ABBV-706 + Chemotherapy for Advanced Solid Cancers

Not currently recruiting at 102 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must not be taking: Top1 inhibitors

Disqualifiers: Interstitial lung disease, Pneumonitis, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ABBV-706 (an anti-SEZ6 antibody-drug conjugate), for safety and effectiveness in treating certain advanced cancers. It focuses on small cell lung cancer (SCLC), high-grade brain tumors, and specific neuroendocrine cancers, which affect hormone-producing cells. Participants will receive either ABBV-706 alone or in combination with other drugs like budigalimab or chemotherapy. The trial includes individuals whose cancer has returned or did not respond to standard treatments, such as chemotherapy, and who have no other curative options. Participants must visit the hospital frequently for treatments and tests. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity 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 whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that ABBV-706 has been promising in early studies, with patients generally tolerating it well. Some studies found it effective for longer periods, and no major safety issues have been reported so far.

Safety information for the combination of ABBV-706 with budigalimab is still being collected. Researchers are carefully testing both treatments together to ensure their safety when used in combination.

When ABBV-706 is combined with well-known cancer treatments like carboplatin or cisplatin, the goal is to achieve both effectiveness and safety. Thorough testing will help confirm this.

As this trial is in its early phase, the main focus is on identifying the safest dose. Researchers are closely monitoring for any side effects. Participants will be monitored carefully to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

ABBV-706 is unique because it targets specific markers on cancer cells, potentially offering a more precise attack on tumors compared to the broader approach of traditional chemotherapies like carboplatin and cisplatin. Researchers are excited about ABBV-706 as it could minimize damage to healthy cells and reduce side effects, a significant improvement over existing treatments for advanced solid cancers. Additionally, combining ABBV-706 with budigalimab, an immune-modulating drug, might enhance the body's ability to fight cancer, providing a novel dual approach to treatment.

What evidence suggests that this trial's treatments could be effective for advanced solid cancers?

Research has shown that ABBV-706, a targeted cancer treatment, yields promising results for certain cancers. It targets a protein called SEZ6 and delivers a potent drug directly to cancer cells, inhibiting their growth. In this trial, some participants with small cell lung cancer (SCLC) will receive ABBV-706 monotherapy, which has demonstrated responses similar to standard treatments. Other participants will receive ABBV-706 combined with chemotherapy drugs like carboplatin or cisplatin, which has shown progress in treating advanced solid tumors. Additionally, the trial is studying the combination of ABBV-706 with another investigational drug, budigalimab, for its potential to improve outcomes in neuroendocrine carcinomas, a type of cancer that originates in hormone-producing cells. ^{3 4 5 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-706
• Budigalimab
• Carboplatin
• Cisplatin

Trial Overview 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.

How Is the Trial Designed?

Group I: Part 4b: ABBV-706 Monotherapy Dose Expansion NECs Experimental Treatment 1 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 Tumors Experimental Treatment 1 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 Chemotherapy Experimental Treatment 3 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 + Budigalimab Experimental Treatment 2 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 Expansion Experimental Treatment 1 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 Escalation Experimental Treatment 1 Intervention

Participants will receive escalating doses of ABBV-706 until doses for optimization are determined, as part of an approximately 1 year treatment period.

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

The standard treatment for platinum-resistant ovarian cancer involves non-platinum chemotherapy, with weekly paclitaxel showing the greatest benefits, but overall response rates remain modest, highlighting the need for improved therapies.

Recent trials indicate that while combination treatments with antiangiogenics have improved outcomes, there is still a lack of reliable biomarkers to predict treatment response, emphasizing the importance of thoughtful clinical trial designs and the exploration of novel therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. Eskander, RN., Moore, KN., Monk, BJ., et al.[2023]

XMT-1536 is a novel antibody-drug conjugate targeting NaPi2b, showing promising preclinical antitumor effects in ovarian and lung adenocarcinoma models, with low systemic exposure to the active drug, suggesting a favorable safety profile.

Despite NaPi2b being expressed in both tumors and normal tissues, XMT-1536 demonstrated controlled bystander killing, which may enhance its therapeutic efficacy while minimizing on-target toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Dolaflexin-based Antibody-Drug Conjugate XMT-1536 Targets the Solid Tumor Lineage Antigen SLC34A2/NaPi2b. Bodyak, ND., Mosher, R., Yurkovetskiy, AV., et al.[2021]

Recent studies of over 500 cisplatin analogs have shown that the choice of carrier ligands significantly influences the antitumor activity and spectrum of these platinum complexes, while the leaving groups affect their solubility and toxicity.

Clinical trials in Japan have indicated that some new platinum complexes exhibit less nephrotoxicity compared to cisplatin, although they may cause myelotoxicity, suggesting a need for further research to optimize their safety and efficacy profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The prospect for cisplatin analogs from the experimental standpoint]. Tashiro, T.[2013]

The study highlights that combining Cisplatin derivatives with various anticancer agents and immunotherapeutics can enhance their effectiveness while reducing toxicity, addressing the common issues of resistance and side effects in cancer treatment.

