NKT3447 for Advanced Cancer

No longer recruiting at 7 trial locations

Overseen By Andrae Vandross, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NiKang Therapeutics, Inc.

Must not be taking: CDK2 inhibitors

Disqualifiers: Curative candidates, Visceral crisis, HIV, 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 tests a new treatment called NKT3447 for individuals with advanced or metastatic solid tumors, which are cancers that have spread and cannot be surgically removed. The first part of the study assesses the treatment's safety and determines the appropriate dose for various cancers, such as ovarian, endometrial, and certain types of breast cancer. The second part targets ovarian cancer resistant to platinum-based treatments, evaluating NKT3447's effectiveness in combating the cancer. Suitable candidates have cancers that have spread, have not responded to standard treatments, and can take oral medications. 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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Will I have to stop taking my current medications?

The trial information does not specify if 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 NKT3447 is likely to be safe for humans?

Research shows that NKT3447 is a new cancer treatment being tested in people. This treatment blocks certain proteins that help cancer cells grow. Since the research is still in the early stages, detailed information about side effects is not yet available. However, these early studies focus on understanding the treatment's safety and determining the right dose.

In these studies, patients with advanced or spreading solid tumors have received NKT3447. As this is the first time NKT3447 is being tested in humans, the main goal is to determine the safe dosage. Researchers closely monitor for any side effects or problems as the dose increases.

The trial is designed to be careful, gradually increasing the dose until the highest tolerable dose is found. This cautious approach ensures that any side effects remain manageable. While specific side effect information is not yet available, the process aims to protect patients as much as possible while assessing the treatment's safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NKT3447 because it offers a novel approach to treating advanced cancer. Unlike typical chemotherapy treatments that kill both cancerous and healthy cells, NKT3447 is designed to selectively target and inhibit specific cancer cell growth pathways. This targeted approach could potentially reduce side effects and improve effectiveness compared to broad-spectrum therapies. Additionally, as an oral medication, NKT3447 provides a more convenient option compared to traditional intravenous cancer treatments, possibly improving patient quality of life during therapy.

What evidence suggests that NKT3447 might be an effective treatment for advanced cancer?

Research has shown that NKT3447 holds promise for treating certain types of cancer. Studies have found that this treatment can slow down or even shrink tumors in cancers with a specific genetic feature, such as CCNE1 amplified ovarian cancer. This suggests that NKT3447 might be effective against cancers with this genetic trait. The current trial includes two treatment arms: a Dose Escalation arm to assess safety and efficacy at increasing dosage levels, and a Dose Expansion arm to determine preliminary antitumor activity. The treatment targets a protein called CDK2, which aids cancer cell growth. By inhibiting this protein, NKT3447 could potentially stop or reduce tumors in patients with advanced solid tumors. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic solid tumors, including various types of cancer such as breast, ovarian, endometrial, stomach, and small cell lung cancer. Specifically looking for participants with CCNE1 amplified ovarian cancer for the expansion phase.

Inclusion Criteria

My cancer type is eligible for the dose escalation study.

My ovarian cancer is resistant to platinum treatment and has cyclin E amplification.

My cancer is advanced, cannot be surgically removed, and has not improved with standard treatments.

Exclusion Criteria

I have previously been treated with CDK2, WEE1, or PKMYT1 inhibitors.

My solid tumor can potentially be cured with surgery, radiation, or chemotherapy.

I still feel side effects from my previous cancer treatment, but they are mild.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluate the safety, tolerability, and pharmacokinetics (PK) to determine the maximum tolerated dose (MTD) and/or preliminary recommended dose for expansion (RDE) of NKT3447 in adults with advanced or metastatic solid tumors

28 days

Dose Expansion

Evaluate the safety, tolerability, pharmacokinetics (PK), and the preliminary antitumor activity of NKT3447 in adult subjects with CCNE1 amplified ovarian cancer at the RDEs selected in Dose Escalation and to determine the preliminary recommended phase 2 dose (RP2D)

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• NKT3447

Trial Overview NKT3447 is being tested to find out its safety and tolerability at different doses (Dose Escalation phase) and to see how well it works against certain cancers like CCNE1 amplified ovarian cancer (Expansion phase).

