BLU-222 for Solid Cancers

No longer recruiting at 24 trial locations

Overseen By Blueprint Medicines

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Blueprint Medicines Corporation

Must not be taking: CDK2 inhibitors

Disqualifiers: Visceral crisis, CNS metastases, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BLU-222, to determine its potential in treating certain solid cancers. Researchers examine its safety, tolerability, and effect on cancer. The trial includes different groups: some receive BLU-222 alone, while others receive it with cancer drugs like Carboplatin, Ribociclib, or Fulvestrant. Individuals with advanced solid tumors, hormone-positive breast cancer, endometrial or gastric cancer, or certain ovarian cancers that have stopped responding to previous treatments might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but you cannot take any prohibited medications or herbal remedies that cannot be stopped at least 2 weeks before starting the study drug.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications, but it mentions that you cannot take certain prohibited medications or herbal remedies within 2 weeks before starting the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that BLU-222, a new treatment under study, is being tested for its safety and effectiveness in treating solid cancers. Early studies have found that BLU-222 specifically targets a protein involved in cell growth, which can be important for treating cancer.

Some patients taking BLU-222 reported vision-related side effects, prompting the FDA to temporarily pause part of the study. This does not mean the treatment is unsafe for everyone; it indicates that researchers are being cautious and working to understand and manage these side effects.

BLU-222 is also being tested in combination with other approved drugs like Carboplatin, Ribociclib, and Fulvestrant. These drugs are already known to be safe, which helps assess the overall safety of these combinations.

Since this trial is in its early stages (Phase 1/2), it mainly focuses on safety. The data collected so far will help determine how well people tolerate the treatment. For those considering joining the trial, it's important to know that safety is a top priority, and any potential risks are being closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BLU-222 for solid cancers because it offers a fresh approach compared to traditional treatments like chemotherapy and targeted therapies. BLU-222 is designed to target specific proteins involved in cancer cell growth, offering a more precise mechanism of action that could potentially lead to fewer side effects. Unlike standard treatments that often require long infusion sessions, BLU-222 is administered orally, which could improve patient convenience and quality of life. Additionally, when combined with other drugs like Carboplatin, Ribociclib, or Fulvestrant, there's hope for enhanced effectiveness against resistant cancer types, making it a promising candidate in the fight against solid tumors.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that BLU-222 is a new treatment targeting a protein called CDK2, which aids cancer growth. Early studies have demonstrated that BLU-222 shows promise both as a standalone treatment and in combination with other cancer drugs. In this trial, participants may receive BLU-222 either as monotherapy or alongside other treatments. Specifically, when combined with carboplatin, BLU-222 proved very effective in tumor models unresponsive to standard chemotherapy. In lab tests, BLU-222 also worked well with ribociclib in certain types of breast cancer. These early results suggest that BLU-222 could be effective against solid tumors, especially when used with other treatments. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, including breast cancer, ovarian cancer, endometrial cancer, and stomach cancer that have worsened despite standard treatments. Participants must not be in a health crisis due to their tumor or have serious heart issues or uncontrolled infections. Women of childbearing potential and men must agree to use effective contraception.

Inclusion Criteria

My endometrial or gastric cancer has worsened after 2 treatments, including a platinum-based therapy.

My cancer has worsened despite standard treatments.

My breast cancer is HR+ HER2- and worsened after CDK4/6 inhibitor treatment.

Exclusion Criteria

I don't have lasting side effects from previous treatments.

I do not have serious heart problems like recent heart attacks or uncontrolled high blood pressure.

I do not have any major surgeries planned within 2 weeks of starting the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BLU-222 as a single agent or in combination with other drugs during dose escalation and expansion phases

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BLU-222

Trial Overview The study is testing BLU-222's safety and effectiveness against various cancers. It's an early-phase trial where patients will receive BLU-222 alone or combined with other drugs like Carboplatin, Ribociclib, or Fulvestrant to see how well they work together.

How Is the Trial Designed?

Group I: BLU-222 Monotherapy Experimental Treatment 2 Interventions

Dose Escalation: Multiple doses for BLU-222 for oral administration Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation

Group II: BLU-222 + Ribociclib + Fulvestrant Experimental Treatment 3 Interventions

Dose Escalation: Multiple doses for BLU-222 for oral administration at doses deemed appropriate based on BLU-222 Monotherapy arm along with Ribociclib and Fulvestrant at the approved doses. Dose Expansion: Oral dose of BLU-222 as determined during dose escalation and approved doses of Ribociclib and Fulvestrant

Group III: BLU-222 + Fulvestrant Experimental Treatment 2 Interventions

Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation + fulvestrant at the approved dose

Group IV: BLU-222 + Carboplatin Experimental Treatment 2 Interventions

Dose Escalation: Multiple doses for BLU-222 for oral administration at doses deemed appropriate based on BLU-222 Monotherapy arm and multiple doses of Carboplatin at the approved dose. Dose Expansion: Oral dose of BLU-222 as determined during Dose Escalation and Carboplatin IV infusion at approved dose

Who Is Running the Clinical Trial?

