Iadademstat + Paclitaxel for Lung Cancer

No longer recruiting at 2 trial locations

Overseen By Tanu singh

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: LSD1 inhibitors

Disqualifiers: More than 3 therapies, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, iadademstat (an experimental treatment also known as ORY-1001) and paclitaxel, for individuals with specific types of advanced neuroendocrine cancers, including small cell lung cancer (SCLC). The goal is to evaluate the effectiveness of these drugs together, particularly for patients whose cancer has returned or resisted other treatments. Suitable candidates for this trial are those previously treated with certain chemotherapy drugs and have cancers that include a high-grade neuroendocrine or small cell component. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take medications with LSD1 inhibitory activity (like tranylcypromine or phenelzine) within 3 weeks of starting the trial. It's best to discuss your current medications with the trial team.

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

Research shows that iadademstat, when combined with paclitaxel, is generally safe for treating certain cancers. Earlier studies have demonstrated promising safety results for iadademstat, particularly in patients with acute myeloid leukemia (AML) and other cancers. Paclitaxel, another drug in this trial, has been safely used for lung cancer and is often combined with other medications to reduce side effects.

This is a Phase II trial, indicating that some safety information is already available. Both drugs have been well-tolerated in past studies. However, like any treatment, side effects such as tiredness or nausea can occur, which are common in cancer treatments. Participants should discuss any concerns with the trial team to determine if joining is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lung cancer?

Researchers are excited about Iadademstat combined with Paclitaxel for lung cancer because it offers a fresh approach to treatment. Iadademstat is a new type of drug that works by inhibiting a specific enzyme, LSD1, which plays a role in the growth of cancer cells. This mechanism is different from traditional chemotherapy drugs, like Paclitaxel, which focus on stopping cell division. By targeting LSD1, Iadademstat could potentially slow down the cancer's progression in a novel way, offering hope for more effective treatment outcomes. Additionally, combining it with Paclitaxel leverages the strengths of both drugs, potentially enhancing their overall effectiveness against lung cancer.

What evidence suggests that Iadademstat plus Paclitaxel could be an effective treatment for lung cancer?

Research has shown that combining iadademstat with paclitaxel might effectively treat small cell lung cancer (SCLC) and some neuroendocrine cancers. In this trial, participants will receive both iadademstat and paclitaxel. Paclitaxel alone has shown promise, with response rates of up to 41% in other lung cancers. Iadademstat blocks a protein called LSD1, which can influence cancer growth. This combination aims to be more effective by attacking cancer cells directly and disrupting their growth. Early studies in labs and animals have supported this approach, showing positive results in slowing cancer progression. ^{1 2 4 6 7}

Who Is on the Research Team?

Namrata Vijavergia

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain types of advanced cancers, including relapsed/refractory SCLC and high-grade extrapulmonary neuroendocrine carcinomas. Participants must have had platinum-based chemo but no taxane therapy unless it was over six months prior as neoadjuvant/adjuvant treatment. They should be able to swallow pills, not have severe infections or other health conditions that could interfere with the study, and agree to use effective contraception.

Inclusion Criteria

I can swallow pills and keep them down.

I am a male willing to follow strict rules for preventing pregnancy during and 6 months after the study.

I've had platinum-based chemo and up to 3 treatments for advanced cancer, but no taxane unless it was over 6 months ago.

Exclusion Criteria

I am not allergic to iadademstat, paclitaxel, or their ingredients.

I haven't had taxane-based treatments for my condition in the last 6 months, except as part of early cancer treatment.

I have not had surgery or significant injury within the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

A safety lead-in phase with 12 patients to assess initial safety and tolerability

6 weeks

Weekly visits for treatment and monitoring

Treatment

Participants receive iadademstat and paclitaxel in a 21-day cycle with weekly administration

2 years

Weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Iadademstat
• Paclitaxel

Trial Overview The trial tests iadademstat combined with weekly paclitaxel in patients who've seen their cancer return or resist previous treatments. It's a phase II study involving two groups: one with small cell lung cancer (SCLC) and another with grade 3 neuroendocrine carcinomas (G3 NEC), each having 21 patients.

How Is the Trial Designed?

Group I: Iadademstat plus Paclitaxel Experimental Treatment 2 Interventions

Iadademstat oralon a 5 day ON and 2-day OFF schedule every week plus Paclitaxel administered intravenously weekly on day 1, 8 and 15 on day 1 of a 21 day treatment cycle.

Iadademstat is already approved in United States, European Union for the following indications:

Approved in United States as Iadademstat for:

• Orphan drug designation for Acute Myeloid Leukemia (AML)

Approved in European Union as Iadademstat for:

• Orphan drug designation for Acute Myeloid Leukemia (AML)

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Oryzon Genomics S.A.

Industry Sponsor

Trials

5

Recruited

350+

Published Research Related to This Trial

Paclitaxel has demonstrated strong antitumor activity in various cancers, including ovarian, breast, and lung carcinoma, especially when combined with platinum compounds like cisplatin and carboplatin.

Recent large randomized trials in Europe have explored the effectiveness of paclitaxel in combination with platinum for treating non-small cell lung cancer, showing promising results and leading to ongoing studies on its use in preoperative settings and with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer. Novello, S., Le Chevalier, T.[2019]

Paclitaxel (TAXOL) has shown promising efficacy in treating lung cancer, with objective response rates of 21% and 24% in patients with non-small cell lung cancer, and a higher response rate of 34% in patients with extensive-stage small cell lung cancer.

