NB004 for Solid Tumors
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Ningbo Newbay Technology Development Co., Ltd
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests NB004, a new cancer drug, in patients with advanced, metastatic solid tumors who have no other treatment options. It aims to find the highest safe dose and see if the drug can help shrink tumors.
Is the drug NB004 a promising treatment for solid tumors?The information provided does not mention NB004 or its effects on solid tumors, so we cannot determine if it is a promising treatment based on the given research articles.1361014
What data supports the idea that NB004 for Solid Tumors is an effective treatment?The available research does not provide specific data on the effectiveness of NB004 for Solid Tumors. Instead, it focuses on other treatments like nab-paclitaxel and vinorelbine for different types of cancer, such as breast cancer and lung cancer. Without direct evidence or comparison to other treatments for solid tumors, we cannot conclude the effectiveness of NB004 for this condition based on the provided information.247911
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had any prior anti-cancer therapy within 2 weeks or at least 5 half-lives, whichever is longer, up to a maximum of 3 weeks, before the first dose.
What safety data exists for NB004 treatment in solid tumors?The provided research does not directly mention safety data for NB004 or its alternative names in solid tumors. However, it discusses bispecific antibodies (BsAbs) and their adverse effects in general. BsAbs, like the B7-H4/CD3-bispecific antibody, are being evaluated in clinical trials for solid tumors, but specific safety data for NB004 is not detailed in the given research.58121315
Eligibility Criteria
This trial is for adults (18+) with advanced solid tumors lacking standard treatment options. Participants must have a performance status indicating they are fully active or restricted in physically strenuous activity but ambulatory, measurable disease, and an expected lifespan of at least 12 weeks. They should not have had cancer therapy within the last 2-3 weeks and must not be pregnant or planning pregnancy.Inclusion Criteria
My advanced cancer has no standard treatment options.
I am fully active or can carry out light work.
My cancer has a KRAS G12C mutation.
My cancer can be measured or seen on tests.
Exclusion Criteria
I am not pregnant, breastfeeding, nor planning to become pregnant soon.
I still have side effects from past cancer treatments.
I do not have active infections like hepatitis B, C, or HIV.
My cancer has spread to my brain, spinal cord, or the lining of my brain and spinal cord.
I have been treated with a PIM kinase inhibitor before.
I haven't had cancer treatment in the last 2 weeks or within 5 half-lives of the drug.
Treatment Details
The study tests NB004 tablets as a single agent or combined with other therapies in patients with advanced solid tumors. It's an early-phase trial (Phase 1) focusing on safety, how well the body tolerates it, and how the drug behaves inside the body (pharmacokinetics).
1Treatment groups
Experimental Treatment
Group I: NB004Experimental Treatment1 Intervention
Part1: Dose escalation phase of study drug NB004 monotherapy:
Part 2: Dose Escalation Phase for the NB004 in combination with Sotorasib:
Part 3: COMBO Dose Expansion Phase for the NB004 in combination with Sotorasib:
Find a clinic near you
Research locations nearbySelect from list below to view details:
The University of Texas MD Anderson Cancer CenterHouston, TX
Providence Cancer InstitutePortland, OR
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Who is running the clinical trial?
Ningbo Newbay Technology Development Co., LtdLead Sponsor
References
Inhibition of cell growth by NB1011 requires high thymidylate synthase levels and correlates with p53, p21, bax, and GADD45 induction. [2023]NB1011, a phosphoramidate derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine, is a novel small molecule anticancer agent. NB1011 is selectively active against tumor cells expressing high levels of thymidylate synthase (TS), a critical enzyme in DNA biosynthesis. NB1011 is different from the current TS-targeted drugs, which require inhibition of TS to be effective, because NB1011 cytotoxicity depends upon activation by TS. Here we report a dose-dependent, antitumor activity of NB1011 against established Tomudex-resistant breast cancer (MCF7TDX) xenografts in athymic mice. Against 5-fluorouracil-resistant colon carcinoma (H630R10) xenografts, NB1011 was as efficacious as irinotecan, a drug recently approved for the treatment of 5-fluorouracil-resistant colon cancer. To gain insight into the mechanisms NB1011 uses to suppress cellular growth, we analyzed the downstream molecular events in the high TS-expressing MCF7TDX and RKOTDX cell lines upon NB1011 treatment. NB1011 treatment increased the mRNA levels of p21, Bax, and GADD45. Furthermore, NB1011 induced p53, p21, and Bax proteins specifically in high TS-expressing tumor cells, whereas no induction was observed in low TS-expressing tumor cells (MCF7) or normal cells (WI38). Cell cycle analysis demonstrated that NB1011 treatment of MCF7TDX and RKOTDX cells resulted in an accumulation of cells in the G2-M phase of the cell cycle. Altogether, our data indicate that the induction of the p53 target genes p21, bax, and GADD45, with a concomitant deregulation of the cell cycle, may represent one of the mechanisms by which NB1011 exerts its growth-suppressive effects.
[Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes]. [2018]To assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.
CARP-1 functional mimetics are novel inhibitors of drug-resistant triple negative breast cancers. [2018]Doxorubicin and Cisplatin are the frontline therapeutics for treatment of the triple negative breast cancers (TNBCs). Emergence of drug-resistance often contributes to failure of drugs and poor prognosis, and thus necessitates development of new and improved modalities to treat TNBCs. We generated and characterized chemotherapy-resistant TNBC cells following their culture in chronic presence of Doxorubicin or Cisplatin, and tested whether their viabilities were inhibited by a novel class of CARP- 1 functional mimetic (CFM) compounds. Analogs of parent compound CFM-4 were obtained through structure-activity based medicinal chemistry studies. CFM-4.16, a novel analog of CFM-4, caused superior inhibition of viability of TNBC cells when used in combination with doxorubicin. Doxorubicin and cisplatin inhibited viabilities of parental cells with GI50 dose of 0.02-0.1 μM and 1.65 μM, respectively. The GI50 dose of doxorubicin for doxorubicin-resistant TNBC cells was ≥ 10.0 μM. For Cisplatin-resistant cells, the GI50 dose of Cisplatin was ≥ 6-15.0 μM for MDA-MB-468 sublines and ≥ 150.0 μM for MDA-MB-231 sublines. CFM-4.16 inhibited viability of chemotherapy-resistant TNBC cells, in part by inhibiting oncogenic cMet activation and expression, stimulating CARP-1 expression, caspase-8 cleavage and apoptosis. CFM-4.16 pretreatment enhanced anti-TNBC efficacies of inhibitors of cMET (Tevatinib) or cSrc (Dasatinib). CFM-4.16 suppressed growth of resistant TNBC cells in soft agar as well as in three-dimensional suspension cultures derived from enriched, stem-like cells. Finally, a nanolipid formulation of CFM-4.16 in combination with doxorubicin had superior efficacy in inhibiting TNBC xenograft growth. Our findings collectively demonstrate therapeutic potential of CFM-4.16 for parental and drug-resistant TNBCs.
Phase I Study of Triweekly Nab-Paclitaxel Combined with S-1 in Patients with HER2-negative Metastatic Breast Cancer. [2017]We conducted a phase I study to determine the maximum tolerated dose (MTD) and recommended dose (RD) of triweekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and S-1 combination therapy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC).
[Adverse effects of immune checkpoint inhibitors used to treat melanoma and other cancer]. [2017]Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers and metastatic renal cancer. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events that may be life threatening if not anticipated and managed appropriately. This new family of dysimmune toxicities remains largely unknown to the broad oncology community. We propose here some practical guidelines for the oncologist to help in the clinical care of patients under immune checkpoint molecules.
Preclinical and clinical development of palbociclib and future perspectives. [2018]Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib.
A phase I/II trial of olaparib tablet in combination with eribulin in Japanese patients with advanced or metastatic triple-negative breast cancer previously treated with anthracyclines and taxanes. [2020]We conducted a multicenter phase I/II trial of olaparib plus eribulin in Japanese patients with advanced or metastatic triple-negative breast cancer (TNBC) to determine the recommended phase II dose (RP2D) (phase I) and to examine the efficacy and safety (phase II) (UMIN00009498) of the combined therapy.
