(888) 552-6760 SCHEDULE A CONSULTATION

A Phase 1b/2, Multicenter, Single Arm Study of RBN-2397 in Combination With Pembrolizumab in Patients With Squamous Cell Carcinoma of the Lung (SCCL)

Description

This is an open label, multicenter, phase 1b/2 single arm study that will evaluate the safety and antitumor activity of RBN-2397 in combination with pembrolizumab in patients with confirmed diagnosis of advanced squamous cell carcinoma of the lung who have received prior therapy. The study consists of a phase 1b safety run in and phase 2.

During the phase 1b Safety run-in, approximately 10 patients will be enrolled in a 3+3 fashion and treated with continuous oral dosing with RBN-2397 twice daily (BID) in combination with the fixed approved dose of intravenous (IV) pembrolizumab every three weeks [Q3W]) to establish RP2D of RBN-2397 in combination with pembrolizumab.

During phase 2, approximately 40 patients will be treated with continuous oral dosing with the RP2D of RBN-2397 BID in combination with the fixed approved dose of IV pembrolizumab.

In both the phase 1b safety run in and phase 2, a treatment cycle is defined as 21 days. On Day 1 of each treatment cycle, RBN-2397 will be administered orally and followed by IV infusion of pembrolizumab at the fixed approved dose according to the approved local product label. During the remaining days of the 21-day treatment cycle, only RBN-2397 BID will be administered. Treatment cycles will continue until disease progression, unacceptable treatment-related toxicity, or withdrawal of consent

Status

Accepting new patients

Primary Study Objective(s)

The primary objective of this study is to:

  • Determine recommended phase 2 dose (RP2D) (phase 1b)
  • Determine overall response rate (phase 2)

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who meet this criteria:

  • Confirmed diagnosis of advanced/metastatic NSCLC of squamous cell histology as determined by local testing practices.
  • Patients should have received prior therapy including a platinum doublet and an ICI, including anti-PD-1/anti-PD-L1, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, either sequentially or as combination of chemo + checkpoint inhibitor.
  • The last regimen prior to enrolling in the study must be an approved checkpoint inhibitor-containing regimen where the best response was stable disease (SD), partial response (PR), or complete response (CR).
  • Patients experienced PD as determined by the investigator during or following their most recent treatment regimen
  • Must agree to undergo tumor biopsy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • CT or MRI imaging done within 28 days prior to study treatment and have at least one measurable target lesion
  • Normal organ and bone marrow function
  • Patient and his/her partner agree to use adequate contraception during and for three months after the last study drug dose

Excluding patients who meet this criteria:

  • Has non-squamous histology NSCLC. Patients whose tumors have a mixed histology are ineligible.
  • Patient must not have received any other investigational systemic therapy for SCCL.
  • Patient should not have received more than two prior lines of therapy with ICI including anti-PD-1/anti-PD-L1, anti-CTLA-4 inhibitors and one prior line of a chemotherapy doublet treatment.
  • Patient is unable to swallow oral medications, has impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption (e.g., active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
  • Prior radiation within 2 weeks of Cycle 1 Day 1 (C1D1), except for palliative radiotherapy to a limited field. Patients must have recovered from all radiation related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non CNS disease.
  • A patient with CNS metastases is excluded if:
  • Patients who discontinue prior treatment with an ICI due to irAEs.
  • Has a known history of prior malignancy. Except: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
  • Has received a live-virus vaccination within 30 days of planned treatment start. Vaccines that do not contain live virus are permitted.
  • Any of the following in the previous six months: myocardial infarction or current history of New York heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular anemias, or electrocardiographic evidence of acute ischemia.
  • Patient has a history of prolonged QT syndrome or Torsades de pointes, and/or has a familial history of prolonged QT syndrome.
  • Patient is taking a concomitant medication that is a strong inhibitor or inducer of cytochrome P450 [CYP]-mediated metabolism or that is metabolized by CYP 2B6, 3A4 or 2C19, 2C9, or other members of the IIC subfamily of the CYP genes and that, if underdosed, would constitute a significant risk to the patient. Individual cases may be discussed with the Medical Monitor.
  • Ingestion of herbal medicines within three weeks before Screening, and grapefruit, grapefruit juice, pomegranate juice, star fruit, or orange marmalade (made with Seville oranges) within one week prior to Screening. (Note that there are well- reported cases of CYP3A drug-drug interactions with these foodstuffs.)
  • Has active autoimmune disease that has required systemic treatment in the past 12 months (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., ≤ 10 mg daily prednisolone or steroid equivalent, thyroxine, insulin, or corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, and residual hypothyroidism due to an autoimmune condition and only requiring hormone replacement, are not excluded.
  • Is on chronic systemic steroids (e.g., > 10 mg daily prednisolone or steroid equivalent for > 6 months). Subjects with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study.
  • Has an active systemic infection requiring therapy (e.g.: bacterial, fungal, viral).
  • Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg result. Active hepatitis C is defined by a known positive hepatitis C Antibody result and known quantitative hepatitis C virus ribonucleic acid (RNA) results greater than the lower limits of detection of the assay.
  • Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
  • Has interstitial lung disease or a history of pneumonitis that required oral or intravenous steroids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary.
  • Is pregnant or breastfeeding or expecting to conceive or father children while on study medication and for the required duration of contraception after the last dose of study medication.
  • Has ongoing acute clinical AEs of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 resulting from prior cancer therapies (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ Grade 3).
  • Has had, within the past 6 months, the occurrence of one or more of the following events: cerebrovascular accident, deep vein thrombosis, pulmonary embolism, hemorrhage (CTCAE Grade 3 or 4), chronic liver disease (meeting criteria for Child Pugh Class B or C), organ transplantation.
  • Has, within two weeks prior to day one, received systemic therapeutic doses of corticosteroids (e.g., > 10 mg daily prednisolone or steroid equivalent). Topical, inhaled, nasal and ophthalmic steroids are allowed for short term treatment of acute conditions (e.g.: asthma, poison ivy contact dermatitis); for other immunosuppressive agents, the exclusionary dose and duration will be determined in consultation with the Medical Monitor.
  • Has any other medical or personal condition that, in the opinion of the Investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's successful completion of the clinical study.