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

NCT03798626 | Completed Phase 1 FDA Drug

• 2 other identifiers: CVPM087A21012018-003952-19
• Study Type: interventional
• Target: 167
• Locations: 15 countries
• Sites: 34

Brief Summary

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.

Conditions

Gastroesophageal Cancer; Renal Cell Carcinoma; Colorectal Cancer

Keywords

colorectal cancer; gastroesophageal cancer; renal cell carcinoma; gevokizumab; bevacizumab; modified FOLFOX6; FOLFIRI; ramucirumab; paclitaxel; cabozantinib; CRC; GEC; RCC; VPM087

Outcome Measures

Primary Outcomes (6)

• 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

• 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

Secondary Outcomes (7)

• Overall response rate (ORR) per investigator assessment using RECIST v1.1

  Up to 5 years

• Duration of response (DOR) per investigator assessment using RECIST v1.1

  Up to 5 years

• Disease Control Rate (DCR) per investigator assessment using RECIST v1.1

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

• PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level]

  Up to 5 years

Study Arms (4)

Cohort A: 1st line colorectal cancer

EXPERIMENTAL

Treatment for 1st line metastatic colorectal cancer (mCRC) with Gevokizumab, modified FOLFOX6, bevacizumab

Drug: Gevokizumab; Drug: Bevacizumab; Drug: Modified FOLFOX6

Cohort B: 2nd line colorectal cancer

EXPERIMENTAL

Treatment for 2nd line mCRC with Gevokizumab, FOLFIRI, bevacizumab

Drug: Gevokizumab; Drug: Bevacizumab; Drug: FOLFIRI

Cohort C: 2nd line gastroesophageal cancer

EXPERIMENTAL

Treatment for 2nd line metastatic gastroesophageal cancer (mGEC) with Gevokizumab, paclitaxel, ramucirumab

Drug: Gevokizumab; Drug: Ramucirumab; Drug: Paclitaxel

Cohort D: 2nd or 3rd line renal cell carcinoma

EXPERIMENTAL

Treatment for 2nd or 3rd line metastatic renal cell carcinoma (mRCC) with Gevokizumab, cabozantinib

Drug: Gevokizumab; Drug: Cabozantinib

Interventions

Bevacizumab DRUG

25 mg/mL concentration; administered IV

Cohort A: 1st line colorectal cancer; Cohort B: 2nd line colorectal cancer

FOLFIRI DRUG

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 \[50 mg/mL concentration; administered IV\]

Also known as: irinotecan, leucovorin, 5-fluorouracil

Cohort B: 2nd line colorectal cancer

Ramucirumab DRUG

10 mg/mL concentration; administered IV

Cohort C: 2nd line gastroesophageal cancer

Paclitaxel DRUG

6 mg/mL concentration; administered IV

Cohort C: 2nd line gastroesophageal cancer

Cabozantinib DRUG

60 mg tablet; administered orally

Cohort D: 2nd or 3rd line renal cell carcinoma

Gevokizumab DRUG

60 mg/mL concentration; administered intravenously (IV)

Also known as: VPM087

Cohort A: 1st line colorectal cancer; Cohort B: 2nd line colorectal cancer; Cohort C: 2nd line gastroesophageal cancer; Cohort D: 2nd or 3rd line renal cell carcinoma

Modified FOLFOX6 DRUG

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 \[50 mg/mL concentration; administered IV\]

Also known as: oxaliplatin, leucovorin, 5-fluorouracil

Cohort A: 1st line colorectal cancer

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (34)

University of California LA

Los Angeles, California, 90095, United States

Location

WA Uni School Of Med

St Louis, Missouri, 63110, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Edegem, 2650, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Calgary, Alberta, T2N4N2, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Santiago, Santiago Metropolitan, 8330074, Chile

Location

Novartis Investigative Site

Brno, 656 53, Czechia

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60488, Germany

Location

Novartis Investigative Site

Dresden, Saxony, 01307, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Ramat Gan, 5265601, Israel

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 464 8681, Japan

Location

Novartis Investigative Site

Kashiwa, Chiba, 2778577, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 5418567, Japan

Location

Novartis Investigative Site

Sunto Gun, Shizuoka, 411 8777, Japan

Location

Novartis Investigative Site

Bunkyo-ku, Tokyo, 113-8603, Japan

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Novartis Investigative Site

Seville, 41013, Spain

Location

Novartis Investigative Site

Valencia, 46010, Spain

Location

Novartis Investigative Site

Tainan, 704302, Taiwan

Location

Novartis Investigative Site

London, SW3 6JJ, United Kingdom

Location

Novartis Investigative Site

Manchester, M20 2BX, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Renal Cell

Interventions

gevokizumab; Bevacizumab; Oxaliplatin; Leucovorin; Fluorouracil; IFL protocol; Irinotecan; Ramucirumab; Paclitaxel; cabozantinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 10, 2019
• Study Start: May 22, 2019
• Primary Completion: March 1, 2023
• Study Completion: February 5, 2025
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); CZ (1); JP (5); US (3); SG (1); CL (1); ES (6); DE (3); KR (1); BE (3); IL (2); AU (1); CA (2); TW (1); GB (2)