Utilizing targeted nanocarriers for drug delivery improves the accumulation of these therapies in tumor tissues, leading to better therapeutic outcomes and minimizing the adverse effects associated with traditional platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases. Tsvetkova, D., Ivanova, S.[2022]

In a phase II study involving 37 patients with advanced squamous cell lung cancer (SQCLC), the combination of gemcitabine and albumin-bound paclitaxel (ABP) achieved a high overall response rate (ORR) of 59%, indicating significant antitumor efficacy.

The treatment was found to be safe and well-tolerated, with a median progression-free survival (PFS) of 7.5 months, outperforming traditional carboplatin doublet regimens and showing comparable efficacy to more complex combinations like carboplatin plus taxane plus pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Albumin-Bound Paclitaxel and Gemcitabine in Patients with Newly Diagnosed Stage IV Squamous Cell Lung Cancers. Paik, PK., Kim, RK., Ahn, L., et al.[2022]

In a phase II study involving 71 chemotherapy-naïve patients with squamous cell carcinoma of the lung, the overall response rate for carboplatin plus weekly albumin-bound paclitaxel (CnP) was 47%, which is comparable to 43% for cisplatin plus gemcitabine (CG).

While both treatment regimens showed similar efficacy, they differed in toxicity profiles: the CG arm experienced more hematologic toxicities, while the CnP arm had higher rates of anemia and sensory neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of carboplatin + nab-paclitaxel versus cisplatin + gemcitabine for chemotherapy-naïve squamous cell carcinoma: North Japan lung cancer study group 1302. Kawashima, Y., Harada, T., Fujita, Y., et al.[2022]

Cisplatin and carboplatin are key chemotherapy drugs for various cancers, and new 'third-generation' platinum-based agents like oxaliplatin and ZD0473 are being tested to expand their effectiveness.

Research is also focused on improving the safety of platinum drugs through combination therapies with other anticancer agents and developing new formulations like liposomal and polymeric platinum complexes to reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meeting report on 8th International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy. Kelland, LR.[2018]

Platinum-containing drugs like cisplatin, carboplatin, and oxaliplatin have been effective in treating cancers such as testicular, ovarian, and colorectal cancer, but there is potential for expanding their use through new drug analogues and combinations with targeted therapies.

Recent developments include promising clinical activity of new analogues like satraplatin for hormone-refractory prostate cancer and picoplatin for small-cell lung cancer, as well as innovative delivery methods for platinum drugs that are currently in early clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broadening the clinical use of platinum drug-based chemotherapy with new analogues. Satraplatin and picoplatin. Kelland, L.[2019]

B7-H4 is overexpressed in 92% of high-grade serous ovarian carcinoma (HGSOC) tumors, including recurrent cases after platinum treatment, making it a promising target for therapy.

The B7-H4-directed antibody-drug conjugate (B7-H4-ADC) demonstrated significant efficacy in platinum- and PARP inhibitor-resistant HGSOC models, leading to tumor regression in 65.5% of patient-derived xenograft (PDX) models and increased survival with scheduled dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A B7-H4 targeting antibody-drug conjugate shows anti-tumor activity in PARPi and platinum resistant cancers with B7-H4 expression. Gitto, SB., Whicker, M., Davies, G., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05599984

NCT05599984 | Study to Evaluate Adverse Events, ... The purpose of this study is to assess safety, tolerability, pharmacokinetics and preliminary efficacy of ABBV-706 as a monotherapy and in combination with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3001

First-in-human study of ABBV-706, a seizure-related ... ABBV-706 is an ADC targeting SEZ6 conjugated to a topoisomerase 1 inhibitor payload at a drug-to-antibody ratio of 6, and is highly efficacious in preclinical ...

3. news.abbvie.com news.abbvie.com/2025-05-27-AbbVie-Features-New-Data-Across-Difficult-to-Treat-Solid-Tumors-and-Blood-Cancers-at-ASCO-2025,-Highlighting-Breadth-and-Depth-of-its-Oncology-Portfolio

AbbVie Features New Data Across Difficult-to-Treat Solid ... These new data highlight significant progress in AbbVie's robust oncology pipeline, across a range of difficult-to-treat solid tumors and blood cancers.

4. onclive.com onclive.com/view/abbv-706-yields-durable-responses-and-is-deemed-tolerable-in-r-r-sclc

ABBV-706 Yields Durable Responses and Is Deemed ... The SEZ6-targeting ADC ABBV-706 generated durable efficacy outcomes comparable with those of first-line SOC in patients with ...

5. withpower.com withpower.com/trial/phase-1-neoplasms-10-2022-569f7

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, ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.105

Safety and efficacy of ABBV-706, a seizure-related ... ABBV-706, a unique antibody-drug conjugate comprising a SEZ6-directed antibody conjugated to a potent topoisomerase 1 inhibitor payload, is ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03692-X/fulltext

2029TiP Phase I study of ABBV-706, an anti-SEZ6 ... The study will evaluate the preliminary safety, tolerability, pharmacokinetics (PK), and antitumor activity of ABBV-706 as monotherapy and in combination with ...