ABBV-706 + Chemotherapy for Advanced Solid Cancers
Recruiting in Palo Alto (17 mi)
+79 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: AbbVie
Must not be taking: Top1 inhibitors
Disqualifiers: Interstitial lung disease, Pneumonitis, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests a new drug, ABBV-706, alone or with other drugs to treat aggressive cancers like small cell lung cancer and certain brain tumors. It aims to find the best dose and check its safety and effectiveness. The study involves periodic hospital visits and medical tests over several years.
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 coordinators or your doctor.
What data supports the effectiveness of the drug ABBV-706 + Chemotherapy for Advanced Solid Cancers?
The research highlights that antibody-drug conjugates (ADCs), like ABBV-706, have shown effectiveness in treating some solid and blood cancers. Additionally, combining platinum-based drugs like cisplatin and carboplatin with other cancer treatments can enhance their effectiveness and reduce resistance.
12345What makes the drug ABBV-706 + Chemotherapy unique for treating advanced solid cancers?
The drug ABBV-706 combined with chemotherapy is unique because it includes an anti-SEZ6 antibody-drug conjugate, which targets specific proteins on cancer cells, potentially enhancing the effectiveness of traditional chemotherapy agents like carboplatin and cisplatin.
46789Eligibility Criteria
Adults with advanced solid tumors, including specific types of lung cancer and high-grade brain or neuroendocrine cancers that have worsened despite standard treatments. Participants must be in good physical condition (ECOG 0-1), have acceptable heart function, and measurable disease. Those with certain lung conditions or previous treatment with similar drugs are excluded.Inclusion Criteria
Laboratory values criteria met within 7 days prior to the first dose of study drug as per the protocol
My small cell lung cancer has worsened after initial platinum-based treatment.
My brain tumor has grown or returned, confirmed by MRI or biopsy, after recent radiation therapy.
+10 more
Exclusion Criteria
I have previously been treated with a SEZ6-targeted antibody drug.
I have never needed steroids for lung inflammation.
I have been treated with a specific type of targeted therapy before.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
ABBV-706 is intravenously infused in escalating doses as a monotherapy until the maximum tolerated dose is determined
Approximately 1 year
Regular visits for dose escalation monitoring
Dose Optimization and Expansion
Participants receive varying doses of ABBV-706 in a randomized manner to determine the recommended Phase 2 dose
Approximately 1 year
Regular visits for dose optimization and monitoring
Combination Treatment
Participants receive ABBV-706 in combination with budigalimab, carboplatin, or cisplatin
Approximately 1 year
Every 3 weeks for combination treatment
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 2 years
Participant Groups
The trial is testing ABBV-706 alone or combined with budigalimab, carboplatin, or cisplatin for treating various advanced cancers. It involves escalating doses to find the maximum tolerated dose and then further study at selected doses to assess safety and preliminary effectiveness.
6Treatment groups
Experimental Treatment
Group I: Part 4b: ABBV-706 Monotherapy Dose Expansion NECsExperimental Treatment1 Intervention
Participants with R/R neuroendocrine carcinomas (NECs) will receive IV Infused ABBV-706 as a monotherapy at or below the MTD/MAD, as part of an approximately 1 year treatment period.
Group II: Part 4a: ABBV-706 Monotherapy Dose Expansion CNS TumorsExperimental Treatment1 Intervention
Participants with relapsed/refractory (R/R) central nervous system (CNS) tumors will receive ABBV-706 as a monotherapy at or below the maximum tolerated dose (MTD) maximum administered dose (MAD), as part of an approximately 1 year treatment period.
Group III: Part 3b: ABBV-706 + Platinum ChemotherapyExperimental Treatment3 Interventions
Participants will receive ABBV-706 in combination with carboplatin or cisplatin, as part of an approximately 1 year treatment period.
Group IV: Part 3a: ABBV-706 + BudigalimabExperimental Treatment2 Interventions
Participants will receive ABBV-706 in combination with budigalimab, as part of an approximately 1 year treatment period.