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 1 Intervention

Dose expansion will include 2 RDEs selected to determine the preliminary antitumor activity and the RP2D.

Group II: Dose Escalation Experimental Treatment 1 Intervention

Dose escalation will assess the safety, efficacy, and PK/PD data of oral dosing NKT3447 at increasing dosage levels to determine the MTD and/or preliminary RDEs.

Who Is Running the Clinical Trial?

NiKang Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

1,000+

Published Research Related to This Trial

The maximum-tolerated dose (MTD) of SB-743921 was established at 4 mg/m², with neutropenia being the most common dose-limiting toxicity observed in a study involving 44 patients with advanced solid tumors or relapsed/refractory lymphoma.

One patient experienced a durable objective response lasting 11 months, and 6 patients had stable disease for over four treatment cycles, indicating promising efficacy and a favorable safety profile for further development of SB-743921.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A first in human study of SB-743921, a kinesin spindle protein inhibitor, to determine pharmacokinetics, biologic effects and establish a recommended phase II dose. Holen, KD., Belani, CP., Wilding, G., et al.[2021]

In a study of 1864 advanced ovarian cancer patients, 71% experienced neurotoxicity (NT) during treatment, particularly affecting older patients and those with lower quality of life scores.

Switching from paclitaxel to docetaxel did not show any significant improvement in NT symptoms, with similar rates of worsening NT reported for both drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotoxicity in ovarian cancer patients on Gynecologic Oncology Group (GOG) protocol 218: characteristics associated with toxicity and the effect of substitution with docetaxel: an NRG Oncology/Gynecologic Oncology Group study. Chase, DM., Huang, H., Foss, CD., et al.[2018]

In a study of 1,012 cancer patients, 10% had PIK3CA mutations, and those with the H1047R mutation showed a significantly higher partial response rate (38%) to PI3K/AKT/mTOR inhibitors compared to other mutation types and wild-type patients.

Patients with coexisting PIK3CA and KRAS mutations did not achieve any partial responses, indicating that the presence of KRAS mutations may negatively impact the efficacy of these targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Janku, F., Wheler, JJ., Naing, A., et al.[2022]

The combination of NVP-BEZ235, a dual PI3K/mTOR inhibitor, and sunitinib, a tyrosine kinase inhibitor, significantly enhances the antitumor effect in castration-resistant prostate cancer (CRPC) cells that are resistant to docetaxel, with a strong synergy indicated by a synergy volume of 182.47 μM/ml2%.

This combination therapy not only reduced the IC50 values of both drugs by 7.8-fold for NVP-BEZ235 and 6.6-fold for sunitinib but also induced caspase-dependent apoptosis in the resistant cancer cells, suggesting a promising strategy for overcoming treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic antitumor effect of NVP-BEZ235 and sunitinib on docetaxel-resistant human castration-resistant prostate cancer cells. Park, HS., Hong, SK., Oh, MM., et al.[2018]

In a phase I study involving 38 patients with various malignancies, NKT-01 (deoxyspergualin) was administered intravenously, showing no clear adverse effects at single doses up to 320 mg/m2, but dose-dependent toxicities such as myelosuppression and nausea were observed during daily administration.

A significant reduction in leukemic cells was noted in one patient with adult T-cell leukemia, suggesting potential efficacy, while the recommended dose for further studies was set at 400 mg/m2 for solid tumors, indicating a need for careful monitoring of hematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of NKT-01. Tamura, K., Niitani, H., Oguro, M., et al.[2018]

In a study of 307 triple-negative breast cancer (TNBC) patients, high levels of nuclear KIFC1 (nKIFC1) were linked to significantly worse survival outcomes specifically in African American patients, indicating its potential as a prognostic biomarker for this group.