A T-cell-engaging B7-H4/CD3-bispecific Fab-scFv Antibody Targets Human Breast Cancer. [2020]Label="PURPOSE">The B7 homolog 4 (B7-H4, VTCN1) is an immune checkpoint molecule that negatively regulates immune responses and is known to be overexpressed in many human cancers. Previously, we generated a mouse anti-human B7-H4 mAb that did not have a significant antitumor effect in vivo probably because of molecule instability. In this study, we designed a B7-H4/CD3-bispecific antibody (BsAb) and investigated its antitumor activity in vitro and in vivo using a humanized mouse model.
A phase I/II study of weekly nab-paclitaxel plus cisplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer. [2020]The aim of this study was to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC).
Novel sequential treatment with palbociclib enhances the effect of cisplatin in RB-proficient triple-negative breast cancer. [2022]Triple-negative breast cancer (TNBC) is a highly aggressive malignancy that lacks sensitivity to chemotherapy, endocrine therapy or targeted therapy. CDK4/6 inhibitors, combined with endocrine therapy, have been shown to be effective in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. Therefore, we investigated whether the CDK4/6 inhibitor palbociclib (PD) could enhance the effects of cisplatin (CDDP) on TNBC.
A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer. [2022]We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
Recent advances and challenges of bispecific antibodies in solid tumors. [2021]Cancer immunotherapy has made remarkable progress in the past decade. Bispecific antibodies (BsAbs) have acquired much attention as the next generation strategy of antibody-target cancer immunotherapy, which overwhelmingly focus on T cell recruitment and dual receptors blockade. So far, BsAb drugs have been proved clinically effective and approved for the treatment of hematologic malignancies, but no BsAb have been approved in solid tumors. Numerous designed BsAb drugs for solid tumors are now undergoing evaluation in clinical trials. In this review, we will introduce the formats of bispecific antibodies, and then update the latest preclinical studies and clinical trials in solid tumors of BsAbs targeting EpCAM, CEA, PMSA, ErbB family, and so on. Finally, we discuss the BsAb-related adverse effects and the alternative strategy for future study.
Association of Immune-Related Adverse Events, Hospitalization, and Therapy Resumption With Survival Among Patients With Metastatic Melanoma Receiving Single-Agent or Combination Immunotherapy. [2023]Immune-related adverse events (irAEs) due to immune checkpoint blockade (ICB) have been shown to be positively associated with survival. Among patients with metastatic melanoma, evidence supporting this association has been conflicting, while ipilimumab-nivolumab combination ICB has been examined only in small clinical cohorts.
Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B. [2023]Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3.
Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands. [2023]In phase III trials, ipilimumab plus nivolumab combination therapy is highly efficacious for advanced melanoma, despite many treatment-related grades 3-4 adverse events. Here, we report real-world safety and survival outcomes of ipilimumab plus nivolumab for advanced melanoma. Patients with advanced melanoma who received first-line ipilimumab plus nivolumab between January 1, 2015 and June 30, 2021 were selected from the Dutch Melanoma Treatment Registry. We evaluated response status at 3, 6, 12, 18, and 24 months. OS and PFS were estimated with the Kaplan-Meier method. Separate analyses were performed for patients with or without brain metastases and for patients who met the inclusion criteria of the Checkmate-067 trial. In total, 709 patients received first-line ipilimumab plus nivolumab. Three hundred sixty (50.7%) patients experienced grade 3-4 adverse events, with 211 of the (58.6%) patients requiring hospital admission. The median treatment duration was 42 days (IQR = 31-139). At 24 months, disease control was achieved in 37% of patients. Median PFS since the start of treatment was 6.6 months (95% CI: 5.3-8.7), and median OS was 28.7 months (95% CI: 20.7-42.2). CheckMate-067 trial-like patients had a 4-year OS of 50% (95% CI: 43-59). Among patients with no asymptomatic or symptomatic brain metastases, the 4-year OS probabilities were 48% (95% CI: 41-55), 45% (95% CI: 35-57), and 32% (95% CI: 23-46). Ipilimumab plus nivolumab can achieve long-term survival in advanced melanoma patients in a real-world setting, including patients not represented in the CheckMate-067 trial. However, the proportion of patients with disease control in the real world is lower compared with clinical trials.