Group V: Part 2: ABBV-706 Monotherapy Dose Optimization and ExpansionExperimental Treatment1 Intervention
Participants with small cell lung cancer will receive varying doses of ABBV-706 in a randomized manner until the recommended phase 2 dose (RP2D) is achieved, as part of an approximately 1 year treatment period..
Group VI: Part 1: ABBV-706 Monotherapy Dose EscalationExperimental Treatment1 Intervention
Participants will receive escalating doses of ABBV-706 until doses for optimization are determined, as part of an approximately 1 year treatment period.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Banner MD Anderson Cancer Ctr /ID# 260129Gilbert, AZ
City Of Hope Comprehensive Cancer Center /ID# 271295Duarte, CA
City of Hope Orange County Lennar Foundation Cancer Center /ID# 259884Irvine, CA
Yale New Haven Hospital /ID# 246647New Haven, CT
More Trial Locations
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Who Is Running the Clinical Trial?
AbbVieLead Sponsor
References
Overcoming the challenges of drug development in platinum-resistant ovarian cancer. [2023]The definition of "platinum-resistant ovarian cancer" has evolved; it now also reflects cancers for which platinum treatment is no longer an option. Standard of care for platinum-resistant ovarian cancer is single-agent, non-platinum chemotherapy with or without bevacizumab, which produces modest response rates, with the greatest benefits achieved using weekly paclitaxel. Several recent phase 3 trials of pretreated patients with prior bevacizumab exposure failed to meet their primary efficacy endpoints, highlighting the challenge in improving clinical outcomes among these patients. Combination treatment with antiangiogenics has improved outcomes, whereas combination strategies with immune checkpoint inhibitors have yielded modest results. Despite extensive translational research, there has been a lack of reliable and established biomarkers that predict treatment response in platinum-resistant ovarian cancer. Additionally, in the platinum-resistant setting, implications for the time between the penultimate dose of platinum therapy and platinum retreatment remain an area of debate. Addressing the unmet need for an effective treatment in the platinum-resistant setting requires thoughtful clinical trial design based on a growing understanding of the disease. Recent cancer drug approvals highlight the value of incorporating molecular phenotypes to better define patients who are more likely to respond to novel therapies. Clinical trials designed per the Gynecologic Cancer InterGroup recommendations-which advocate against relying solely upon the platinum-free interval-will help advance our understanding of recurrent ovarian cancer response where platinum rechallenge in the platinum-resistant setting may be considered. The inclusion of biomarkers in clinical trials will improve patient stratification and potentially demonstrate correlations with biomarker expression and duration of response. With the efficacy of antibody-drug conjugates shown for the treatment of some solid and hematologic cancers, current trials are evaluating the use of various novel conjugates in the setting of platinum-resistant ovarian cancer. Emerging novel treatments coupled with combination trials and biomarker explorations offer encouraging results for potential strategies to improve response rates and prolong progression-free survival in this population with high unmet need. This review outlines existing data from contemporary clinical trials of patients with platinum-resistant ovarian cancer and suggests historical synthetic benchmarks for non-randomized trials.
Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases. [2022]The problems with anticancer therapy are resistance and toxicity. From 3000 Cisplatin derivatives tested as antitumor agents, most of them have been rejected, due to toxicity. The aim of current study is the comparison of therapeutic combinations of the currently applied in clinical practice: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin. The literature data show that the strategies for the development of platinum anticancer agents and bypassing of resistance to Cisplatin derivatives and their toxicity are: combination therapy, Pt IV prodrugs, the targeted nanocarriers. The very important strategy for the improvement of the antitumor effect against different cancers is synergistic combination of Cisplatin derivatives with: (1) anticancer agents-Fluorouracil, Gemcitabine, Cytarabine, Fludarabine, Pemetrexed, Ifosfamide, Irinotecan, Topotecan, Etoposide, Amrubicin, Doxorubicin, Epirubicin, Vinorelbine, Docetaxel, Paclitaxel, Nab-Paclitaxel; (2) modulators of resistant mechanisms; (3) signaling protein inhibitors-Erlotinib; Bortezomib; Everolimus; (4) and immunotherapeutic drugs-Atezolizumab, Avelumab, Bevacizumab, Cemiplimab, Cetuximab, Durvalumab, Erlotinib, Imatinib, Necitumumab, Nimotuzumab, Nivolumab, Onartuzumab, Panitumumab, Pembrolizumab, Rilotumumab, Trastuzumab, Tremelimumab, and Sintilimab. An important approach for overcoming the drug resistance and reduction of toxicity of Cisplatin derivatives is the application of nanocarriers (polymers and liposomes), which provide improved targeted delivery, increased intracellular penetration, selective accumulation in tumor tissue, and enhanced therapeutic efficacy. The advantages of combination therapy are maximum removal of tumor cells in different phases; prevention of resistance; inhibition of the adaptation of tumor cells and their mutations; and reduction of toxicity.
