Immunotherapy with ABBV-927 + ABBV-181 for Cancer

Recruiting at 22 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

163 Participants Needed

Trial Summary

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.

What safety information is available for immunotherapy treatments like ABBV-927 and ABBV-181?

Immunotherapy treatments, including those targeting PD-1/PD-L1 and CTLA-4, can have side effects such as heart issues and autoimmune reactions, where the immune system attacks normal tissues. These side effects can vary in severity, and some may occur soon after starting treatment. ^{1 2 3 4 5}

How does the drug ABBV-927 + ABBV-181 differ from other cancer treatments?

The combination of ABBV-927 and ABBV-181 is unique because it involves immunotherapy, which uses the body's immune system to fight cancer, potentially offering a novel mechanism of action compared to traditional chemotherapy or radiation. This approach may provide a new option for patients, especially if standard treatments are not effective. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of ABBV-927, and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 in participants with advanced solid tumors.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Immunotherapy-associated complete heart block in a patient with NSCLC: A case report and literature review. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Safety of two-dose COVID-19 vaccination (BNT162b2 and CoronaVac) in adults with cancer: a territory-wide cohort study. [2023]

4. France pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. [2019]

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

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. [2023]

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

Development of PROSTVAC immunotherapy in prostate cancer. [2021]

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

Newcastle disease virus-infected intact autologous tumor cell vaccine for adjuvant active specific immunotherapy of resected colorectal carcinoma. [2004]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect. [2021]

9. England 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. [2021]

10. United States 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. [2021]