A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of INX-315 in Patients With Advanced Cancer

Plain English Summary

Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer is a Phase 2 clinical trial sponsored by Incyclix Bio studying Breast Cancer, Breast Cancer Metastatic, Hormone Receptor Positive Tumor, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Ovarian Cancer, CCNE1 Amplification, Solid Tumor, Advanced Cancer, Metastatic Cancer. This trial tests a new drug called INX-315, which targets a specific protein (CDK2) involved in cancer growth. It is for patients with advanced or metastatic breast cancer, ovarian cancer, or other solid tumors that have not responded to previous treatments. Participation involves taking the study drug, either alone or with other cancer medications, and attending regular clinic visits for monitoring. Alternative treatments include standard chemotherapy, hormone therapy, or other targeted therapies depending on the cancer type and previous treatments. The trial aims to enroll 150 participants.

Official Summary

Incyclix Bio (Incyclix) is developing INX-315 as an oral, small molecule inhibitor of cyclin dependent kinase 2 (CDK2) for the treatment of human cancers. This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumor activity of INX-315 in patients with recurrent advanced/metastatic cancer, including hormone receptor positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer who progressed on a prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) regimen, and CCNE1-amplified solid tumors who progressed on standard of care treatment. The study will be conducted in 3 parts: Part A (INX-315 monotherapy dose escalation and combination therapy with fulvestrant), Part B (ovarian cancer INX-315 monotherapy dose expansion), and Part C (INX-315 combination therapy with abemaciclib \[a CDK4/6i\] and fulvestrant \[a SERD\] in advanced/metastatic breast cancer; dose escalation and expansion).

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with advanced or metastatic breast cancer that has worsened after treatment with a CDK4/6 inhibitor. Patients with advanced ovarian cancer or other solid tumors with a specific genetic change (CCNE-1 amplification) that have progressed on standard treatments. Patients must have at least one measurable tumor, be in good general health (ECOG 0-1), and have adequate organ function. Patients who have previously received a CDK2 inhibitor or have certain serious medical conditions, active infections, or uncontrolled cardiovascular disease cannot participate. This trial is studying Breast Cancer, Breast Cancer Metastatic, Hormone Receptor Positive Tumor, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Ovarian Cancer, CCNE1 Amplification, Solid Tumor, Advanced Cancer, Metastatic Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the drug is and if it can shrink tumors, which will help determine if it's effective and worth pursuing for further development. The specific primary outcome measures are: Part A and B: Evaluate the incidents of treatment emergent adverse events and laboratory abnormalities in INX-315 monotherapy and in combination with fulvestrant (Up to 12 months); Part A: Evaluate the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 (28 days); Part A: Recommend at least two doses of INX-315 to be evaluated in the expansion phase (Up to 12 months); Part B: Overall response rate (ORR) (Up to 36 months); Part B: Selection of Recommended Phase 2 Dose (RP2D) (Up to 36 months). 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 is important because it explores a new approach to treating cancers that have become resistant to existing therapies, potentially filling a gap for patients with limited options. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Cancer, Breast Cancer Metastatic, Hormone Receptor Positive Tumor, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Ovarian Cancer, CCNE1 Amplification, Solid Tumor, Advanced Cancer, Metastatic Cancer, where improved treatment options are needed.

Investor Insight

This trial represents an early-stage investment in a novel targeted therapy for difficult-to-treat cancers, with potential for significant market impact if successful. 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 specific goals of this trial for your type of cancer and what side effects you might expect. Be prepared for regular clinic visits for drug administration, blood tests, and physical exams to monitor your health and response to treatment. Understand that you may receive the study drug alone or in combination with other approved cancer treatments. This trial is currently recruiting participants. The trial is being conducted at 18 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: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 150 participants

Interventions

• DRUG: INX-315 — Oral administration
• DRUG: Fulvestrant — Fulvestrant will be combined with INX-315
• DRUG: Abemaciclib — Abemaciclib will be combined with INX-315

Primary Outcomes

• Part A and B: Evaluate the incidents of treatment emergent adverse events and laboratory abnormalities in INX-315 monotherapy and in combination with fulvestrant (Up to 12 months)
• Part A: Evaluate the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 (28 days)
• Part A: Recommend at least two doses of INX-315 to be evaluated in the expansion phase (Up to 12 months)
• Part B: Overall response rate (ORR) (Up to 36 months)
• Part B: Selection of Recommended Phase 2 Dose (RP2D) (Up to 36 months)

Secondary Outcomes

• Characterize the maximum plasma concentration (Cmax) (Cycle 1 Day 1 and Day 15)
• Characterize the time to maximum plasma concentration (Tmax) (Cycle 1 Day 1 and Day 15)
• Characterize the Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-24h) (Cycle 1 Day 1 and Day 15)
• Characterize the terminal half-life (t1/2) (Cycle 1 Day 1 and Day 15)
• Characterize the oral clearance (CL/F) (Cycle 1 Day 1 and Day 15)

