A Phase II, Open-Label, Multicenter Clinical Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of TT-00420 (Tinengotinib) Tablets Combined With Fulvestrant Injection in Patients With Hormone Receptor-Positive (HR+) and Human Epidermal Growth Factor Receptor 2 (HER-2) Negative or Low-Expressing Recurrent or Metastatic Breast Cancer Who Have Failed Prior Treatment

Plain English Summary

Efficacy and Safety of Tinengotinib Tablets Combined With Fulvestrant Injection in Patients With HR Positive and HER-2 Negative Recurrent or Metastatic Breast Cancer Who Have Failed Prior Treatment is a Phase 2 clinical trial sponsored by TransThera Sciences (Nanjing), Inc. studying Breast Cancer. This trial tests a new combination therapy (tinengotinib and fulvestrant) for advanced breast cancer. It is for patients with hormone-receptor-positive (HR+) and HER2-negative or low-expressing breast cancer that has spread and did not respond to previous treatments. Participants will take the study drugs, and their health will be closely monitored. Alternative treatments may include chemotherapy or other targeted therapies, depending on prior treatments and disease progression. The trial aims to enroll 94 participants.

Official Summary

The goal of this clinical trial is to learn if tinengotinib combined with fulvestrant works to treat patients with HR-Positive and HER-2-Negative or low-expressing advanced breast cancer. It will also learn about the safety of combination therapy. The main questions it aims to answer are: 1. Does tinengotinib combined with fulvestrant reduce the tumor burden in participants? 2. What medical problems do participants have when taking the combination therapy? Participants will: Take tinengotinib and fulvestrant to find the optimal dose of tinengotinib for the combination therapy in Part A. In Part B, will take tinengotinib at the optimal dose with fulvestrant or tinengotinib alone to see if the combination therapy works better than tinengotinib monotherapy.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with HR+/HER2- advanced breast cancer that has spread and has not responded to up to 2 prior endocrine therapies and at least one CDK4/6 inhibitor. Patients must be postmenopausal or have had their ovaries removed, or be on ovarian suppression therapy. Patients must have measurable disease and good organ and bone marrow function. Patients with brain metastases, uncontrolled high blood pressure, or recent severe cardiac/cerebrovascular events cannot join. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will determine if the combination therapy shrinks tumors and how safe it is, meaning it will show if the new treatment can effectively control the cancer and what side eff The specific primary outcome measures are: Part A: safety evaluation parameters (From signing of the informed consent until 28 days after the last dose or the end of the study (whichever occurs first), an average of 1 year.); Part B: Objective Response Rate (ORR) (RECIST v1.1) (From first study drug administration to the end of treatment, an average of 1 year.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a significant unmet need for patients with advanced HR+/HER2- breast cancer who have progressed after standard therapies, offering a potential new treatment option. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a large market of patients with advanced breast cancer, aiming to fill a gap in treatment options after progression on CDK4/6 inhibitors, suggesting a potentially high probability o Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of tinengotinib and fulvestrant, and how this combination compares to other available treatments. Participation involves taking study medications, attending regular clinic visits for monitoring, and undergoing tests to assess tumor response and overall health. Be prepared for potential side effects and discuss any concerns with your healthcare team promptly. This trial is currently recruiting participants. The trial is being conducted at 13 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 94 participants

Interventions

• DRUG: Tinengotinib at the optimal dose combined with Fulvestrant — Participants will receive tinengotinib at the optimal dose once daily with fulvestrant in 28-day cycles per protocol defined schedule.
• DRUG: Tinengotinib — Participants will receive tinengotinib once daily in 28-day cycles per protocol defined schedule.
• DRUG: tinengotinib combined with fulvestrant — Participants will take tinengotinib at the starting dose of 10 mg once daily with fulvestrant to determine the optimal dose of tinengotinib in combination with fulvestrant. If not tolerated, the dose of tinengotinib will be reduced to 8 mg or 6 mg once daily.

Primary Outcomes

• Part A: safety evaluation parameters (From signing of the informed consent until 28 days after the last dose or the end of the study (whichever occurs first), an average of 1 year.)
• Part B: Objective Response Rate (ORR) (RECIST v1.1) (From first study drug administration to the end of treatment, an average of 1 year.)

