M-CENK + N-803 + Gemcitabine for Ovarian Cancer

Overseen By Paula Bradshaw

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: ImmunityBio, Inc.

Must not be taking: Immunotherapy, Corticosteroids, Antiretrovirals, others

Disqualifiers: Metastasis, Transplant, Autoimmune, 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: 13

Duration: Varies

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there is a requirement to not have anti-tumor chemotherapy or investigational agents within 2 weeks before the M-CENK cell infusion, and no immunotherapy within 4 weeks prior. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug M-CENK + N-803 + Gemcitabine for ovarian cancer?

Research shows that gemcitabine, a component of the treatment, has been studied for its effectiveness in treating recurrent ovarian cancer, demonstrating some positive outcomes in terms of response rate and progression-free survival. ^{1 2 3 4 5}

Is the treatment M-CENK + N-803 + Gemcitabine generally safe in humans?

The safety of gemcitabine, a part of the treatment, has been studied in various cancers, showing it can be safely used with other drugs, though it may have side effects. However, specific safety data for the combination of M-CENK, N-803, and gemcitabine is not available in the provided research. ^{3 4 5 6 7}

What makes the M-CENK + N-803 + Gemcitabine treatment unique for ovarian cancer?

The M-CENK + N-803 + Gemcitabine treatment is unique because it combines an immune-based therapy (M-CENK) with a cytokine (N-803) and a chemotherapy drug (Gemcitabine), potentially enhancing the immune system's ability to fight ovarian cancer while also targeting cancer cells directly. ^{3 8 9 10 11}

What is the purpose of this trial?

This is phase 2 single arm study evaluating the safety and preliminary efficacy of M-CENK adoptive cell therapy and fixed dose of N-803 in combination with gemcitabine in participants with platinum-resistant high-grade ovarian cancer (HGOC).Up to 20 participants will receive M-CENK (IV) and N-803 (SC) in combination with gemcitabine (IV). Participants will undergo an apheresis procedure for the collection of mononuclear cells (MNCs) at least 1 day prior to Cycle 1 for manufacturing of M-CENK. Starting in Cycle 1, participants will receive gemcitabine and starting in Cycle 2 they will also receive M-CENK and N-803, until no additional M-CENK is available or confirmed PD per iRECIST, unless the participant is potentially deriving benefit per Investigator's assessment. Participants who complete the study treatment or discontinue study treatment will be followed for survival/disease status every 12 weeks (± 2 weeks) for up to 12 months after the last study treatment or until death, lost to follow-up, or withdrawal of consent.

Research Team

Leonard Sender, MD

Principal Investigator

ImmunityBio, Inc.

Eligibility Criteria

This trial is for up to 20 individuals with high-grade ovarian cancer that has not responded to platinum-based chemotherapy. Participants must undergo a procedure to collect immune cells before starting treatment and can continue receiving the therapy unless their disease progresses or they no longer benefit from it, as determined by the study doctor.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

I had cancer before, but it won't affect this treatment's safety or results.

Must have at least one lesion that meets the definition of measurable disease defined by RECIST v1.1 criteria

Exclusion Criteria

My cancer has spread beyond my abdominal area.

Receiving any other investigational agents

I have another cancer that is getting worse or needs treatment now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis

Participants undergo an apheresis procedure for the collection of mononuclear cells (MNCs) for manufacturing of M-CENK

1 day

1 visit (in-person)

Treatment

Participants receive gemcitabine starting in Cycle 1 and M-CENK and N-803 starting in Cycle 2, until no additional M-CENK is available or confirmed PD per iRECIST

Varies

Follow-up

Participants are monitored for survival/disease status every 12 weeks for up to 12 months after the last study treatment

12 months

Every 12 weeks (± 2 weeks)

Treatment Details

Interventions

• M-CENK
• N-803

Trial Overview The trial tests a combination of treatments: M-CENK adoptive cell therapy (given intravenously), N-803 (an IL-15 superagonist given subcutaneously), and gemcitabine (also given intravenously). The goal is to evaluate safety and how well this approach works in treating ovarian cancer that's resistant to standard therapies.

