CYT-0851 for Cancer

No longer recruiting at 17 trial locations

Overseen By Pamela Munster, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Cyteir Therapeutics, Inc.

Must not be taking: Antibiotics, Antifungals, Antivirals, Corticosteroids

Disqualifiers: HIV, Hepatitis, Stroke, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment called CYT-0851 for certain types of cancer, including difficult-to-treat B-cell blood cancers and advanced solid tumors. Researchers seek to determine the best dose of CYT-0851 when used alone and in combination with other chemotherapy drugs. Potential participants include those who have tried other treatments without success, such as individuals with relapsed or hard-to-treat B-cell malignancies or advanced solid tumors like breast or ovarian cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot be on certain medications like those that prolong the QTc interval or narrow therapeutic index drugs sensitive to CYP3A, P-gp, or BCRP without approval. There is also a 14-day washout period for some therapies.

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

A previous study found that CYT-0851 was generally well-tolerated when used alone, with no unexpected side effects at effective doses. When combined with capecitabine, the safety was also deemed acceptable, as patients handled the combination well and the treatment showed positive results.

For the combination of CYT-0851 with rituximab and bendamustine, existing safety information on rituximab and bendamustine shows an acceptable safety profile in similar situations.

Lastly, CYT-0851 mixed with gemcitabine also appeared well-tolerated, with no surprising side effects noted in early findings. Overall, early data suggests that CYT-0851, whether used alone or in combinations, has a manageable safety profile for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CYT-0851 for cancer because it offers unique combinations and mechanisms compared to existing treatments. Unlike the standard chemotherapy options, CYT-0851 can be administered orally, making it more convenient for patients. Additionally, CYT-0851 is being tested in combination with other drugs like capecitabine, rituximab, bendamustine, and gemcitabine, potentially enhancing its effectiveness. These combinations could provide a more targeted approach to cancer treatment, potentially improving outcomes and reducing side effects.

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

Research has shown that CYT-0851 yields promising results in cancer treatment. In this trial, participants may receive CYT-0851 alone, which controlled the disease for several months. Another treatment arm combines CYT-0851 with capecitabine, which controlled the disease in 71.4% of patients with advanced solid tumors in previous studies. Additionally, some participants will receive CYT-0851 with rituximab and bendamustine, treatments that have demonstrated high success rates in treating B-cell cancers. The combination with gemcitabine, another treatment arm in this trial, has also shown early positive results. Overall, these findings suggest that CYT-0851, whether used alone or with other drugs, could effectively manage various cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

Markus Renschler, MD

Principal Investigator

Cyteir Therapeutics

Are You a Good Fit for This Trial?

Adults with certain B-cell malignancies or advanced solid tumors who understand the study and consent to participate. They must have a specific type of tumor, measurable disease, be in good physical condition (ECOG 0-1), and agree to use contraception if necessary. Excluded are those unable to swallow pills, recent heart attack or stroke victims, uncontrolled hypertension sufferers, individuals with active CNS metastases or significant health issues that could affect safety.

Inclusion Criteria

My cancer is a type of B cell malignancy confirmed by testing.

I can and agree to have a biopsy, or I can provide a recent sample if needed.

Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure

Exclusion Criteria

I have not had a heart attack or stroke in the last 6 months.

I haven't had cancer treatment in the last 14 days.

I had hepatitis C but completed treatment and now have an undetectable viral load.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Dose Escalation

CYT-0851 administered orally in rising doses QD or BID for 28 day cycles

28 days per cycle

Treatment - Combination Therapy

CYT-0851 administered with various combinations: capecitabine, rituximab and bendamustine, or gemcitabine

21-28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• Capecitabine
• CYT-0851
• Gemcitabine
• Rituximab

Trial Overview The trial is testing CYT-0851 alone and combined with other chemotherapy drugs like rituximab and bendamustine or gemcitabine in patients with relapsed/refractory B-cell malignancies and advanced solid tumors. The goal is to determine safe dosages for Phase 2 trials.

How Is the Trial Designed?

Group I: CYT-0851 dose expansion Experimental Treatment 1 Intervention

Part B: CYT-0851 administered orally at the selected Phase 2 dose for 28 day cycles

Group II: CYT-0851 dose escalation Experimental Treatment 1 Intervention

Part A: CYT-0851 administered orally in rising doses QD or BID for 28 day cycles

Group III: CYT-0851 and rituximab and bendamustine Experimental Treatment 2 Interventions

Part C: Daily oral doses of CYT-0851 for 28 days in combination with rituximab on Day 1 and bendamustine on Days 1 and 2 of each 28 day cycle

Group IV: CYT-0851 and gemcitabine Experimental Treatment 2 Interventions

Part D: Daily oral doses of CYT-0851 for 28 days in combination with gemcitabine on Day 1, 8 and 15 of each 28 day cycle

Group V: CYT-0851 and capecitabine Experimental Treatment 2 Interventions

Part E: Daily oral doses of CYT-0851 for 21 days in combination with capecitabine on Days to 14 of each 21 day cycle

Who Is Running the Clinical Trial?

