LY2880070 for Cancer

No longer recruiting at 20 trial locations

Overseen By Esperas Pharma Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Esperas Pharma Inc.

Disqualifiers: CNS metastasis, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, LY2880070 (an experimental treatment), combined with Gemcitabine, in individuals with advanced or metastatic solid tumors. It consists of multiple parts to assess how well these drugs work on different cancer types, such as ovarian, breast, and pancreatic cancer. Individuals with these cancers, who have undergone unsuccessful treatments, might be suitable candidates for this trial. The goal is to determine if this new combination can help manage these challenging cancers. 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 information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that LY2880070 is generally well-tolerated when used alone. However, earlier studies reported side effects such as vomiting, nausea, and tiredness in more than 40% of participants.

When combined with Gemcitabine, a chemotherapy drug, LY2880070 remains mostly well-tolerated. Common side effects include tiredness, nausea, vomiting, and diarrhea. These reactions are typical with cancer treatments, and most people manage them well.

This treatment is still under testing to ensure safety and effectiveness. The studies closely monitor for any side effects, providing a safe environment for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LY2880070 in combination with Gemcitabine because it offers a new approach to cancer treatment. Unlike traditional chemotherapy, which often targets rapidly dividing cells indiscriminately, LY2880070 is designed to be more selective in its mechanism. This investigational drug works by inhibiting certain proteins involved in the growth of cancer cells, potentially leading to more effective targeting of the cancer and sparing more healthy cells. The combination with Gemcitabine, a well-known chemotherapy agent, could enhance its effectiveness by attacking the cancer from multiple angles. This dual approach is particularly promising for cancers like ovarian, endometrial, and soft tissue sarcoma, where treatment options are limited.

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

Research has shown that LY2880070 is a promising drug because it targets a protein called CHK1, which aids cancer cells in self-repair. By blocking CHK1, LY2880070 may increase cancer cells' sensitivity to treatment. In this trial, some participants will receive LY2880070 alone, while others will receive it in combination with gemcitabine, a chemotherapy drug. Studies have found that combining LY2880070 with gemcitabine can increase damage to cancer cells' DNA, potentially leading to better treatment outcomes. However, this combination has not been very effective in certain hard-to-treat cancers, such as pancreatic cancer. Overall, the combination might help shrink or stabilize some solid tumors, but further research is needed to confirm its efficacy. ^{1 2 3 6 7}

Who Is on the Research Team?

Email: [e-mail]

Principal Investigator

Esperas Pharma Inc.

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced or metastatic cancers, including colorectal, breast, ovarian, endometrial cancer and sarcomas. Participants must have measurable tumor lesions and adequate organ function. They should not benefit from standard therapy and agree to use contraception. Exclusions include recent investigational drug use, significant radiation exposure to bone marrow, active secondary cancers within a year (with some exceptions), pregnancy or nursing women, CNS metastasis symptoms, certain viral infections or heart rhythm issues.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

You are expected to live for at least 12 weeks.

My organs are functioning well.

Exclusion Criteria

My cancer has spread to my brain and is causing symptoms.

Have received treatment with an investigational drug which has not received regulatory approval within 21 days of first study treatment

Your heart's electrical activity takes longer than normal to reset, or you have a condition that causes your heart to take longer to reset.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple oral doses of LY2880070, with Gemcitabine administered intravenously during 21-day cycles

21-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• LY2880070

Trial Overview The study tests the safety and effectiveness of LY2880070 in combination with Gemcitabine for treating various solid tumors. It's divided into three parts: one focusing on metabolism phenotype related to CYP2D6 enzyme activity; another on specific genetic signatures in high-grade serous ovarian cancer; and the third part assessing broader efficacy across multiple cancer types.

How Is the Trial Designed?

Group I: Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group II: Part B:LY2880070 and Gemcitabine (Ovarian) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group III: Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS)) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group IV: Part B: LY2880070 and Gemcitabine (Pancreatic) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group V: Part B: LY2880070 and Gemcitabine (Endometrial) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group VI: Part B: LY2880070 and Gemcitabine (Colorectal) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group VII: Part B: LY2880070 and Gemcitabine (Breast) Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Group VIII: Part A: LY2880070 with Gemcitabine Experimental Treatment 2 Interventions

Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles

Group IX: Part A: LY2880070 (Metabolism Phenotype) Experimental Treatment 1 Intervention

Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers

Group X: Part A: LY2880070 Experimental Treatment 1 Intervention

Multiple oral doses of LY2880070 during 21-day cycles

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Esperas Pharma Inc.

Lead Sponsor

Trials

1

Recruited

230+

Published Research Related to This Trial

Gemcitabine is an effective treatment for various solid tumors, including non-small-cell lung cancer and pancreatic cancer, with promising results also seen in breast and bladder cancers, based on phase II studies.

The drug has a favorable side-effect profile and may enhance the effectiveness of other DNA-damaging agents, suggesting its potential for use in combination therapies and different treatment schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of gemcitabine in the treatment of other tumours. Carmichael, J.[2022]

Gemcitabine (2',2'-Difluorodeoxycytidine) shows significant antitumor activity against various human tumors, with a study evaluating 215 tumor specimens revealing a concentration-dependent increase in tumor inhibition, particularly at higher doses (up to 200 micrograms/ml).

The agent demonstrated effectiveness across multiple cancer types, including colorectal, breast, lung, ovarian, kidney, and melanoma, suggesting it should be further tested in Phase II clinical trials targeting these malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of 2',2'-difluorodeoxycytidine (Gemcitabine) against human tumor colony forming units. Hanauske, AR., Degen, D., Marshall, MH., et al.[2022]

In a late phase II study involving 73 patients with untreated non-small-cell lung cancer (NSCLC), LY188011 (gemcitabine hydrochloride) demonstrated an efficacy response rate of 26%, indicating it can be a viable treatment option for this type of cancer.