Participant Groups

Group I: All subjects Experimental Treatment 3 Interventions

Gemcitabine plus M-CENK plus N-803

Who Is Running the Clinical Trial?

ImmunityBio, Inc.

Lead Sponsor

Trials

75

Recruited

5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Findings from Research

In a Phase II study involving 22 patients with recurrent epithelial ovarian cancer, gemcitabine combined with platinum chemotherapy showed a response rate of 36.4%, with a median survival time of 10 months, indicating its potential effectiveness even in platinum-resistant cases.

While the treatment was generally well-tolerated, 81.8% of patients experienced side effects, with significant occurrences of anemia and neutropenia, leading to dose adjustments or delays in treatment for nearly half of the participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of gemcitabine combined with platinum chemotherapy for recurrent epithelial ovarian cancer. Peng, P., Shen, K., Yang, JX., et al.[2022]

The combination of paclitaxel, carboplatin, and gemcitabine was found to be feasible and active in treating previously untreated ovarian cancer, with 10 out of 14 patients showing an objective response.

While the treatment caused significant hematological toxicities, such as neutropenia (76.3%) and leukopenia (70.9%), serious complications like febrile neutropenia were rare (1.8%), indicating that the regimen is manageable and can proceed to further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel, carboplatin, and gemcitabine in previously untreated patients with epithelial ovarian cancer FIGO stage IC-IV (AGO-OVAR protocol OVAR-8). du Bois, A., Belau, A., Wagner, U., et al.[2022]

The combination of weekly intravenous gemcitabine and topotecan was found to be an active treatment for recurrent ovarian cancer, achieving an overall response rate of 20.8% in a study of 24 women, with some patients experiencing complete and partial responses.

The treatment demonstrated a manageable safety profile, with the maximum tolerated dose not reached and only mild to moderate adverse effects, such as neutropenia and fatigue, indicating it could be a viable option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of weekly topotecan and gemcitabine as a salvage treatment in patients with recurrent ovarian cancer: a phase I study. Syrios, J., Kouroussis, C., Kotsakis, A., et al.[2022]

The maximum tolerated dose (MTD) of gemcitabine when combined with gefitinib for patients with advanced pancreatic adenocarcinoma was determined to be 1,200 mg/m², with the treatment being feasible and tolerable.

Toxicity was mainly hematologic, with significant side effects including Grade 3 and 4 granulocytopenia, but no objective responses were observed in the patients, indicating that while the combination is manageable, it may not be effective in improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of fixed dose rate infusion gemcitabine with gefitinib in patients with pancreatic carcinoma. Carneiro, BA., Brand, RE., Fine, E., et al.[2022]

In a study of 43 recurrent epithelial ovarian cancer patients treated with gemcitabine, the overall response rate was modest at 11.6%, with better outcomes in platinum-sensitive patients (19% response) compared to platinum-resistant patients (4.5%).

Combining gemcitabine with platinum-based chemotherapy significantly improved progression-free survival (PFS) to 8.1 months compared to 2.7 months with gemcitabine alone in platinum-sensitive patients, indicating that combination therapy may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes of gemcitabine in refractory or recurrent epithelial ovarian cancer patients. Chanpanitkitchot, S., Tangjitgamol, S., Khunnarong, J., et al.[2022]

In a study of 28 patients with relapsed/refractory soft tissue sarcoma, the combination of fixed dose rate gemcitabine and docetaxel showed an overall response rate of 14.3% and a clinical benefit rate of 53.6%, indicating some effectiveness in this challenging condition.

The treatment was generally well-tolerated, with manageable side effects; the most common severe toxicities were grade 3-4 neutropenia (50%) and anemia (17.9%), but no grade 4 non-hematologic toxicities were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of fixed dose rate gemcitabine infusion in combination with docetaxel in patients with relapsed/refractory soft tissue sarcoma]. Yao, Z., Yang, S., Zhao, Y., et al.[2022]

In a study involving four patients with advanced pancreatic or breast cancer, fixed dose rate gemcitabine administered intravenously was found to be well tolerated, with the main side effect being reversible myelosuppression.