Blueprint Medicines Corporation

Lead Sponsor

Trials

31

Recruited

6,000+

Published Research Related to This Trial

In a study of 30 patients with HER2-positive breast cancer, a weekly regimen of paclitaxel and carboplatin combined with trastuzumab and pertuzumab achieved a high pathologic complete response (pCR) rate of 77%, comparable to traditional treatments but with fewer severe side effects.

The weekly regimen resulted in no cases of febrile neutropenia or severe peripheral neuropathy, and a split-dose of pertuzumab led to lower rates of grade 2 diarrhea, suggesting it may be a safer alternative to the standard every 3-week TCHP regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study. Lopresti, ML., Bian, JJ., Sakr, BJ., et al.[2022]

The CD44+/CD24- cancer stem cell (CSC) ratio was found to be an independent prognostic factor in breast cancer, with a mean ratio of 8.06% in a study of 1350 patients, indicating its potential to predict patient outcomes.

Higher CSC ratios were significantly associated with lower 5-year breast cancer-specific survival rates and increased distant recurrence, suggesting that this ratio could serve as a predictive marker for chemotherapy effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implications of CD44+/CD24- tumor cell ratio in breast cancer. Liu, C., Luo, Y., Liu, X., et al.[2017]

Apigenin effectively inhibits the survival and migration of prostate cancer stem cells (CSCs) and standard prostate cancer cells (PC3), showing potential as a therapeutic agent against cancer progression.

The mechanism of action involves inducing apoptosis through a caspase-dependent pathway in CSCs and downregulating key signaling pathways (PI3K/Akt/NF-κB), which may help reduce cancer cell proliferation and migration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling. Erdogan, S., Doganlar, O., Doganlar, ZB., et al.[2022]

Cancer stem cells (CSCs) are a unique group of tumor cells that can initiate tumors and self-renew, and their presence in tumors is linked to worse disease progression in patients.

Targeting CSCs with specific therapies could improve cancer treatment outcomes, especially for cancers that do not respond well to standard treatments aimed at the larger tumor cell populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic promise of the cancer stem cell concept. Frank, NY., Schatton, T., Frank, MH.[2023]

This study aims to systematically evaluate the efficacy and safety of weekly cisplatin treatment in breast cancer patients by analyzing various outcomes such as overall survival and quality of life.

The research will critically appraise shared decision-making approaches in randomized controlled trials, ensuring a comprehensive understanding of how cisplatin impacts patient care in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of weekly cisplatin for treatment of patients with breast cancer. Ma, Y., Zhang, NP., An, N., et al.[2022]

The study developed nanoparticles that combine docetaxel (DTX) and sulforaphane (SFN) to effectively target both differentiated breast cancer cells (DBCCs) and breast cancer stem cells (BCSCs), showing enhanced cytotoxicity compared to free drugs.

In vivo results demonstrated that this combination therapy significantly inhibited the self-renewal ability of BCSCs and exhibited the strongest antitumor efficacy, suggesting a promising therapeutic approach for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Targeting of Differentiated Breast Cancer Cells and Breast Cancer Stem Cells by Combination of Docetaxel- and Sulforaphane-Loaded Self-Assembled Poly(D, L-lactide-co-glycolide)/Hyaluronic Acid Block Copolymer-Based Nanoparticles. Huang, J., Tao, C., Yu, Y., et al.[2021]

Breast cancer treatment often fails due to the presence of cancer stem cells (CSCs), specifically breast CSCs (BCSCs), which are resistant to conventional therapies and can lead to disease recurrence.

BCSCs, characterized by a CD44⁺/CD24-/low phenotype and high ALDH activity, are a key focus for future therapies, with ongoing clinical trials exploring drugs that target their specific signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance. Palomeras, S., Ruiz-Martínez, S., Puig, T.[2023]

In a phase II study involving 53 patients with bulky, operable breast cancer, the combination of sequential neoadjuvant docetaxel followed by an anthracycline-based regimen achieved an overall clinical response rate of 81.1%, with 87% of patients able to undergo breast conservation surgery.

While the pathologic complete response rate was lower than hoped, the study demonstrated effective management of myelosuppression through growth factor support, and after 40.4 months of follow-up, only 5 recurrences were noted, indicating promising long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential addition of an anthracycline-based regimen to docetaxel as neoadjuvant chemotherapy in patients with operable breast cancer. Amat, S., Mouret-Reynier, MA., Penault-Llorca, F., et al.[2018]

In a phase II trial involving 76 patients with HER2/neu-negative metastatic breast cancer, the combination of docetaxel and bevacizumab showed a promising objective response rate of 51%, with a median overall survival of 26.3 months.

The treatment was generally well tolerated, with manageable side effects, although common grade 3/4 adverse events included neutropenia (33%) and leukopenia/lymphopenia (25%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01). Hurvitz, SA., Allen, HJ., Moroose, RL., et al.[2020]

In a phase II trial involving 155 women with metastatic breast cancer, a combination of weekly paclitaxel, 5-fluorouracil, and leucovorin showed an overall response rate of 48% and estimated 12-month survival rates of 53% and 65% for different treatment schedules.

