Study of IGM-8444 as a Single Agent and in Combination With Chemotherapy-based Regimens in Subjects With Solid Cancers

An Open-label, Multicenter, Phase I Study of IGM-8444 as a Single Agent and in Combination With Chemotherapy-based Regimens in Subjects With Relapsed and/or Refractory Solid Cancers

Sponsoren

Hauptsponsor: IGM Biosciences, Inc.

Quelle IGM Biosciences, Inc.
Kurze Zusammenfassung

This study is a first-in-human, Phase 1, multicenter, open-label study to determine the safety, tolerability and pharmacokinetics of IGM-8444 as a single agent and in combination with a chemotherapy-based regimen in patients with relapsed and/or refractory solid tumors.

detaillierte Beschreibung

Patients will be enrolled in two stages: a dose-escalation stage and an expansion stage. The escalation stage will investigate single agent IGM-8444 in patients with solid tumors and IGM-8444 in combination with FOLFIRI for colorectal carcinoma patients. The IGM-8444 single agent expansion cohort will enroll the following tumor types: colorectal carcinoma, gastric, non-small cell lung cancer, sarcoma, and an all-comers cohort which will include relapsed/refractory non-hodgkins lymphoma patients. The IGM-8444 + FOLFIRI with or without bevacizumab combination expansion cohorts will enroll colorectal carcinoma patients. IGM-8444 will be administered intravenously (IV). An alternative dosing schedule may be evaluated.

Gesamtstatus Recruiting
Anfangsdatum September 2020
Fertigstellungstermin October 2023
Primäres Abschlussdatum August 2023
Phase Phase 1
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Adverse Events of IGM-8444 as a single agent as single agent and in combination with FOLFIRI +/- bevacizumab. 8 weeks
Recommended Phase 2 Dose (RP2D) of IGM-8444 as a single agent as single agent and in combination with FOLFIRI +/- bevacizumab. 4 weeks
Sekundäres Ergebnis
Messen Zeitfenster
Area Under the Curve (AUC) of IGM-8444 At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Clearance (CL) of IGM-8444 At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Volume of distribution (V) of IGM-8444 At pre-defined intervals from Cycle 1 Day 1 through end of treatment at approximately 6 months
Immunogenicity through end of treatment at approximately 6 months
Objective Response Rate (ORR) Study duration of approximately 36 months
Duration of Response (DoR) Study duration of approximately 36 months
Progression-Free Survival (PFS) Study duration of approximately 36 months
Einschreibung 230
Bedingung
Intervention

Interventionsart: Drug

Interventionsname: IGM-8444

Beschreibung: DR5 Agonist Investigational Drug

Interventionsart: Drug

Interventionsname: FOLFIRI

Beschreibung: Chemotherapy Regimen

Interventionsart: Drug

Interventionsname: Bevacizumab

Beschreibung: Targeted Therapy

Armgruppenetikett: IGM-8444 + FOLFIRI + Bevacizumab Expansion

Anderer Name: Avastin

Teilnahmeberechtigung

Kriterien:

Key Inclusion Criteria:

- Age ≥ 18 years at time of signing Informed Consent Form

- Life expectancy of at least 12 weeks

- ECOG Performance Status of 0 or 1

- Patients who are either refractory to or intolerant of existing standard therapy or for whom no effective further standard of care therapy exists.

- No more than three prior therapeutic regimens ("therapeutic" is defined as any cytotoxic, biologic, or targeted therapy [approved or investigational] with intent to treat the cancer) administered for the treatment of cancer in the advanced/metastatic setting.

- For dose escalation cohorts only: Patients with either measurable or evaluable disease.

- Patients with histologic documentation of incurable, locally advanced or metastatic prostate cancer with non-measurable disease are eligible if they have an increase in prostate-specific antigen (PSA) level of > 50% from current level, the absolute increase is ≥ 5 ng/mL, and the increase is confirmed a second time.

- Patients with histologic documentation of incurable, locally advanced or metastatic ovarian cancer with non-measurable disease are eligible if they have an increase of > 2 × the baseline level in CA-125 (or > 2 × the ULN in case of prior normal CA-125 level) and the increase is confirmed a second time.

- Adequate organ function as evidenced by (hematologic parameters must be assessed at least 14 days from the last growth factor support or prior transfusion, if any):

- ANC ≥ 1000/μL.

- Total hemoglobin ≥ 9 g/dL.

- Platelet count ≥ 100,000/μL.

- Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or estimated creatinine clearance ≥ 50 mL/min (Cockcroft Gault or other institutional methods).

- Serum aspartate transaminase (AST) and serum ALT ≤ 2 × ULN.

- AST and ALT ≤ 3 × ULN is allowed if liver function abnormalities are due to underlying malignancy.

- Total serum bilirubin ≤ 1.5 × ULN regardless of liver involvement secondary to tumor.

- Inclusion of patients with increased serum indirect bilirubin (≤ 3 × ULN) due to Gilbert's syndrome is permitted.

- Alkaline phosphatase ≤ 2.5 × the ULN

- Albumin ≥3.0 g/dL.

- No clinically significant pleural or peritoneal effusion requiring drainage.

Key Exclusion Criteria:

- Prior DR5 agonist therapy.

- Prior Bcl-family inhibitor therapy

- Concomitant use of agents well-known to cause liver toxicity.

- Known clinically significant history of liver disease including Child-Pugh Class B or C, including active viral or other hepatitis (e.g., hepatitis B or hepatitis C virus), current alcohol abuse, non-alcoholic steatohepatitis (NASH), or cirrhosis.

- Diagnosis of any secondary malignancy within 3 years prior to enrollment

- Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control).

- Current Grade > 1 toxicity (except alopecia and anorexia) from prior therapy. Patients with current Grade 2 chronic toxicities that are well-controlled by medications may be enrolled after discussion with medical monitor.

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: N/A

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Eric Humke, MD, PhD Study Director IGM Biosciences
Gesamtkontakt

Nachname: Clinical Trials

Telefon: 650 265 6428

Email: [email protected]

Ort
Einrichtung: Status: Kontakt: SCRI - Tennessee Clinical Trials [email protected]
Standort Länder

United States

Überprüfungsdatum

September 2020

Verantwortliche Partei

Art: Sponsor

Schlüsselwörter
Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 6
Armgruppe

Etikette: IGM-8444 Single Agent Escalation

Art: Experimental

Beschreibung: IGM-8444 will be administered intravenously as a single agent.

Etikette: IGM-8444 Single Agent Alternate Dosing Escalation

Art: Experimental

Beschreibung: IGM-8444 will be administered intravenously as a single agent on an alternate dosing schedule.

Etikette: IGM-8444 + FOLFIRI Escalation

Art: Experimental

Beschreibung: IGM-8444 will be administered intravenously in combination with FOLFIRI.

Etikette: IGM-8444 Single Agent Expansion

Art: Experimental

Beschreibung: IGM-8444 will be administered intravenously as a single agent in disease specific cohorts.

Etikette: IGM-8444 + FOLFIRI Expansion

Art: Experimental

Beschreibung: IGM-8444 will be administered intravenously in combination with FOLFIRI.

Etikette: IGM-8444 + FOLFIRI + Bevacizumab Expansion

Art: Experimental

Beschreibung: IGM-8444 will be administered intravenously in combination with FOLFIRI with bevacizumab.

Studiendesign Info

Zuweisung: Non-Randomized

Interventionsmodell: Sequential Assignment

Hauptzweck: Treatment

Maskierung: None (Open Label)

Quelle: ClinicalTrials.gov