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

• ClinicalTrials.gov Identifier: NCT03798626
• Recruitment Status: Active, not recruiting
• First Posted: January 10, 2019
• Last Update Posted: May 3, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer; Gastroesophageal Cancer; Renal Cell Carcinoma	Drug: Gevokizumab; Drug: Bevacizumab; Drug: Modified FOLFOX6; Drug: FOLFIRI; Drug: Ramucirumab; Drug: Paclitaxel; Drug: Cabozantinib	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 168 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 22, 2019
• Actual Primary Completion Date: March 1, 2023
• Estimated Study Completion Date: October 28, 2024

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: VPM087; Drug: Cabozantinib; 60 mg tablet; administered orally

Outcome Measures

Primary Outcome Measures :

1. Part 1a (Dose finding): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy [ Time Frame: Baseline, Day 15 ]
   Log scale change of hs-CRP at Day 15 from baseline
2. Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D] [ Time Frame: First 4 weeks of combination treatment ]
   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.
3. Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B] [ Time Frame: First 6 weeks of combination treatment ]
   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.
4. Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level] [ Time Frame: At 15 months ]
   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.
5. Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level] [ Time Frame: At 9 months ]
   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.
6. Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level] [ Time Frame: At 6 months ]
   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.

Secondary Outcome Measures :

1. Overall response rate (ORR) per investigator assessment using RECIST v1.1 [ Time Frame: Up to 5 years ]
   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
2. Duration of response (DOR) per investigator assessment using RECIST v1.1 [ Time Frame: Up to 5 years ]
   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
3. Disease Control Rate (DCR) per investigator assessment using RECIST v1.1 [ Time Frame: Up to 5 years ]
   DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.
4. Overall survival (OS) [ Time Frame: Up to 5 years ]
   OS is defined as the time from date of first dose of study treatment to date of death due to any cause.
5. PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level] [ Time Frame: Up to 5 years ]
   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.
6. PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B) [ Time Frame: Up to 5 years ]
   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.
7. Serum concentration of gevokizumab, as monotherapy and in the combination regimens [ Time Frame: Up to 5 years ]
   To characterize the pharmacokinetics of gevokizumab therapy
8. Serum concentration of bevacizumab [ Time Frame: Up to 5 years ]
   To characterize the pharmacokinetics of bevacizumab therapy
9. Serum concentration of ramucirumab [ Time Frame: Up to 5 years ]
   To characterize the pharmacokinetics of ramucirumab therapy
10. Serum concentration of irinotecan [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of irinotecan therapy
11. Serum concentration of paclitaxel [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of paclitaxel therapy
12. Serum concentration of cabozantinib [ Time Frame: Up to 3 months ]
    To characterize the pharmacokinetics of cabozantinib therapy
13. Number of patients with anti-drug antibodies for gevokizumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for gevokizumab
14. Number of patients with anti-drug antibodies for bevacizumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for bevacizumab
15. Number of patients with anti-drug antibodies for ramucirumab in the combination regimens [ Time Frame: Up to 5 years ]
    Incidence of immunogenicity for ramucirumab

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• 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.

For Cohort A:

- First line metastatic colorectal cancer.

For Cohort B:

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

For Cohort C:

- Second line metastatic gastroesophageal cancer 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.
• 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.

Exclusion Criteria:

For All Cohorts:

• Currently receiving any of the prohibited medications or has contraindications as outlined in the protocol.
• 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

Contacts and Locations

Locations

United States, California

UCLA Medical Center UCLA Oncology Clinic

Los Angeles, California, United States, 90095

United States, Missouri

Washington University School of Medicine Siteman Cancer Center

Saint Louis, Missouri, United States, 63110

United States, Tennessee

Sarah Cannon Research Institute Drug Ship - 4

Nashville, Tennessee, United States, 37203

Australia, Victoria

Novartis Investigative Site

Melbourne, Victoria, Australia, 3000

Belgium

Novartis Investigative Site

Edegem, Antwerpen, Belgium, 2650

Novartis Investigative Site

Bruxelles, Belgium, 1000

Novartis Investigative Site

Leuven, Belgium, 3000

Canada, Alberta

Novartis Investigative Site

Calgary, Alberta, Canada, T2N 4N2

Canada, Ontario

Novartis Investigative Site

Toronto, Ontario, Canada, M5G 1Z6

Chile

Novartis Investigative Site

Santiago, Chile, 8330074

Czechia

Novartis Investigative Site

Brno, Czech Republic, Czechia, 656 53

Germany

Novartis Investigative Site

Dresden, Germany, 01307

Novartis Investigative Site

Frankfurt, Germany, 60488

Novartis Investigative Site

Ulm, Germany, 89081

Israel

Novartis Investigative Site

Ramat Gan, Israel, 52621

Novartis Investigative Site

Tel Aviv, Israel, 6423906

Italy

Novartis Investigative Site

Milano, MI, Italy, 20162

Novartis Investigative Site

Rozzano, MI, Italy, 20089

Japan

Novartis Investigative Site

Nagoya, Aichi, Japan, 464 8681

Novartis Investigative Site

Kashiwa, Chiba, Japan, 277 8577

Novartis Investigative Site

Osaka-city, Osaka, Japan, 541-8567

Novartis Investigative Site

Sunto Gun, Shizuoka, Japan, 411 8777

Novartis Investigative Site

Bunkyo-ku, Tokyo, Japan, 113-8603

Korea, Republic of

Novartis Investigative Site

Seoul, Korea, Republic of, 05505

Singapore

Novartis Investigative Site

Singapore, Singapore, 119074

Spain

Novartis Investigative Site

Sevilla, Andalucia, Spain, 41013

Novartis Investigative Site

Hospitalet de LLobregat, Catalunya, Spain, 08907

Novartis Investigative Site

Valencia, Comunidad Valenciana, Spain, 46010

Novartis Investigative Site

Madrid, Spain, 28009

Novartis Investigative Site

Madrid, Spain, 28034

Novartis Investigative Site

Madrid, Spain, 28050

Taiwan

Novartis Investigative Site

Tainan, Taiwan, 70403

United Kingdom

Novartis Investigative Site

London, United Kingdom, SW3 6JJ

Novartis Investigative Site

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03798626
• Other Study ID Numbers: CVPM087A2101; 2018-003952-19 ( EudraCT Number )
• First Posted: January 10, 2019
• Last Update Posted: May 3, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Carcinoma; Colorectal Neoplasms; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Leucovorin; Paclitaxel; Bevacizumab; Fluorouracil; Oxaliplatin