ABBV-706 + Chemotherapy for Advanced Solid Cancers

Recruiting at 80 trial 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. ^{1 2 3 4 5}

What 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. ^{4 6 7 8 9}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility 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.

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.

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

Treatment Details

Interventions

• ABBV-706 (Monoclonal Antibodies)
• Budigalimab (Monoclonal Antibodies)
• Carboplatin (Chemotherapy)
• Cisplatin (Chemotherapy)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases. [2022]

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

The Dolaflexin-based Antibody-Drug Conjugate XMT-1536 Targets the Solid Tumor Lineage Antigen SLC34A2/NaPi2b. [2021]

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

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

5. United States 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Japan pubmed.ncbi.nlm.nih.gov

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

8. Japan 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. [2022]

9. United States 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. [2022]