The Dolaflexin-based Antibody-Drug Conjugate XMT-1536 Targets the Solid Tumor Lineage Antigen SLC34A2/NaPi2b. [2021]Target selection for antibody-drug conjugates (ADC) frequently focuses on identifying antigens with differential expression in tumor and normal tissue, to mitigate the risk of on-target toxicity. However, this strategy restricts the possible target space. SLC34A2/NaPi2b is a sodium phosphate transporter expressed in a variety of human tumors including lung and ovarian carcinoma, as well as the normal tissues from which these tumors arise. Previous clinical trials with a NaPi2b targeting MMAE-ADCs have shown objective durable responses. However, the protein-based biomarker assay developed for use in that study was unable to discern a statistically significant relationship between NaPi2b protein expression and the probability of response. XMT-1536 is a NaPi2b targeting ADC comprised of a unique humanized antibody conjugated with 10-15 auristatin F- hydroxypropylamide (AF-HPA) payload molecules via the Dolaflexin platform. AF-HPA is a cell-permeable, antimitotic compound that is slowly metabolized intratumorally to an active, very low-permeable metabolite, auristatin F (AF), resulting in controlled bystander killing. We describe the preclinical in vitro and in vivo antitumor effects of XMT-1536 in models of ovarian and lung adenocarcinoma. Pharmacokinetic analysis showed approximately proportional increases in exposure in rat and monkey. Systemic free AF-HPA and AF concentrations were observed to be low in all animal species. Finally, we describe a unique IHC reagent, generated from a chimeric construct of the therapeutic antibody, that was used to derive a target expression and efficacy relationship in a series of ovarian primary xenograft cancer models.
Meeting report on 8th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy. [2018]The platinum-based drugs, cisplatin and carboplatin, represent major agents in the chemotherapeutic treatment of a variety of types of cancer. Novel, "third-generation" agents aimed at broadening the clinical activity of this class of drug are currently undergoing clinical evaluation. These include oxaliplatin, ZD0473 and BBR3464. Clinical trials and preclinical studies are also being conducted with liposomal (SPI-077 and L-NDDP) and polymeric platinum complexes (linked to HPMA or albumin). Combination studies of cisplatin/carboplatin with other anticancer drugs such as gemcitabine and UCN-01 (7-hydroxystaurosporine) and agents designed to reduce platinum drug toxicities (e.g., BNP-7787, DIMESNA) are ongoing. Preclinically, there is interest in trans platinum complexes, terpyridine platinum(II) complexes and other metal-containing agents (ruthenium and gold).
A B7-H4 targeting antibody-drug conjugate shows anti-tumor activity in PARPi and platinum resistant cancers with B7-H4 expression. [2023]Platinum and PARP inhibitors (PARPi) demonstrate activity in breast and ovarian cancers, but drug resistance ultimately emerges. Here we examine B7-H4 expression in primary and recurrent high-grade serous ovarian carcinoma (HGSOC) and the activity of a B7-H4-directed antibody-drug conjugate (B7-H4-ADC), using a pyrrolobenzodiazepine-dimer payload, in PARPi- and platinum-resistant HGSOC patient derived xenograft (PDX) models.
