. Study participants under guardianship or family empowerment measures.
  • 3 3. Major surgery, chemotherapy, radiotherapy, investigational agent, or other anticancer therapy (within 3 weeks before enrolment for myelotoxic therapies and 14 days for non myelotoxic therapies)
  • 4 4. Prior radiation therapy to ≥ 25% of the bone marrow
  • 5 5. Prior therapy with an antibody-drug conjugate within 5 half-lives or 4 weeks (whatever is shorter) of enrolment
  • 6 6. Have received a strong CYP3A inducer within 21 days of the first study drug administration or a strong CYP3A inhibitor within 14 days of the first dose of study drug. S
  • 7 7. QTc interval is > 470 msec (average of screening triplicate ECG) or a family or personal history of long QT syndrome
  • 8 8. Known abnormalities in coagulation, that in the judgment of the investigator, increase the safety risk
  • 9 9. Unresolved toxicity from previous anti-cancer treatment of ≥ Grade 2 (NCT CTCAE grading version 5.0). Study participants with alopecia of Grade 2 are not excluded. Persistent ≥ Grade 1 neuropathy (NCT CTCAE grading version 5.0)

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Juan José Soto
Status
Recruiting
Condition(s) Treated at Site
Breast Cancers
Gastric
Solid Tumor
Digestive & Intestinal