The safety profile of LY188011 was generally favorable, with most adverse reactions being mild (grade 1 or 2), although careful monitoring is necessary due to a reported death from interstitial pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Late phase II study of LY188011 (gemcitabine hydrochloride) in patient with non-small-cell lung cancer. Gemcitabine Late Phase II Cooperative Study Group A)]. Fukuoka, M., Negoro, S., Kudo, S., et al.[2022]

Gemcitabine is a highly valuable chemotherapeutic agent for treating both early and advanced non-small cell lung cancer (NSCLC), showing a tumor regression rate of about 20% in patients, regardless of their previous chemotherapy history.

It is particularly effective in combination with platinum-based therapies and can be safely administered alongside radiotherapy, making it a key component in multimodal treatment strategies for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine (Gemzar) in non-small cell lung cancer. Manegold, C.[2022]

Gemcitabine, a nucleoside analogue, shows promise in treating non-small cell lung cancer (NSCLC) and has been evaluated in economic studies across multiple countries, indicating it may be cost-effective compared to other treatments.

The economic evaluations suggest that gemcitabine can be administered safely in an outpatient setting with a lower side-effect profile, which contributes to its potential cost savings in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the pharmacoeconomic research on gemcitabine in the treatment of advanced non-small cell lung cancer. Minshall, ME., Liepa, AM.[2022]

In a Phase I study involving 13 Japanese patients with advanced solid tumors, LY2334737 was found to be tolerable at doses up to 30 mg/day, but the 40 mg/day dose led to significant dose-limiting toxicities, including severe liver issues and thrombocytopenia.

Two patients on the 30 mg/day dose achieved stable disease for 135 and 155 days, indicating some antitumor activity, but the study suggests that alternative dosing schedules may be needed to manage the toxicities observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of oral gemcitabine prodrug (LY2334737) in Japanese patients with advanced solid tumors. Yamamoto, N., Nokihara, H., Yamada, Y., et al.[2022]

The maximum tolerated dose (MTD) of LY2334737, an oral prodrug of gemcitabine, was determined to be 40 mg, with fatigue and elevated liver enzymes identified as the most common dose-limiting toxicities in a study involving 65 patients with advanced cancer.

The study showed promising signs of antitumor activity, with one patient achieving a complete response and 22 patients maintaining stable disease, indicating that further development of LY2334737 is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of Oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients with advanced solid tumors. Koolen, SL., Witteveen, PO., Jansen, RS., et al.[2022]

LY188011 (Gemcitabine hydrochloride) was found to have a maximum tolerated dose (MTD) of 1,000 mg/m2, with myelosuppression being the main dose-limiting factor observed in a Phase I study involving multiple patients.

The treatment showed anti-cancer effects in some patients with gastric and colon cancers, and the recommended dosing schedule for further studies is 800 mg/m2 weekly for 3 weeks, followed by a week of rest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. Taguchi, T., Furuse, K., Fukuoka, M., et al.[2022]

LY 188011 (gemcitabine hydrochloride) demonstrated significant antitumor effects in seven out of fifteen human tumor xenograft models in nude mice, including drug-resistant colorectal and lung cancers.

Compared to mitomycin C, LY 188011 was more effective in two lung cancer models and caused fewer side effects, indicating its potential as a promising candidate for clinical cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antitumor activity of LY 188011, a new deoxycytidine analog, against human cancers xenografted into nude mice]. Fujita, M., Fujita, F., Inaba, H., et al.[2022]

Gemcitabine (GEMZAR) has shown to be an effective treatment for non-small-cell lung cancer (NSCLC) with a response rate of about 21% as a single agent, and it has a mild toxicity profile, making it suitable for combination therapies.

When combined with cisplatin, gemcitabine achieved higher response rates ranging from 38% to 54% and median survival times of 8.4 to 14.3 months, with manageable side effects, indicating its potential as a preferred treatment option in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. Steward, WP.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37819936/

A Phase I Expansion Cohort Study Evaluating the Safety and ... Conclusions: No evidence of clinical activity was observed for combined low-dose gemcitabine and LY2880070 in this treatment-refractory PDAC ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02632448

NCT02632448 | A Study of LY2880070 in Participants With ... The main purpose of this 3-part study is to evaluate the safety and efficacy of the study drug known as LY2880070 in participants with advanced or metastatic ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT292725

A phase Ib study of oral Chk1 inhibitor LY2880070 in ... Chk1 inhibitors are known to increase the anti-tumor efficacy of agents such as gemcitabine (GEM), which induce replication stress. Synergy between these two ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10842136/

A Phase 1 Expansion Cohort Study Evaluating the Safety ... LY2880070 is a highly potent CHK1 inhibitor with half maximal inhibitory concentration (IC50) of 0.5 nM. A phase 1 trial of LY2880070 monotherapy demonstrated ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3579

A phase Ib study of oral Chk1 inhibitor LY2880070 as ... Methods: This 2-part, open-label multi-center study explores the safety, pharmacokinetics (PK) and anti-tumor activity of LY in patients with ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02516-9/fulltext

537P A phase I/II study of oral chk1 inhibitor LY2880070 in ... This two-part, open-label, multi-center study explored the safety, pharmacokinetics (PK), and anti-tumor activity of LY in patients with advanced or metastatic ...

7. synapse.patsnap.com synapse.patsnap.com/drug/ce129d0aebf54db4bcdaddb39c0bb39d

LY-2880070 - Drug Targets, Indications, Patents By blocking Chk1, these inhibitors can induce DNA damage and prevent cancer cells from repairing their DNA, ultimately leading to cell death. Chk1 inhibitors ...