The study found that nKIFC1 expression correlated with cell proliferation in White TNBC patients but not in African American patients, suggesting that nKIFC1 may play a different role in tumor behavior and migration in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional study of nuclear KIFC1 as a biomarker of poor prognosis in African American women with triple-negative breast cancer. Ogden, A., Garlapati, C., Li, XB., et al.[2022]

The dual PI3K/mTOR inhibitor PF-04691502 showed over 80% inhibition of cell growth in five nasopharyngeal carcinoma (NPC) cell lines, indicating strong preclinical efficacy with IC50 values in the hundred nanomolar range.

In vivo studies demonstrated that PF-04691502 effectively reduced tumor volume and weight in a xenograft model without significant body weight loss, suggesting it is both effective and well-tolerated for potential NPC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of the PI3K-mTOR dual inhibitor PF-04691502 as a novel therapeutic drug in nasopharyngeal carcinoma. Wong, CH., Loong, HH., Hui, CW., et al.[2022]

The combination of EPI-002, an antagonist targeting the N-terminal domain of the androgen receptor, with mTOR inhibitors like BEZ235 showed significant antitumor activity in enzalutamide-resistant prostate cancer cells, indicating a promising therapeutic strategy for castration-resistant prostate cancer (CRPC).

This dual targeting approach effectively reduced the expression of AR-V target genes and inhibited tumor growth in both in vitro and in vivo models, suggesting that blocking both the androgen receptor and the PI3K/Akt/mTOR pathway can enhance treatment efficacy in advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cotargeting Androgen Receptor Splice Variants and mTOR Signaling Pathway for the Treatment of Castration-Resistant Prostate Cancer. Kato, M., Banuelos, CA., Imamura, Y., et al.[2022]

The study found that an oral drug combining paclitaxel and HM30181A is well tolerated in patients with advanced cancers, with only one case of significant toxicity (grade 3 neutropenia) reported at a dose of 240 mg/m².

The recommended phase II dose for this combination therapy is 300 mg/m² of paclitaxel, which effectively achieves the desired plasma concentration for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer. Lee, HJ., Heo, DS., Cho, JY., et al.[2021]

In a phase I study involving 43 patients with advanced solid tumors, MEDI-573 demonstrated a favorable safety profile with no dose-limiting toxicities and only one case of treatment-related hyperglycemia.

While MEDI-573 did not lead to any partial or complete responses in the tumors, 13 out of 39 evaluable patients showed stable disease, indicating some preliminary antitumor activity in a heavily pretreated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Haluska, P., Menefee, M., Plimack, ER., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06264921

A Study With NKT3447 for Adults With Advanced/Metastatic ... This is a Phase 1/1b, first-in-human, open-label, multicenter study of NKT3447 in adults with advanced/ metastatic solid tumors.

2. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/5705/741749/Abstract-5705-Discovery-of-a-selective-slow-off

Discovery of a selective slow-off CDK2 inhibitor NKT3447 with ... Furthermore, NKT3447 treatment results in a dose-dependent tumor growth inhibition or tumor regression in CCNE1 amplified OVCAR3 and MKN1 tumor ...

3. ctv.veeva.com ctv.veeva.com/study/a-phase-1-first-in-human-study-with-nkt3447-for-adults-with-advanced-metastatic-solid-tumors

A Study With NKT3447 for Adults With Advanced/Metastatic ... This is a Phase 1/1b, first-in-human, open-label, multicenter study of NKT3447 in adults with advanced/ metastatic solid tumors. The study ...

4. trial.medpath.com trial.medpath.com/clinical-trial/87f817f7961c6d15/safety-tolerability-pk-cdk2-inhibitor-nkt3447

A Study with NKT3447 for Adults with Advanced/Metastatic ... This is a Phase 1/1b, first-in-human, open-label, multicenter study of NKT3447 in adults with advanced/ metastatic solid tumors. The study consists of 2 parts, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12477701/

Targeting CDK2 for cancer therapy - PMC A Study with NKT3447 for Adults with Advanced/Metastatic Solid Tumors (NCT06264921), phase 1/2 study of NKT3447 for advanced/metastatic cancers that have ...