Clinical Trial 23448

• Overview

  Study Title:

  A Phase 1 Trial Evaluating the Safety, Tolerability, PK, and Efficacy of QTX3034 in Patients with Solid Tumors with KRASG12D Mutation

  Objective:

  Primary Objectives: * Evaluate the safety and tolerability of QTX3034 in adult patients with KRASG12D solid tumors as monotherapy, and in combination with cetuximab * Determine the maximum tolerated dose and/or recommended phase 2 dose of QTX3034 as monotherapy and in combination with cetuximab Secondary Objectives: * Characterize the PK profile of QTX3034 following oral administration as monotherapy and in combination with cetuximab * Evaluate preliminary antitumor activity of QTX3034 as monotherapy and in combination with cetuximab in subsets of patients with specific tumor types

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy; Therapy (NOS)

  Medications:

  Cemiplimab (); Cetuximab (); Erbitux (Cetuximab); Pembrolizumab (Keytruda); QTX3034 (); REGN2810 (Cemiplimab); mFOLFOX6 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Patient has provided written informed consent prior to initiation of ANY trial specific activities/procedures.
  • Men or women ≥ 18 years of age.
  • Pathologically documented, locally advanced or metastatic malignancy with KRASG12D mutation identified through molecular testing (NGS- or PCR-based) with a Clinical Laboratory Improvement Amendments-certified (or equivalent) diagnostic.
  • Patient is willing to provide available archived tumor tissue samples (formalin fixed, paraffin embedded [FFPE] sample collected within 5 years) or willing to undergo pretreatment tumor biopsy. Specifics of requirements for tumor tissue samples are detailed in Section 6.7.3 .
  • Part 1: Evaluable or Measurable disease per RECIST 1.1. Parts 2 and 3: Measurable disease per RECIST 1.1.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Life expectancy > 3 months according to Investigator’s assessment.
  • Ability to tolerate oral medications and willingness to provide daily record of adherence. to trial treatment using a Sponsor-provided diary.
  • QTc ≤ 470 msec (using the Fridericia formula).
  • Adequate hematological parameters as defined by the protocol.
  • Creatinine clearance ≥ 50 ml/min (per Cockcroft-Gault equation).
  • Adequate hepatic parameters as defined by the protocol.
  • Adequate coagulation parameters as defined by the protocol.
  • Other criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Active brain metastasis or carcinomatous meningitis. If patients have brain metastases resected or have received radiation therapy, they may be eligible if: (1) trial treatment begins at least 4 weeks from the end of brain-specific therapy, (2) residual neurological symptoms are Grade ≤ 2, (3) patient is on stable doses of corticosteroids, (4) patient is not on anti-epileptic medication, and (5) pre-trial brain magnetic resonance imaging (MRI) indicates no new/worsening brain lesions.
  • Significant cardiovascular disease within 6 months of Day 1, including myocardial infarction, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, cardiac arrhythmia requiring medication, and congenital or family history of long QT syndrome.
  • Significant gastrointestinal disease causing difficulty with oral intake, malabsorption, or requirement for parenteral nutrition; uncontrolled inflammatory bowel disease.
  • Active infection requiring intravenous (IV) antibiotics within 1 week of Day 1.
  • Active or chronic viral hepatitis.
  • Human immunodeficiency virus infection.
  • Clinically uncontrollable third spacing, such as pleural effusion or ascites that cannot be controlled by drainage or other methods prior to enrollment.
  • Unresolved toxicities from prior antitumor-cancer therapies Common Terminology Criteria for Adverse Events [CTCAE] Grades > 1, except for alopecia. Grade ≤ 2 toxicities from prior anti-tumor therapies that are considered irreversible may be allowed, provided they are not described in the exclusion criteria AND the Investigator and medical monitor agree to proceed.
  • Anti-tumor therapy within 14 days of Day 1. Concurrent use of hormonal therapies for hormone-refractory prostate cancer or breast cancer are acceptable.
  • Therapeutic or palliative radiation therapy within 14 days of Day 1. Patients must have recovered from all radiotherapy-related toxicity. Grade 1 toxicities from prior radiation that are considered irreversible may be allowed, provided they are not described in the exclusion criteria AND the Investigator and medical monitor agree to proceed.
  • Concurrent enrollment in another investigational device or drug trial, or less than 28 days or 5 half-lives (whichever is shorter) from ending another investigational device or drug trial.
  • Major surgery within 28 days of Day 1.
  • Men and women of childbearing potential who are unwilling to practice highly effective methods of birth control during treatment. Birth control must continue for at least 92 days for men and at least 182 days for women after receiving the last dose of QTX3034 and for at least 60 days after receiving the last dose of cetuximab (if applicable). Acceptable methods of highly effective birth control are described in Section 7.2.2.
  • Women who are lactating/breast feeding or who plan to breastfeed while on trial through 6 months after receiving the last dose of trial treatment.
  • Women with a positive pregnancy test.
  • Known sensitivity to any of the products to be administered during dosing.
  • Any disease or disorder that, in the opinion of the Investigator, may compromise the ability of the patient to provide written informed consent and/or to comply with all required trial procedures.
  • Any disease or disorder that, in the opinion of the Investigator or medical monitor, may pose a risk to the patient’s safety or interfere with trial evaluation, procedures, or completion.
  • Ongoing need for treatment with a medication with the following characteristics that cannot be switched to alternative treatment prior to study entry
  • Prior treatment with a KRAS-targeting agent, mitogen-activated protein (MAP) kinase-, or son of sevenless homolog 1 (SOS1)-targeting agent.
  • Other criteria may apply

If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.