Full Eligibility Criteria

Inclusion Criteria:

1. Advanced unresectable or metastatic HR+/HER2- BC that has progressed following treatment with a CDK4/6 inhibitor in the adjuvant or advanced/metastatic setting.
2. Advanced/ metastatic platinum-resistant or platinum-refractory high grade serous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, with known amplification of CCNE-1 that progressed after standard systemic therapy
3. Advanced or metastatic solid tumor with known amplification of CCNE-1 that has progressed after standard therapy, been intolerant to or is ineligible for standard therapy
4. At least one measurable lesion as defined by RECIST v1.1 that has not previously been irradiated
5. ECOG performance status score of 0 or 1.
6. Adequate organ function as demonstrated by the following laboratory values:

   1. Hemoglobin ≥ 9.0 g/dL
   2. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L
   3. Platelet count ≥ 100 × 10\^9/L
   4. Estimated glomerular filtration rate (eGFR) of ≥60 mL/min
   5. Part A and B: Total bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN; ≤ 5 × ULN in the presence of liver metastases Part C: Patients with Gilbert's syndrome with a total bilirubin ≤ 2.0 × ULN and direct bilirubin within normal limits
7. Negative pregnancy test

Exclusion Criteria:

1. Have received previous therapy with a CDK2/4/6 inhibitor or CDK2 inhibitor.
2. Have central nervous system (CNS) metastases or spinal cord compression that is associated with progressive neurological symptoms or requires corticosteroids (within 4 weeks of enrollment) to control the CNS disease.
3. Have known intracranial hemorrhage and/or bleeding diatheses.
4. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
5. Have clinically active ongoing interstitial lung disease (ILD) of any etiology, including drug-induced ILD, and radiation pneumonitis within 28 days prior to initiation of study treatment.
6. Resting QTcF \> 470 msec, a history of prolonged QT syndrome or Torsades de pointes, or a familial history of prolonged QT syndrome.
7. Uncontrolled, cardiovascular disease (including hypertension) with or without medication
8. History of other malignancies, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated a) in situ carcinoma of the uterine cervix, b) prostate cancer, or c) superficial bladder cancer; or (3) other curatively treated solid tumor with no evidence of disease for ≥ 3 years.
9. Known HIV infection, including AIDS-related illness, or have active, uncontrolled infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B virus, hepatitis C virus, or COVID-19 infection (symptoms and a positive test result).
10. Requires treatment with a prohibited medication or herbal remedy that cannot be discontinued at least 2 weeks before the start of study drug administration.
11. Have planned or anticipation of the need for major surgical procedure within 28 days of the first dose of study drug (procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures).
12. Unwilling or unable to comply with scheduled visits, study drug administration plan, laboratory tests, or other study procedures and study restrictions.
13. Radical radiotherapy within 28 days prior to study entry or palliative radiotherapy within 2 weeks prior to study entry.
14. Systemic anti-cancer therapy within 21 days or at least 5 half-lives, whichever is less, prior to the first dose of the study drug
15. Prior irradiation to \> 25% of the bone marrow
16. Previous high-dose chemotherapy requiring prior stem cell transplant
17. Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry.
18. Known or suspected hypersensitivity to active ingredient/excipients in INX-315 or fulvestrant or abemaciclib.
19. Known difficulty in swallowing or tolerating oral medications, or conditions which would impair absorption of oral medications such as active inflammatory gastrointestinal disease, uncontrolled nausea or vomiting (i.e., CTCAE ≥ Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility disorder/active inflammation, malabsorption syndrome, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
20. Has a serious and/or uncontrolled pre-existing medical condition(s) that, in the judgment of the Investigator or the Sponsor, would preclude participation in this study (for example but not limited to, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)

Trial Locations

• Florida Cancer Specialists, Orlando, Florida, United States
• Emory Winship Cancer Institute, Atlanta, Georgia, United States
• Georgia Cancer Center at Augusta University, Augusta, Georgia, United States
• Fort Wayne Medical Oncology and Hematology, Fort Wayne, Indiana, United States
• Dana-Farber Cancer Institute, Boston, Massachusetts, United States
• Karmanos Cancer Institute, Detroit, Michigan, United States
• Roswell Park Cancer Institute, Buffalo, New York, United States
• Levine Cancer Institute (LCI)- Atrium Health, Charlotte, North Carolina, United States
• Duke Cancer Center/ DUMC, Durham, North Carolina, United States
• Gabrail Cancer Research Center, Canton, Ohio, United States
• ...and 8 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• Hormone Receptor Positive Breast Cancer
• HER2- Negative Breast Cancer
• Ovarian Cancer
• Solid Tumors
• Metastatic Cancer
• Advanced Cancer
• CCNE1 Amplification
• Cancer Treatment Resistance

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