Full Eligibility Criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed breast cancer with evidence of local recurrence or distant metastasis and no indication for surgery or radiotherapy;
2. Breast cancer confirmed as HR+/HER2- negative or low expression by local laboratory testing based on the most recent tumor tissue sample (from either the primary or metastatic site, excluding bone lesions). HR-positive, HER2-negative or low expression as defined in this study refer to the Chinese Society of Clinical Oncology \[CSCO\] 2024 criteria;
3. Participants must meet at least one of the following criteria: a) prior bilateral oophorectomy, or age ≥60 years; b) age \<60 years, with natural amenorrhea (in the absence of medication or pathological conditions) for ≥12 months, and estradiol and FSH levels within the postmenopausal range; c) age \<60 years, currently undergoing ovarian suppression therapy (e.g., LHRH agonist) and requiring continued treatment during the study, with estradiol and FSH levels maintained within the postmenopausal range;
4. Participants who have previously failed 1-2 lines of endocrine therapy (including AI, SERD, and SERM) for recurrent or metastatic disease are eligible. Subjects with initial diagnosis showing weak ER positivity by IHC (tumor cells with nuclear staining accounting for 1%-10%) are not eligible for enrollment;
5. Participants must have experienced disease progression after prior treatment with at least one CDK4/6 inhibitor (CDK4/6i), including in the neoadjuvant, adjuvant, or systemic treatment settings;
6. Participants who have previously failed 0-2 lines of systemic chemotherapy (cytotoxic drugs) for recurrent or metastatic disease. Antibody-drug conjugates (ADCs) are not counted as systemic chemotherapy;
7. ECOG ≤ 1;
8. Participants must meet at least one of the following criteria (per RECIST v1.1): a) At least one measurable lesion as defined by RECIST v1.1 at baseline; if the only target lesion is a non-nodal lesion, its longest diameter must be ≥15 mm; b) When bone lesions are the only measurable lesions, lytic or mixed bone lesions may be selected as target lesions; subjects with only blastic bone lesions are not eligible for enrollment.
9. Adequate organ and bone marrow function;
10. Premenopausal participants receiving ovarian suppression therapy must agree to use adequate contraception to avoid pregnancy during the study and for at least 3 months after the end of treatment;
11. Able to sign informed consent and comply with the protocol.

Exclusion Criteria:

1. Participants who are pregnant or breastfeeding;
2. Conditions judged by the investigator as making the participant unsuitable for study drug treatment, including but not limited to: a history of severe allergy to the components or excipients of the study drug, prior treatment history with the study drug, or presence of complications that may be life-threatening in the short term (such as pleural, pericardial, or abdominopelvic effusions that cannot be controlled by drainage or other methods);
3. Uncontrolled hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg), allowing for the lowest value from up to two repeat measurements;
4. Participants with brain or central nervous system (CNS) metastases that have progressed as confirmed by imaging or clinically within 28 days before the start of treatment (e.g., evidence of new or enlarging brain metastases on imaging, new neurological symptoms attributable to brain/CNS metastases);
5. Participants with concurrent other malignancies or hematologic malignancies that are progressing or require active treatment (excluding basal cell carcinoma of the skin, other non-invasive or indolent malignancies, or cured tumors); Hormone replacement therapy is permitted (e.g., thyroxine replacement therapy post-thyroidectomy);
6. Participants who have received systemic treatment with corticosteroids (\>10 mg/day of prednisone or equivalent dose of other corticosteroids) or other immunosuppressive medications within 14 days prior to the initiation of the study drug;
7. Participants who have received other systemic anti-tumor therapies or treatment with investigational drugs prior to the initiation of the study drug, with a washout period of approximately 5 half-lives or 14 days, whichever is shorter;
8. Participants who have received extensive radiotherapy or major surgery within 4 weeks prior to the initiation of the study drug, or local palliative radiotherapy within 2 weeks. (If the investigator judges that this does not pose an additional safety risk, initiation of the study drug during the washout period may be permitted with sponsor agreement.)
9. Participants who have not yet recovered from adverse events resulting from prior anti-tumor therapy (excluding adverse events ≤ Grade 1 per CTCAE, or ≤ Grade 2 adverse events that the investigator judges do not pose a safety risk).
10. History of severe cardiac or cerebrovascular disease;
11. Participant

Trial Locations

• Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
• Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
• Hunan Cancer Hospital, Changsha, Hunan, China
• Jiangsu Province Hospital, Nanjing, Jiangsu, China
• Shandong Cancer Hospital, Jinan, Shandong, China
• Linyi Cancer Hospital, Linyi, Shandong, China
• Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
• Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
• Beijing Cancer Hospital, Beijing, China
• The First Medical Center, Chinese PLA General Hospital, Beijing, China
• ...and 3 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Negative Breast Cancer
• Metastatic Breast Cancer
• Recurrent Breast Cancer
• Endocrine Therapy Resistance
• CDK4/6 Inhibitor Resistance
• Advanced Breast Cancer
• Oncology
• Solid Tumors

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