Gevokizumab With Standard of Care Anti-cancer Therapies for Metastatic Colorectal, Gastroesophageal, and Renal Cancers

Phase Ib Study of Gevokizumab in Combination With Standard of Care Anti-cancer Therapies in Patients With Metastatic Colorectal Cancer, Gastroesophageal Cancer and Renal Cell Carcinoma

This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose of gevokizumab in combination with the standard of care anti-cancer therapy in patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic renal cell carcinoma, and the preliminary efficacy of gevokizumab in combination with the SOC anti-cancer therapy in subjects with mCRC and mGEC.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma; Colorectal Cancer; Gastroesophageal Cancer
• Intervention / Treatment: Drug: Gevokizumab; Drug: Bevacizumab; Drug: Modified FOLFOX6; Drug: FOLFIRI; Drug: Ramucirumab; Drug: Paclitaxel; Drug: Cabozantinib

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
• Belgium
  • Brussels, Belgium, 1000
    • Novartis Investigative Site
  • Edegem, Belgium, 2650
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N2
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 8330074
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 656 53
    • Novartis Investigative Site
• Germany
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60488
      • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
• Israel
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • MI
    • Milan, MI, Italy, 20162
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464 8681
      • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 2778577
      • Novartis Investigative Site
  • Osaka
    • Osaka, Osaka, Japan, 5418567
      • Novartis Investigative Site
  • Shizuoka
    • Sunto Gun, Shizuoka, Japan, 411 8777
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 05505
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28050
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Seville, Spain, 41013
    • Novartis Investigative Site
  • Valencia, Spain, 46010
    • Novartis Investigative Site
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
• Taiwan
  • Tainan, Taiwan, 704302
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 2BX
    • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California LA
  • Missouri
    • St Louis, Missouri, United States, 63110
      • WA Uni School Of Med
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

For All Cohorts:

• Adult ≥ 18 years old.
• Metastatic disease not amenable to potentially curative surgery and with available archival tumor tissue or fresh tumor tissue biopsy.
• Presence of at least 1 measurable lesion assessed by CT and/or MRI according to RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Adequate bone marrow and organ function per defined criteria in the protocol.
• Recovered from acute laboratory and clinical toxicities of prior anti cancer treatment to NCI CTCAE v5.0 grade ≤1 at time of screening, except alopecia and amenorrhea.

For Cohort A:

• First line metastatic colorectal adenocarcinoma.

For Cohort B:

• Second line metastatic colorectal adenocarcinoma that has progressed on prior line of chemotherapy administered for metastatic disease and which must include a fluoropyrimidine and oxaliplatin.

For Cohort C:

• Second line metastatic gastroesophageal adenocarcinoma that has progressed on prior line of chemotherapy administered for metastatic disease, and which must include a platinum agent and fluoropyrimidine doublet.

For Cohort D:

• Second or third line metastatic renal cell carcinoma with a clear cell component and has received one or two lines of treatment for metastatic disease that included an anti angiogenic agent for at least 4 weeks with radiologic progression on that treatment.

For subjects starting from Part 1a in Cohorts A and B:

• Serum hs CRP at screening ≥ 10 mg/L (per central laboratory assessment).
• Not requiring immediate initiation of anti cancer therapy per investigator's best judgement.

For subjects starting from Part 2 in Cohort C:

• Serum hs CRP at screening ≥ 10 mg/L (per central laboratory assessment).

Key Exclusion Criteria:

For All Cohorts:

• Currently receiving any of the prohibited medications or has contraindications as outlined in the 'Contraindications' to SOC regimen components.
• Symptomatic brain metastases or brain metastases that require directed therapy (such as focal radiotherapy or surgery).
• Suspected or proven immunocompromised state, or infections (as defined in the protocol).
• Conditions that have a high risk of clinically significant bleeding after administration of anti VEGF agents.
• Clinically significant, uncontrolled or recent (within last 6 months) cardiovascular disease.

For Cohort D:

• Concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5, and medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
• Impairment of GI function or GI disease that may significantly alter the absorption of cabozantinib.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: 1st line colorectal cancer; Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab	Drug: Gevokizumab; 60 mg/mL concentration; administered intravenously (IV); Other Names: VPM087; Drug: Bevacizumab; 25 mg/mL concentration; administered IV; Drug: Modified FOLFOX6; Oxaliplatin [5 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV]; Other Names: oxaliplatin, leucovorin, 5-fluorouracil
Experimental: Cohort B: 2nd line colorectal cancer; Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab	Drug: Gevokizumab; 60 mg/mL concentration; administered intravenously (IV); Other Names: VPM087; Drug: Bevacizumab; 25 mg/mL concentration; administered IV; Drug: FOLFIRI; Irinotecan [20 mg/mL concentration; administered IV], leucovorin [10 mg/mL concentration; administered IV] (or levoleucovorin [10 mg/mL concentration; administered IV]), and 5-fluorouracil [50 mg/mL concentration; administered IV]; Other Names: irinotecan, leucovorin, 5-fluorouracil
Experimental: Cohort C: 2nd line gastroesophageal cancer; Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab	Drug: Gevokizumab; 60 mg/mL concentration; administered intravenously (IV); Other Names: VPM087; Drug: Ramucirumab; 10 mg/mL concentration; administered IV; Drug: Paclitaxel; 6 mg/mL concentration; administered IV
Experimental: Cohort D: 2nd or 3rd line renal cell carcinoma; Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib	Drug: Gevokizumab; 60 mg/mL concentration; administered intravenously (IV); Other Names: VPM087; Drug: Cabozantinib; 60 mg tablet; administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D]	DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.	First 4 weeks of combination treatment
Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B]	DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.	First 6 weeks of combination treatment
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level]	PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.	At 15 months
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level]	PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.	At 9 months
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level]	PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.	At 6 months
Part 1a/b (Cohorts A and B): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy	Log scale change of hs-CRP at Day 15 from baseline	Baseline, Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) per investigator assessment using RECIST v1.1	ORR is defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), according to RECIST 1.1	Up to 5 years
Duration of response (DOR) per investigator assessment using RECIST v1.1	Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria	Up to 5 years
Disease Control Rate (DCR) per investigator assessment using RECIST v1.1	DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.	Up to 5 years
Overall survival (OS)	OS is defined as the time from date of first dose of study treatment to date of death due to any cause.	Up to 5 years
PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level]	PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.	Up to 5 years
PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B)	PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.	Up to 5 years
Number of patients with anti-drug antibodies for gevokizumab in the combination regimens	Incidence of immunogenicity for gevokizumab	Up to 5 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Novartis Pharma AG results
• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2019
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): February 5, 2025

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: colorectal cancer; bevacizumab; paclitaxel; cabozantinib; renal cell carcinoma; CRC; ramucirumab; gastroesophageal cancer; FOLFIRI; RCC; gevokizumab; modified FOLFOX6; GEC; VPM087
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Colonic Diseases; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Colorectal Neoplasms; Carcinoma, Renal Cell; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Bevacizumab; Irinotecan; Ramucirumab; Fluorouracil; Leucovorin; Paclitaxel; cabozantinib; IFL protocol; gevokizumab
• Other Study ID Numbers: CVPM087A2101; 2018-003952-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No