Combination of Gatipotuzumab and Tomuzotuximab in Patients With Solid Tumors

NCT03360734 | Completed Phase 1

• 2 other identifiers: 52251012017-001609-33
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 4

Brief Summary

This was a single arm phase Ib study to evaluate the safety and efficacy of combined Tomuzotuximab and Gatipotuzumab therapy in patients with metastatic solid tumors expressing EGFR for whom no standard treatment is available. Patients who had relapsed following their most recent line of chemotherapy and who met all other entry criteria at Screening were enrolled to receive Tomuzotuximab and Gatipotuzumab in combination. During the extension phase, instead of Tomuzotuximab a commercially avalaible anti-EGFR antibody, i.e. Cetuximab (including any approved biosimilar), Panitumumab, or Necitumumab could be given to patients with cancers for which their use is approved.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (2)

• Safety: Incidence and Severity of adverse events (AEs) and IRRs

  Incidence of adverse events (AEs) and IRRs

  12 months

• Overall tolerability

  Standard safety assessments in terms of laboratory evaluations, vital signs, electrocardiogram \[ECG\], and physical examinations

  12 months

Secondary Outcomes (3)

• Efficacy of the combined treatment: Objective response rate (ORR)

  12 months

• Immunogenicity of combined Treatment: incidence of anti-drug antibodies (ADAs)

  12 months

• Pharmacokinetics (PK) of combined Treatment: Concentration

  12 months

Study Arms (1)

Combination

EXPERIMENTAL

First part: Combination of Gatipotuzumab (GAT) and Tomuzotuximab (TOM) Treatment: 5 weeks monotherapy with TOM (Day 1: 60mg, Day 2: 660mg, Week 2: 1200mg, Week 4: 1200mg). Then combination of 1200mg TOM with 1400mg of GAT every two weeks until disease progression, as long as patient does not meet any other discontinuation criterion such as unacceptable toxicity. Second part: Combination of GAT and TOM or an approved anti-EGFR antibody, i.e. Cetuximab, Panitumumab, or Necitumumab Treatment: One week monotherapy with TOM (Week 1, Day 1: 60mg, Day 2: 660mg). Then 1200mg TOM in combination with 1400mg of GAT every two weeks until disease progression, as long as patient does not meet any other discontinuation criterion such as unacceptable toxicity or commercial anti-EGFR antibody (dosage according to local practices) in combination with 1400mg of GAT every two weeks until disease progression or until unacceptable toxicity

Drug: First part: Gatipotuzumab and Tomuzotuximab; Second part: Gatipotuzumab and Tomuzotuximab or anti-EGFR antibody (Cetuximab, Panitumumab or Necitumumab)

Interventions

First part: Gatipotuzumab and Tomuzotuximab; Second part: Gatipotuzumab and Tomuzotuximab or anti-EGFR antibody (Cetuximab, Panitumumab or Necitumumab) DRUG

Two monoclonal antibodies, Gatipotuzumab is anti-TAMUC1, Tomuzotuximab is anti-EGFR

Also known as: PankoMab-GEX (GAT) and CetuGEX (TOM)

Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female and age ≥18 years
• Histologically confirmed locally advanced and/or metastatic solid organ tumor including but not limited to the following histology: Non-Small Cell Lung cancer (NSCLC), Gastrointestinal cancer (GI), Breast cancer (BC), Gynecological cancers (GYN). Date of histology should be not older than 18 months from the start of the screening procedures. Additionally 30 patients will be enrolled in 4 expansion cohorts: 1) refractory metastatic Colorectal cancer (mCRC) patients who have failed prior treatment with standard chemotherapeutics and both anti-VEGF and anti-EGFR antibodies; 2) patients with recurrent and/or metastatic Head and Neck cancers, who have failed prior treatment with a checkpoint inhibitor and at least one line of chemotherapy as appropriate depending on the histology and platinum-elegibility; salivary gland tumors can be enrolled in this cohort after failure of at least one line of chemotherapy; 3) refractory metastatic NonSmall Cell Lung cancer (NSCLC) patients who have failed all standard treatment options including chemotherapy, tyrosine kinase inhibitors and immunotherapy as appropriate depending on the histology and mutational status, 4) refractory metastatic Breast cancer (BC) patients who have failed all standard treatment options including chemotherapy, hormone therapy and anti-human epidermal growth factor receptor 2 \[HER2\] treatment as appropriate depending on the histology.
• Patients are required to have a positive EGFR IHC expression (≥25% of tumor cells) as assessed by local laboratory. This condition will not be required anymore in the additional 30 patients of the expansion cohorts
• Measurable disease according to RECIST 1.1. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have a short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines
• Failure of standard therapy or non-availability of standard therapy (patients must have received at least one line of chemotherapy and further standard therapy is not an option at study entry)
• Prior treatment with any anti-EGFR agent should be completed at least 4 months before start of treatment. This condition will no longer be required in the 30 additional patients of the expansion cohorts.
• Toxicities, except for alopecia and Grade 2 neuropathy, should be not greater than Grade 1 before start of treatment according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE \[v. 4.0\])
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 and estimated life expectancy of ≥3 months
• Adequate organ function as evidenced by the following:
• Bone marrow function: hemoglobin ≥90 g/L; white blood cell (WBC) count ≥3.0 x 109/L; absolute neutrophil count (ANC) ≥1.0 x 109/L; platelet count ≥75 x 109/L
• Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) (≤5 x ULN if hepatic metastases present); bilirubin ≤1.5 x ULN; alkaline phosphatase ≤5.0 x ULN
• Renal function: creatinine \<1.5 x ULN
• Cardiologic function: LVEF fraction ≥ 50% assessed by radionuclide angiography (MUGA scan) or Echocardiography
• Patients of both genders with procreative potential must use effective contraception while enrolled in the study and for at least 6 months (for women) or 16 weeks (for men) after the last study drug infusion
• Written informed consent obtained prior to conducting any study specific procedures

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Glycotope staff and/or staff at the study site)
• Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
• Patients institutionalized by official means or court order.
• Chemotherapy, radiation, or any other anti-cancer therapies, including any investigational agent, within 4 weeks prior start of study treatment
• Concurrent anti-tumor therapy or concurrent immunotherapy
• Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Major surgery within 4 weeks prior to entering the study and/or incomplete recovery from surgery or planned major surgery
• Primary or secondary immune deficiency requiring treatment. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician

Sponsors & Collaborators

• Glycotope GmbH: lead

Study Sites (4)

Glycotope-contracted research facility

Berlin, 1xxxx, Germany

Location

Glycotope-contracted research facility

Hamburg, 2xxxx, Germany

Location

Glycotope-contracted research facility

Milan, 2xxxx, Italy

Location

Glycotope-contracted research facility

Barcelona, xxxxx, Spain

Location

Related Publications (1)

• Ochsenreither S, Fiedler WM, Conte GD, Macchini M, Matos I, Habel B, Ahrens-Fath I, Raspagliesi F, Lorusso D, Keilholz U, Rolling C, Kebenko M, Klinghammer KF, Saavedra O, Baumeister H, Zurlo A, Garralda E. Safety and preliminary activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab in patients with refractory solid tumors. ESMO Open. 2022 Apr;7(2):100447. doi: 10.1016/j.esmoop.2022.100447. Epub 2022 Apr 6.

  PMID: 35397434 DERIVED

MeSH Terms

Interventions

Cetuximab; Panitumumab; necitumumab; PankoMab-GEX; GAT

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sebastian Ochsenreither, Dr. med.

  Charité Benjamin Franklin Comprehensive Cancer Center,Hindenburgdamm 30,12200/12203 Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: December 4, 2017
• Study Start: November 2, 2017
• Primary Completion: May 4, 2020
• Study Completion: September 29, 2020
• Last Updated: July 12, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); DE (2); IT (1)