Broadening the clinical use of platinum drug-based chemotherapy with new analogues. Satraplatin and picoplatin. [2019]The three platinum-containing drugs that have been thus far approved by the FDA - cisplatin, carboplatin and oxaliplatin - have had a significant effect in the treatment of patients with some malignancies such as testicular, ovarian and colorectal cancer. However, much more remains to be achieved to widen the therapeutic use of this important class of drug, either via further analogue development or by judicious use of combining the existing drugs with new molecularly targeted agents. Two analogues arising from an academic (Institute of Cancer Research)/pharmaceutical (Johnson Matthey/AnorMed) collaboration - satraplatin (JM-216) and picoplatin (JM-/AMD-473) - have recently shown promising clinical activity; satraplatin (an orally available drug) in hormone-refractory prostate cancer and picoplatin in small-cell lung cancer. There have also been advances in delivery vehicles for platinum drugs (e.g., the diaminocyclohexane [DACH]-based AP-5346 and aroplatin/liposomal cis-bis-neodecanoato-trans-(R,R)-1,2-diaminocyclohexane platinum (II) [L-NDDP] are in early clinical development). Platinum-based drugs have also been successfully combined with molecularly targeted drugs (e.g., the recent approval of the vascular endothelial growth factor monoclonal antibody bevacizumab with carboplatin and paclitaxel in patients with NSCLC).
[The prospect for cisplatin analogs from the experimental standpoint]. [2013]In the last decade a number of cisplatin analogs have been extensively synthesized to develop new Pt complexes with better antitumor activity and less nephrotoxicity than cisplatin. Antitumor Pt complexes consist of two carrier ligands and two or four leaving groups according to Pt valence. Our screening results of over 500 Pt complexes suggested that the carrier ligands influenced antitumor activity, especially the antitumor spectrum, while the leaving groups affected water solubility, stability, toxicity, and so forth. Recently, more than 10 cisplatin analogs have been clinically tested. In Japan four complexes have been evaluated in phase II. Most of them showed less nephrotoxicity than cisplatin. Instead, myelotoxicity was often observed. These complexes were significantly effective against various murine Their antitumor spectra, however, were somewhat different from each other. The Pt complexes such as cisplatin, carboplatin and 254-S, having the same carrier ligands, diammine, showed a quite similar spectrum. Sensitivity of cell lines derived from human tumors to these analogs were also examined in vivo and/or in vitro. So far as reported, their antitumor spectra were not so different from that of cisplatin. The cross-resistance patterns of cisplatin-resistant sublines to the complexes also depend on types of carrier ligands. Besides, L-1210/DDP showed cross-resistance only to a few carrier ligands, whereas P388/DDP did so to all of them tested. Thus, it might be a reasonable trial to search for a carrier ligand, the complexes of which would show a unique and broad antitumor spectrum including cisplatin-resistant lines and, in addition, not only against murine tumors but against human tumor cells.
Randomized phase II trial of carboplatin + nab-paclitaxel versus cisplatin + gemcitabine for chemotherapy-naïve squamous cell carcinoma: North Japan lung cancer study group 1302. [2022]A subset analysis of the CA031 trial showed significant improvement in the overall response rate after administration of carboplatin plus weekly albumin-bound paclitaxel compared to carboplatin plus paclitaxel for squamous cell carcinoma of the lung (SQ). We conducted this phase II study to compare carboplatin plus weekly albumin-bound paclitaxel (CnP) to cisplatin plus gemcitabine (CG), a standard regimen for SQ.
A Phase II Trial of Albumin-Bound Paclitaxel and Gemcitabine in Patients with Newly Diagnosed Stage IV Squamous Cell Lung Cancers. [2022]Gemcitabine and albumin-bound paclitaxel (ABP) exhibit synergistic antitumor efficacy, with ABP serving to increase the intratumoral gemcitabine concentration. Both drugs are active in squamous cell lung cancers (SQCLC) and are conventional partners for carboplatin. We hypothesized that combining gemcitabine and ABP would enhance the antitumor activity in patients with advanced SQCLCs.