No significant cardiac or renal toxicity was observed, suggesting that iv-FDR gemcitabine could be a safe treatment option worth further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical observations on safety of fixed dose rate gemcitabine chemotherapy by intravenous infusion. Yao, CY., Huang, XE., Tang, JH., et al.[2022]

The study found that fixed-dose rate (FDR) gemcitabine combined with carboplatin is effective in treating platinum-sensitive ovarian cancer, with overall response rates of 38.1% to 58.8% across different treatment arms involving 60 patients.

The maximum tolerated dose (MTD) for FDR gemcitabine was established at 1000 mg/m², and the treatment showed no unusual safety concerns, indicating it is a viable option for patients with relapsed ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose rate gemcitabine plus carboplatin in relapsed, platinum-sensitive ovarian cancer patients: results of a three-arm Phase I study. Alvarez, RD., Mannel, R., García, AA., et al.[2022]

The human ovarian carcinoma cell line AG6000 developed significant resistance to gemcitabine (dFdCyd), with the IC50 increasing from 0.6 nM in the sensitive A2780 line to 92 µM in AG6000, indicating a stable resistance phenotype primarily due to a deficiency in deoxycytidine kinase (dCK).

AG6000 not only showed resistance to gemcitabine but also to other drugs that require dCK for activation, such as 1-beta-D-arabinofuranosylcytosine and 5-aza-2'-deoxycytidine, suggesting a broader mechanism of resistance that does not involve P-glycoprotein induction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and molecular characterization of a 2',2'-difluorodeoxycytidine-resistant variant of the human ovarian carcinoma cell line A2780. Ruiz van Haperen, VW., Veerman, G., Eriksson, S., et al.[2022]

Gemcitabine is an effective cytotoxic agent approved for treating various cancers, including non-small cell lung cancer, pancreatic, bladder, breast, and now ovarian cancer, demonstrating its broad applicability in oncology.

The drug has a favorable safety profile, primarily causing myelosuppression, which makes it a suitable treatment option for elderly and unfit patients, especially when combined with other therapies like cisplatinum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of gemcitabine in cancer therapy. Toschi, L., Finocchiaro, G., Bartolini, S., et al.[2022]

Gemcitabine, while generally considered safe and well-tolerated for treating ovarian cancer, can induce dilated cardiomyopathy, as evidenced by a case report of a 41-year-old woman who developed severe heart failure after treatment.

The patient's heart function improved significantly after stopping gemcitabine and initiating heart failure management, highlighting the importance of recognizing and addressing potential cardiotoxicity from this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-induced dilated-cardiomyopathy in patient with platinum-refractory ovarian-cancer: A case report and literature review. Raimondi, L., Raimondi, FM., Rossi, L., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

Phase II study of gemcitabine combined with platinum chemotherapy for recurrent epithelial ovarian cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel, carboplatin, and gemcitabine in previously untreated patients with epithelial ovarian cancer FIGO stage IC-IV (AGO-OVAR protocol OVAR-8). [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Combination of weekly topotecan and gemcitabine as a salvage treatment in patients with recurrent ovarian cancer: a phase I study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Phase I trial of fixed dose rate infusion gemcitabine with gefitinib in patients with pancreatic carcinoma. [2022]

5. Thailand pubmed.ncbi.nlm.nih.gov

Treatment outcomes of gemcitabine in refractory or recurrent epithelial ovarian cancer patients. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of fixed dose rate gemcitabine infusion in combination with docetaxel in patients with relapsed/refractory soft tissue sarcoma]. [2022]

7. Thailand pubmed.ncbi.nlm.nih.gov

Clinical observations on safety of fixed dose rate gemcitabine chemotherapy by intravenous infusion. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Fixed-dose rate gemcitabine plus carboplatin in relapsed, platinum-sensitive ovarian cancer patients: results of a three-arm Phase I study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Development and molecular characterization of a 2',2'-difluorodeoxycytidine-resistant variant of the human ovarian carcinoma cell line A2780. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Role of gemcitabine in cancer therapy. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Gemcitabine-induced dilated-cardiomyopathy in patient with platinum-refractory ovarian-cancer: A case report and literature review. [2022]