Further research is necessary to explore the effectiveness of paclitaxel as a standalone treatment for small cell lung cancer and its potential as a radiosensitizer or in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of paclitaxel (Taxol) in advanced lung cancer. Ettinger, DS.[2015]

The combination of paclitaxel and vinorelbine was effective as a first-line treatment for untreated patients with metastatic lung adenocarcinoma, with a response rate of 50% and a median survival of 10 months based on a study of 54 patients.

While myelotoxicity was a common side effect affecting 87% of patients, severe neutropenia (grade 4) occurred in only 14.8%, indicating that the treatment regimen was manageable and did not require dose reductions for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and vinorelbine combination in advanced inoperable adenocarcinoma of the lung: a phase II study. Stathopoulos, GP., Veslemes, M., Georgatou, N., et al.[2018]

Paclitaxel is an effective treatment for stages III and IV small cell and non-small cell lung cancer, showing comparable activity to other available agents, whether administered as a single agent or in combination therapies.

In combination therapy, paclitaxel with cisplatin has demonstrated superior efficacy compared to etoposide with cisplatin for non-small cell lung cancer, indicating its potential as a preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination paclitaxel and platinum in the treatment of lung cancer: US experience. Bunn, PA.[2015]

In a study of 33 patients with progressive or recurrent non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, Abraxane showed a partial response rate of 33.3%, with better outcomes in patients with squamous cell carcinoma (41.7% response) compared to those with adenocarcinoma (21.1%).

The treatment demonstrated a disease control rate of 75.8% and a median progression-free survival of five months, with manageable side effects, indicating that Abraxane is a potentially effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. Yuan, DM., Lv, YL., Yao, YW., et al.[2019]

Paclitaxel, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[2015]

In a study of 599 chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC), the combination of paclitaxel and cisplatin showed superior survival rates compared to the standard etoposide and cisplatin regimen, with a median survival of 9.9 months versus 7.6 months, respectively.

While both regimens had similar toxicity profiles, the low-dose paclitaxel regimen was associated with increased granulocytopenia, and the high-dose regimen showed potential for increased neurotoxicity and cardiac events, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. Bonomi, P., Kim, K., Fairclough, D., et al.[2022]

Single-agent paclitaxel shows a notable 35% to 40% one-year survival rate in patients with advanced metastatic non-small cell lung cancer (NSCLC), indicating its efficacy as a cytotoxic agent.

Combination therapies involving paclitaxel, particularly with adjusted administration schedules, can improve response rates and reduce severe side effects like neutropenia, making it a viable option for patients who cannot tolerate platinum-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent paclitaxel and paclitaxel/non-platinum combination therapy in advanced non-small cell lung cancer. Socinski, MA., Langer, CJ.[2022]

Paclitaxel has shown significant efficacy in treating advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with response rates of 20-25% in NSCLC and over 50% in SCLC, along with median survival times of approximately 40 weeks and 10 months, respectively.

When combined with cisplatin or carboplatin, paclitaxel increases response rates in advanced NSCLC to 39-42% and slightly improves median survival times, demonstrating its potential as a more effective treatment option compared to single-agent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining the role of paclitaxel in lung cancer: summary of recent studies and implications for future directions. Bunn, PA.[2015]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10370

Iadademstat and Paclitaxel for the Treatment of Relapsed ... Giving iadademstat together with paclitaxel may be more effective at treating patients with relapsed or refractory small cell lung cancer and extrapulmonary ...

2. oryzon.com oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-nci-sponsored-phase-iii-clinical-trial

ORYZON announces first patient dosed in NCI-sponsored ... The first patient has been dosed in a Phase I/II trial of iadademstat, Oryzon's potent and selective LSD1 inhibitor, in combination with immune checkpoint ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03689-X/fulltext

1204TiP Iadademstat in combination with paclitaxel in ... Iada and other LSD1is are effective in in vitro and in vivo models of SCLC by preventing INSM1 recruitment of LSD1 which results in NOTCH signaling activation, ...

4. withpower.com withpower.com/trial/phase-2-neuroendocrine-carcinomas-7-2022-787eb

Iadademstat + Paclitaxel for Lung Cancer Paclitaxel has shown effectiveness in treating lung cancer, with studies reporting response rates of up to 41% in non-small cell lung cancer. It is often used ...

5. oryzon.com oryzon.com/en/programs/iadademstat

Iadademstat The good safety profile of iadademstat makes it a good candidate for therapeutic combinations in different cancers like leukemia or some solid tumors. In a ...

6. curetoday.com curetoday.com/view/a-phase-1-trial-of-iadademstat-plus-vidaza-has-dosed-a-patient-with-mds

A Phase 1 Trial of Iadademstat Plus Vidaza Has Dosed ... Iadademstat has shown promising results in AML trials, demonstrating safety ... lung cancer, neuroendocrine tumors and medulloblastoma. Ongoing ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03689-X/pdf

refractory small cell lung carcinoma (SCLC) Iadademstat in combination with paclitaxel in relapsed/ refractory small cell lung carcinoma (SCLC) and extrapulmonary high grade neuroendocrine carcinoma.