Immunotherapy with ABBV-927 + ABBV-181 for Cancer

Not currently recruiting at 27 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune disease, Immunodeficiency, Uncontrolled hypertension, 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 aims to test the safety and optimal dose of two new treatments, ABBV-927 and ABBV-181 (both experimental immunotherapy drugs), for individuals with advanced solid tumors, such as head and neck cancer or lung cancer. Researchers seek to determine how these treatments work both individually and in combination. Participants may qualify if they have advanced cancer that has spread or returned after standard treatments, such as chemotherapy or immunotherapy. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive these new therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have used immunosuppressive medication within 14 days before starting the trial. It's best to discuss your specific medications with the trial team.

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

In a previous study, researchers tested ABBV-927 alone and with another treatment called ABBV-181. The main goal was to assess the safety of these treatments. ABBV-927 has been administered to patients with solid tumors to determine the optimal dose. While some side effects occurred, most were mild or manageable, indicating the treatment was generally well-tolerated.

For the combination of ABBV-927 and ABBV-181, other studies have also examined safety. Again, the treatments were mostly well-tolerated, with some patients experiencing side effects that were usually not severe.

As this trial is in the first phase, researchers are still determining the safest way to administer these treatments. They closely monitor patient reactions to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments ABBV-927 and ABBV-181 because they bring new approaches to fighting cancer. Unlike traditional chemotherapy, which attacks both cancerous and healthy cells, these treatments focus on boosting the body's immune system to specifically target and destroy cancer cells. ABBV-927 is an immunotherapy that acts as an immune activator, while ABBV-181 is an antibody designed to enhance the immune response against tumors. This combination aims to provide a more targeted attack on cancers such as Non-Small Cell Lung Cancer (NSCLC) and Head and Neck Squamous Cell Carcinoma (HNSCC), potentially offering improved effectiveness and fewer side effects compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that ABBV-927 and ABBV-181 are under testing for their potential to treat advanced solid tumors. In this trial, some participants will receive ABBV-927 alone, designed to help the immune system find and destroy cancer cells. Others will receive a combination of ABBV-927 and ABBV-181, which aids the immune system in recognizing and attacking cancer cells. Although more data is needed, initial results have shown promise for treating certain cancers, such as those of the head, neck, and lungs. These treatments aim to enhance the body's natural defenses to fight cancer more effectively. ^{1 2 3 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors who have tried standard treatments without success or can't tolerate them. They must have good liver, kidney, and bone marrow function, stable heart health, and a performance status indicating they are fully active or restricted in physically strenuous activity but ambulatory. Not eligible if using immunosuppressants (with exceptions), history of severe immune-related neurotoxicity/pneumonitis from immunotherapy, uncontrolled diseases like hypertension or arrhythmia, pregnant/breastfeeding/planning to conceive soon.

Inclusion Criteria

My liver function tests are within the required range.

My cancer has worsened despite treatment, or I cannot tolerate the treatment.

I can carry out all my usual activities without help.

Exclusion Criteria

Participant must not have a history of coagulopathy or a platelet disorder associated with significant clinical risk of thromboembolic event in the judgement of the investigator, or major thromboembolic event within 6 months prior to the first dose of study treatment

I haven't taken immunosuppressive drugs in the last 14 days, with some exceptions.

I have never had severe nerve or lung problems from immunotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Treatment

Participants receive escalating doses of ABBV-927 and ABBV-181 to determine the maximum tolerated dose or recommended Phase 2 dose

8 weeks

Dose-Expansion Treatment

Additional participants receive the determined dose of ABBV-927 and ABBV-181 to further evaluate safety and efficacy

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABBV-181
• ABBV-927

Trial Overview The study tests ABBV-927 and ABBV-181 as potential cancer treatments. It's a dose-escalation study to find the safest and most effective doses when given alone or together. Participants will be monitored for how their bodies absorb these drugs (pharmacokinetics) and respond to them (pharmacodynamics).

How Is the Trial Designed?

Group I: Expansion Arm C: ABBV-927+ABBV-181 Experimental Treatment 2 Interventions

Additional participants with NSCLC will receive IV doses of ABBV-927 and IV doses of ABBV-181.

Group II: Expansion Arm B: ABBV-927+ABBV-181 Experimental Treatment 2 Interventions

Additional participants with HNSCC will receive IT doses of ABBV-927 and IV doses of ABBV-181.

Group III: Expansion Arm A: ABBV-927 Experimental Treatment 1 Intervention

Additional participants with HNSCC or NSCLC will receive intravenous (IV) doses of ABBV-927.

Group IV: Escalating Arm 6 (Japan): ABBV-927+ABBV-181 Experimental Treatment 2 Interventions

Participants with solid tumors will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181.

Group V: Escalating Arm 5 (Japan): ABBV-927 Experimental Treatment 1 Intervention

Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927.

Group VI: Escalating Arm 4: ABBV-927+ABBV-181 Experimental Treatment 2 Interventions

Participants with Head and Neck Squamous Cell Carcinoma (HNSCC) will receive escalating IT doses of ABBV-927 and IV doses of ABBV-181.

Group VII: Escalating Arm 3: ABBV-927+ABBV-181 Experimental Treatment 2 Interventions

Participants with Non-Small Cell Lung Cancer (NSCLC) will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181.

Group VIII: Escalating Arm 2: ABBV-927 Experimental Treatment 1 Intervention

Participants with solid tumors will receive escalating intratumoral (IT) doses of ABBV-927.

Group IX: Escalating Arm 1: ABBV-927 Experimental Treatment 1 Intervention

Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927.

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 novel PD-1 B-cell peptide vaccine (PD1-Vaxx) demonstrated superior efficacy compared to standard anti-PD-1 monoclonal antibodies in preclinical mouse models of colon carcinoma, suggesting it may be a promising alternative for cancer treatment.

Combining PD1-Vaxx with a HER-2 peptide vaccine resulted in enhanced tumor growth inhibition, and both vaccines showed a favorable safety profile with no observed toxicity or autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. Kaumaya, PTP., Guo, L., Overholser, J., et al.[2021]

Immunotherapy targeting PD-1/PD-L1 and CTLA-4 has shown increased survival benefits in treating metastatic non-small cell lung cancer (NSCLC), but it is also associated with significant cardiotoxicity, particularly high-grade conduction disorders like 3rd degree heart block.

A case study highlighted a patient who developed 3rd degree heart block 16 days after starting combination therapy with ipilimumab and nivolumab, emphasizing that over 75% of immunotherapy-related cardiotoxicity cases occur within the first 6 weeks, which underscores the need for early identification and monitoring of high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy-associated complete heart block in a patient with NSCLC: A case report and literature review. Vartanov, A., Kalotra, A., Varughese, J., et al.[2021]

In a study of 111 melanoma patients treated with immunotherapy or targeted therapy, the majority received immunotherapy, particularly anti-PD-1 treatments, with a total of 371 adverse events (AEs) reported.

The incidence of AEs was lower in patients receiving anti-PD-1 therapy, with only 15.3% experiencing severe (grade 3 to 4) AEs, which were more common in those on targeted therapies, highlighting the need for better reporting and understanding of both known and unknown AEs in cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. Aguiar, JP., Cardoso Borges, F., Murteira, R., et al.[2021]

Anti-CTLA4 and anti-PD1/PD-L1 immunotherapies represent a significant shift in cancer treatment by enhancing the immune system's ability to fight tumors rather than directly targeting the tumor cells themselves.

These immunotherapies can lead to unique immune-related adverse events due to the activation of the immune system against normal tissues, necessitating changes in clinical management to address potential autoimmune reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Champiat, S., Michot, JM., Lambotte, O.[2019]

The combination of GVAX and 3.0 mg/kg ipilimumab is safe and tolerable for patients with metastatic castration-resistant prostate cancer (mCRPC), with manageable immune-related adverse events observed during the study.

Out of 28 patients, 25% experienced a significant decline in prostate-specific antigen levels, indicating potential efficacy of the treatment, particularly at the 3.0 mg/kg dose level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. van den Eertwegh, AJ., Versluis, J., van den Berg, HP., et al.[2021]

A large-scale retrospective study of 2094 cases from the FDA adverse event reporting system found that combining immune checkpoint inhibitors with bevacizumab significantly increases the risk of adverse drug reactions (ADRs) in cancer patients, particularly interstitial lung disease, hypertension, and gastrointestinal bleeding.

The study highlights that combination therapy is an independent risk factor for these ADRs, suggesting the need for careful monitoring and individualized management strategies for patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. Gu, T., Jiang, A., Zhou, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03893955

NCT03893955 | A Study to Determine the Safety, ... A study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-927 with ABBV-368, Budigalimab (ABBV-181) and/or ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02988960

NCT02988960 | A Study of ABBV-927 and ABBV-181, an ... This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of ABBV-927, and to determine the maximum tolerated ...

3. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M19-037

M19-037 A study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-927 with ABBV-368, Budigalimab (ABBV-181) and/or ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11506581/

Review of Current and Future Medical Treatments in Head ... Cetuximab plus radiation resulted in an overall survival of 49 months compared with 29.3 months with RT alone (HR 0.73) in a pivotal trial ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7694874/

Checkpoint immunotherapy in head and neck cancers - PMC In the initial cohort of 60 patients, pembrolizumab was well tolerated with 17% of patients having a grade 3 or 4 drug-related adverse event [79]. The overall ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02988960/

Clinical Trial: NCT02988960 This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of ABBV-927, and to determine the ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS3147

A phase I study of CD40 agonist ABBV-927 plus OX40 ... The recommended Phase 2 dose (RP2D) will first be identified with ABBV-927 + ABBV-368 in patients with solid tumors (Arm A) and will be expanded ...