The treatment regimen was well tolerated, even among patients with hepatic dysfunction and those over 65 years old, suggesting it could be a suitable first-line therapy for patients who cannot receive anthracycline-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of weekly paclitaxel, 5-fluorouracil, and leucovorin as first-line treatment for metastatic breast cancer. Loesch, DM., Asmar, L., Canfield, VA., et al.[2019]

In a phase II trial involving 54 patients with metastatic breast cancer, the combination of doxorubicin and docetaxel plus G-CSF resulted in a 57% objective response rate, exceeding the target of 50%.

While the treatment showed significant efficacy, 28% of patients experienced a decrease in heart function, and 6% developed congestive heart failure, indicating a need for monitoring cardiac health during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of doxorubicin and docetaxel plus granulocyte colony-stimulating factor in metastatic breast cancer: Eastern Cooperative Oncology Group Study E1196. Sparano, JA., O'Neill, A., Schaefer, PL., et al.[2022]

Only 12% of the 73 phase III trials reviewed for metastatic breast cancer (MBC) showed a significant increase in overall survival (OS), highlighting a major gap in demonstrating clinical benefit from new treatments.

Among the systemic therapies approved for MBC, only four out of twelve were associated with longer survival times, indicating a need for improved trial designs and standards for evaluating treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In the end what matters most? A review of clinical endpoints in advanced breast cancer. Verma, S., McLeod, D., Batist, G., et al.[2023]

In a study of 91 taxane-refractory metastatic breast cancer patients, eribulin demonstrated clinical benefit in 45.2% of patients, with a median overall survival of 11.6 months.

Eribulin was generally well tolerated, although common side effects included fatigue (58%) and neutropenia (30%), leading to dose reductions in 19 patients and treatment suspension in 9.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of eribulin in taxane-refractory patients in the 'real world'. Lorusso, V., Cinieri, S., Latorre, A., et al.[2017]

In a study of 31 heavily pretreated metastatic breast cancer patients, eribulin demonstrated a median progression-free survival of 2.0 months and an overall survival of 5.5 months, indicating its potential efficacy in this patient population.

The treatment was particularly effective for patients with bone metastases, showing a response rate of 13.6%, which was higher than responses observed for other types of metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin efficacy based on type of metastatic site: a real-life study in heavily pretreated metastatic breast cancer. Prestifilippo, A., Grippaldi, D., Blanco, G., et al.[2017]

In a study of 881 patients aged 65 and older with metastatic renal cell carcinoma (mRCC), 60% experienced adverse events (AEs) related to targeted therapies, leading to significantly higher healthcare costs.

Patients with AEs incurred an average cost of $13,944 over 30 days, compared to just $1,878 for those without AEs, highlighting the financial impact of managing these toxicities and suggesting that better management could reduce overall healthcare expenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic burden of selected adverse events in patients aged ≥65 years with metastatic renal cell carcinoma. Hagiwara, M., Hackshaw, MD., Oster, G.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05252416

(VELA) Study of BLU-222 in Advanced Solid Tumors A Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of BLU-222 as a Single Agent and in Combination Therapy for Patients With Advanced ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11967718/

Profiling the Activity of the Potent and Highly Selective ... BLU-222 demonstrated robust activity in combination with carboplatin or paclitaxel in CCNE1-aberrant models, rendering chemotherapy-resistant tumors strongly ...

3. blueprintmedicines.com blueprintmedicines.com/wp-content/uploads/2023/06/Blueprint-Medicines-ASCO-2023-BLU-222-VELA-Monotherapy-Dose-Escalation-Poster.pdf

BLU-222, an oral, potent and selective CDK2 inhibitor, in ... BLU-222 monotherapy. (ongoing). Advanced solid tumors (N≈50–70). Progression on SOC treatment. BLU-222 with carboplatin. (planned). Platinum ...

4. clinicaltrial.be clinicaltrial.be/en/details/32327?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

(VELA) Study of BLU-222 in Advanced Solid Tumors This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), ...

5. aacrjournals.org aacrjournals.org/cancerres/article/83/5_Supplement/OT3-23-01/717955/Abstract-OT3-23-01-VELA-A-first-in-human-phase-1-2

VELA: A first-in-human phase 1/2 study of BLU-222, a potent ... BLU-222 is an oral, investigational, potent, and selective CDK2 inhibitor. In preclinical studies, BLU-222 treatment in combination with ribociclib led to ...

6. onclive.com onclive.com/view/fda-places-partial-clinical-hold-on-vela-trial-with-blu-222-in-advanced-solid-tumors

FDA Places Partial Clinical Hold on VELA Trial With BLU ... The FDA has placed a partial clinical hold on the phase 1/2 VELA trial due to visual adverse effects observed in select patients who received the ...

7. withpower.com withpower.com/trial/phase-2-malignant-neoplasm-of-stomach-1-2022-306ec

BLU-222 for Solid Cancers · Info for Participants What safety data is available for BLU-222 in solid cancers? The provided research does not contain any safety data for BLU-222 or its variants. The studies ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05252416?tab=history&a=11

(VELA) Study of BLU-222 in Advanced Solid Tumors Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...