Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

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.

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

AFM24

Atezolizumab 840 MG in 14 ML Injection

Affimed GmbH

Anthony El-Khoueiry, MD

Marina Garassino, MD

Eric Christenson, MD

Danielle Wendler

Jin Won Kim

Yu Jung Kim

Hye Ryun Kim

Byoung Yong Shim

Slawomir Mandziuk, MD

Caezary Szczylik, MD

Rodryg Ramlau, MD

Wojciech Rogowski, MD

Iwona Lugowska, MD

Omar Saavedra, MD

Valentina Boni

Mariano Ponz-Sarvise

Andrés Cervantes, MD

Juanita Lopez, MD

Daniela Morales-Espinosa, MD

AFM24-102 is a Phase 1/2a open-label, non-randomized, multicenter, dose escalation, and expansion study evaluating AFM24 in combination with atezolizumab in patients with selected EGRF-expressing advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies.

There will be 2 parts in this study: a dose escalation phase (phase 1) and an expansion phase (phase 2a). Patients will qualify to receive the investigational drugs (AFM24 + atezolizumab) in the dose escalation phase or the expansion phase only if they are deemed eligible following the safety lead-in phase. Seven days before the planned first combination treatment, patients will receive a single dose of AFM24 and will be observed for any adverse events for 1 week.

The aim of the dose escalation phase is to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of AFM24 in combination with atezolizumab.

The dose escalation phase will be followed by the expansion phase once the MTD/RP2D of AFM24 in combination with atezolizumab has been determined. The expansion phase of the study is intended to collect preliminary evidence of efficacy and to further confirm the safety of 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 chemotherapy and PD1/PD-L1 targeted therapy
* Gastric/GEJ cancer if intolerant to or with disease progression after standard platinum-based chemotherapy
* Pancreatic/hepatocellular/biliary tract cancer with disease progression after standard of care (SOC) therapy or if there is no appropriate SOC available for their condition
* Advanced or metastatic NSCLC harboring a targetable EGFR kinase domain mutation with disease progression on or after received ≥1 prior lines of treatment for advanced disease, including a Tyrosine-Kinase Inhibitor (TKI) for EGFR mutations

Study to Assess AFM24 in Combination With Atezolizumab in Selected Advanced/Metastatic EGFR-expressing Cancers

A Phase 1/2a Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AFM24 in Combination With Atezolizumab in Patients With Selected Advanced/Metastatic EGFR-expressing Cancers

The number of patients with dose limiting toxicities (DLTs) in the first cycle, as assessed by the National Cancer Institute Common Technology Criteria for Adverse Events (CTCAE) v5.0

Incidence of patients with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Area under the concentration-time curve over the dose interval (AUCtau)

Measurement of ADAs before and during treatment with AFM24 in combination with atezolizumab

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antirheumatic Agents

Anti-Infective Agents

Paclitaxel

Carboplatin

Cyclophosphamide

Albumin-Bound Paclitaxel

Epirubicin

Immunomodulating Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles.

12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles.

Atezolizumab 1200 MG in 20 ML Injection

Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles

Paclitaxel 80 mg/m² IV weekly x 12 cycles

1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter.

Biopsy Arm A

1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter.

Biopsy Arm B

After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Surgery

Iris Reiser, Dr.

Hans-Christian Kolberg, Prof. Dr.

This is a randomized, open-label, adaptive, two arm, multicentre, Phase II trial comparing a neoadjuvant chemotherapy with PDL1-inhibition (Atezolizumab) and Atezolizumab two-week window to chemotherapy with PDL1-inhibition (Atezolizumab) and identify biomarkers predicting (early) response to or resistance against Atezolizumab (alone and with CTX) allowing patients stratification in future clinical trials

Study to Compare a Mono Atezolizumab Window Followed by a Atezolizumab - CTX Therapy With Atezolizumab - CTX Therapy

An Adaptive Randomized Neoadjuvant Two Arm Trial in Triple-negative Breast Cancer Comparing a Mono Atezolizumab Window Followed by a Atezolizumab - CTX Therapy With Atezolizumab - CTX Therapy (neoMono)

Pathological Complete Response defined as no residual invasive tumor cells in the breast and in the lymph nodes (ypT0/is, ypN0)

Safety (incidence, relationship, seriousness, and severity of all AEs, SAEs, AESIs coded by medical dictionary for regulatory activities (MedDRA), summarized by Preferred Term and System Organ Class and graded according to common terminology criteria of adverse events (CTCAE V5.0)

Pathological complete response defined as no residual invasive tumor cells in the breast and in the lymph nodes (ypT0/is, ypN0) in patients with an ER/PR expression of \<1% and an ER/PR expression of 1% to 10%.

Pathological complete response defined as no tumor cells (invasive and no non-invasive) in the breast but also in the lymph nodes (ypN0, ypT0)

Near pCR defined as residual tumor \<5 mm in the breast irrespective of in situ and lymph nodes status

Pathological Complete Response defined as no invasive tumor in the breast, irrespective of lymph node status

Decrease of Ki-67 expression versus baseline after 14/28 days (+/- 2 days) of treatment as continuous predictor

TILs after 14/28 days (+/- 2 days) of treatment as continuous predictor

CCCA: Ki-67 expression ≤ 2.7% after 14/28 days (+/- 2 days) of treatment

Low cellularity: \< 500 tumor cells after 14/28 days (+/- 2 days) of treatment

Decrease of Ki-67 expression versus baseline by 30% or more after 14/28 days (+/- 2 days) of treatment

TILs ≥ 60% after 14/28 days (+/- 2 days) of treatment

Combined early response defined by

* CCCA (Ki-67 expression \< 2.7%) or
* low cellularity or
* decrease of Ki-67 expression (versus baseline) by 30% or more or
* TILs ≥ 60%

Disease free survival (DFS) defined as time from the first date of no disease \[i.e. date of surgery\] to the first occurrence of disease recurrence or death from any cause

Overall survival (OS) defined as length of time from randomization to death from any cause

Event free survival (EFS) defined as length of time after randomization till death from any cause, failure to achieve remission after induction therapy, relapse in any site, or second malignancy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Assess AFM24 in Combination With Atezolizumab in Selected Advanced/Metastatic EGFR-expressing Cancers	NCT05109442	Advanced Solid ...	AFM24 Atezolizumab 84...	18 Years -	Affimed GmbH
Study to Compare a Mono Atezolizumab Window Followed by a Atezolizumab - CTX Therapy With Atezolizumab - CTX Therapy	NCT04770272	Triple-negative...	Atezolizumab 84... Atezolizumab 12... Carboplatin Paclitaxel Epirubicin Cyclophosphamid... Biopsy Arm A Biopsy Arm B Surgery	18 Years -	Palleos Healthcare GmbH
Study to Assess AFM24 in Combination With Atezolizumab in Selected Advanced/Metastatic EGFR-expressing Cancers	NCT05109442	Advanced Solid ...	AFM24 Atezolizumab 84...	18 Years -	Affimed GmbH

Spots Global Cancer Trial Database for atezolizumab 840 mg in 14 ml injection