Cyteir Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

170+

Published Research Related to This Trial

In a study of 36 patients with advanced non-small cell lung cancer (NSCLC), the combination of irinotecan and cisplatin showed a partial response rate of 22.9% and a stable disease rate of 60%, indicating its efficacy in this patient population.

The treatment was associated with manageable adverse events, with grade III/IV side effects occurring in a minority of patients, including neutropenia (16.7%) and alopecia (13.9%), suggesting that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer]. Zhang, XR., Zhu, YZ., Xiu, QY., et al.[2018]

In a phase II study involving 70 patients with advanced non-small cell lung cancer (NSCLC), the combination of irinotecan (CPT-11) and cisplatin resulted in a promising objective response rate of 52%, with one complete response and 32 partial responses.

The treatment demonstrated a median survival time of 44 weeks and a 1-year survival rate of 33%, while the major toxicities included leucopenia and diarrhea, affecting a significant portion of patients but deemed acceptable in the context of the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of combination of CPT-11 and cisplatin for advanced non-small-cell lung cancer. CPT-11 Lung Cancer Study Group. Masuda, N., Fukuoka, M., Fujita, A., et al.[2019]

In a phase II study involving 45 patients with advanced colorectal cancer, the combination of oral S-1 and weekly irinotecan showed an overall response rate of 48.9%, indicating significant efficacy as a first-line treatment.

The treatment was well-tolerated, with manageable grade 3 or 4 toxicities, including neutropenia (8.9%) and diarrhea (6.7%), suggesting it may be a safer alternative compared to conventional chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer. Ogata, Y., Tanaka, T., Akagi, Y., et al.[2021]

In a study of 400 high-risk stage III colon cancer patients receiving chemotherapy, those with the UGT1A1*28 homozygous mutation experienced significantly higher rates of severe hematologic toxicity (50%) compared to those with the UGT1A1*1 homozygous genotype (16.2%).

The -3156G>A UGT1A1 polymorphism was found to be a strong predictor of early severe hematologic toxicity, with a hazard ratio of 8.4 for patients with the A/A genotype compared to the G/G genotype, indicating the importance of genetic testing before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. Côté, JF., Kirzin, S., Kramar, A., et al.[2018]

Citations

1. onclive.com onclive.com/view/cyt-0851-plus-capecitabine-demonstrates-efficacy-in-advanced-ovarian-cancer

CYT-0851 Plus Capecitabine Demonstrates Efficacy in ... The combination of the novel MCT inhibitor CYT-0851 and capecitabine (Xeloda) displayed clinical activity and a tolerable safety profile in patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4279202/

Efficacy of capecitabine-based combination therapy and ... The clinical benefit rate (CBR) was 75.5%. Fifty of effective patients received with capecitabine monotherapy as maintenance therapy. The ORR (CR + PR) was 4%.

3. biospace.com biospace.com/preliminary-ongoing-results-with-cyt-0851-in-combination-with-capecitabine-or-gemcitabine-in-advanced-solid-tumors-show-early-clinical-activity-and-generally-well-tolerated-safety-profile

Preliminary Ongoing Results with CYT-0851 in ... The overall disease control rate in the capecitabine combination was 71.4%. Combination of CYT-0851 with gemcitabine. Five sarcoma patients, two ...

4. businesswire.com businesswire.com/news/home/20231012887827/en/Ongoing-Results-From-a-Dose-Expansion-Cohort-of-CYT-0851-in-Combination-With-Capecitabine-in-Advanced-Platinum-Resistant-Ovarian-Cancer-Show-Promising-Clinical-Activity-and-Generally-Well-Tolerated-Safety-Profile

Ongoing Results From a Dose Expansion Cohort of CYT ... As of the September 26, 2023 data cutoff, 11 patients with advanced ovarian cancer were treated and evaluable in the capecitabine cohort.

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK71165/

Systematic review of the clinical effectiveness and cost ... - NCBI This review concluded that capecitabine combination therapy for breast cancer was more effective (and likely to be cost-effective) than single-agent docetaxel.

6. researchgate.net researchgate.net/publication/376154031_Abstract_LB_A13_Phase_1_dose_expansion_results_of_CYT-0851_a_monocarboxylate_transporter_MCT_inhibitor_in_combination_with_capecitabine_cape_in_platinum-resistant_ovarian_cancer

Abstract LB_A13: Phase 1 dose expansion results of CYT- ... Follow-up in vitro combination studies showed that CYT-0851 synergized with 5-FU to inhibit cancer cell growth. Monotherapy clinical activity of CYT-0851 has ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32950984/

Efficacy and Safety of Capecitabine Alone or in ... Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI ...