AFM24 + Atezolizumab for Advanced Cancer

No longer recruiting at 20 trial locations

Overseen By Affimed GmbH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Affimed GmbH

Must not be taking: Anticancer, Investigational, Mitomycin, others

Disqualifiers: Active malignancy, Radiation, 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 tests a new combination of treatments: AFM24, an experimental treatment, and atezolizumab (Tecentriq), an immunotherapy drug. The aim is to determine if they can benefit people with advanced cancers that express the protein EGFR. The trial seeks to find the right dose and assess the treatment's effectiveness and safety for those whose cancer has progressed despite other treatments. It consists of two phases: one to determine the optimal dose and another to gather more information on its efficacy. Individuals with certain types of advanced or metastatic cancers, such as specific lung or gastric cancers, whose disease has continued to progress after standard treatments, may be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anticancer therapy, including investigational agents, at least 4 weeks before starting the study drug. If you are using certain drugs like mitomycin C or nitrosoureas, the period is 6 weeks, and for fluorouracil or small molecule targeted drugs, it's 2 weeks or 5 half-lives, whichever is longer.

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

Research has shown that the combination of AFM24 and atezolizumab is generally safe. One study found that taking 160 mg of AFM24 with atezolizumab was manageable in terms of safety, with side effects usually mild and controllable. Although all treatments can have side effects, current data suggest that this combination is generally well-tolerated. The treatment remains under study, so new safety information may emerge. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AFM24 combined with atezolizumab because this duo offers a new way to fight advanced cancer. Unlike traditional treatments that might target cancer cells directly, AFM24 uses a unique mechanism by engaging the immune system, specifically focusing on a protein called EGFR, which is often found on cancer cells. This approach could potentially enhance the immune response against tumors. When paired with atezolizumab, an immune checkpoint inhibitor, the combination might provide a powerful boost to the body's natural defenses, offering hope for more effective outcomes than current therapies.

What evidence suggests that AFM24 + Atezolizumab could be an effective treatment for advanced cancer?

Research has shown that using AFM24 with atezolizumab may help treat certain advanced cancers, particularly non-small cell lung cancer (NSCLC). Studies found that patients with a specific type of NSCLC, who did not respond to previous treatments, experienced better results with this combination. Higher doses of AFM24 led to improved overall response rates (ORR) and longer progression-free survival (PFS). The FDA has granted fast track status to this combination, indicating its potential to treat challenging cancer cases. The trial will include an Escalation Phase to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AFM24 with atezolizumab, followed by an Expansion Phase to gather preliminary evidence of efficacy and further confirm safety. This evidence suggests that AFM24 and atezolizumab together might be effective for patients with advanced cancers. ^{1 2 4 5 6}

Who Is on the Research Team?

Daniela Morales-Espinosa, MD

Principal Investigator

Affimed GmbH

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic EGFR-positive cancers, like NSCLC, gastric/GEJ adenocarcinoma, HCC, hepatobiliary-, or pancreatic cancer that's worsened after treatment. They must have had certain prior therapies and good organ function. People can't join if they've had recent radiation therapy, active malignancies (with some exceptions), recent anticancer treatments, are using traditional Chinese medicine for tumors, or are in another clinical study.

Inclusion Criteria

I have advanced liver, bile duct, or pancreatic cancer and have tried at least one standard treatment.

My organs are working well.

Phase 1: Evaluable or measurable disease per RECIST v1.1

Exclusion Criteria

I have no active cancers except for certain treated or non-threatening types.

I haven't had radiation therapy in the last 2 weeks or still have side effects from it.

I haven't taken any cancer drugs or traditional Chinese medicine for cancer in the last 2 to 6 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Participants receive a single dose of AFM24 and are observed for adverse events for 1 week

1 week

Dose Escalation

Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AFM24 in combination with atezolizumab using a 3+3 design

Estimated up to 36 weeks

Expansion

Collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab

Estimated up to 36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AFM24
• Atezolizumab

Trial Overview The AFM24-102 study tests the combination of a new drug called AFM24 with an existing cancer medication Atezolizumab in patients with specific advanced solid tumors expressing EGFR. It's an open-label Phase 1/2a trial where all participants receive the drugs to evaluate safety and effectiveness at different doses.

How Is the Trial Designed?

Group I: Expansion Phase Experimental Treatment 2 Interventions

The expansion phase will collect preliminary evidence of efficacy and further confirm the safety of AFM24 in combination with atezolizumab.

Group II: Escalation Phase Experimental Treatment 2 Interventions

The Escalation phase will determine the MTD/RP2D of AFM24 in combination with atezolizumab. A traditional 3+3 design will be used to determine the RP2D.

AFM24 is already approved in United States for the following indications:

Approved in United States as AFM24 for:

• Advanced and/or metastatic EGFR-expressing non-small cell lung cancer (NSCLC)

Who Is Running the Clinical Trial?

Affimed GmbH

Lead Sponsor

Trials

11

Recruited

650+

Published Research Related to This Trial

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

Atezolizumab combined with chemotherapy (ABCP or ACnP) has been shown to significantly improve progression-free survival (PFS) and overall survival (OS) in chemotherapy-naïve patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), based on the IMpower150 and IMpower130 studies.

Both treatment regimens (ABCP and ACnP) demonstrated manageable safety profiles, with most immune-related side effects being mild to moderate and reversible, making them promising first-line options for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab First-Line Combination Therapy: A Review in Metastatic Nonsquamous NSCLC. Dhillon, S., Syed, YY.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05109442

Study to Assess AFM24 in Combination With Atezolizumab ... The tumor types planned to be studied in the AFM24/atezolizumab combination study will be: Non-small cell lung cancer (EGFR-WT), with disease progression after ...

2. cancernetwork.com cancernetwork.com/view/afm24-atezolizumab-earns-fda-fast-track-status-in-egfr-wild-type-nsclc

AFM24/Atezolizumab Earns FDA Fast Track Status in ... Data from the phase 1/2a AFM24-102 trial support the fast track designation for the AFM24 combination in EGFR wild-type non–small cell lung ...

3. targetedonc.com targetedonc.com/view/higher-afm24-exposure-boosts-response-in-advanced-nsclc-aacr-data

Higher AFM24 Exposure Boosts Response in Advanced ... A post hoc analysis shows significantly improved ORR and PFS in advanced NSCLC with higher AFM24 exposure, supporting optimized dosing strategies.

4. onclive.com onclive.com/view/afm24-plus-atezolizumab-earns-fda-fast-track-designation-for-egfr-wild-type-nsclc

AFM24 Plus Atezolizumab Wins FDA Fast Track ... - OncLive AFM24 combined with atezolizumab shows promising efficacy in EGFR wild-type NSCLC patients resistant to prior therapies. The fast track ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05109442

Study to Assess AFM24 in Combination With Atezolizumab ... Affimed to Host Investor Conference Call Highlighting Clinical Data from AFM24 in Combination with Atezolizumab in Non-Small Cell Lung Cancer.

6. onclive.com onclive.com/view/afm24-plus-atezolizumab-shows-acceptable-safety-early-activity-in-egfr-solid-tumors

AFM24 Plus Atezolizumab Shows Acceptable Safety, Early ... “AFM24 [given] at 160 mg in combination with atezolizumab demonstrated a well-managed safety profile,” lead study author Omar Saavedra, MD, of ...