Patient case: 68-year-old male with melanoma; genetic feature: PTEN loss of function

Clinical trial: Phase 1 Study of IMP321 Adjuvant to Anti-PD-1 Therapy in Unresectable or Metastatic Melanoma

Summary: The purpose of this study is to determine the safety, tolerability and recommended phase 2 dose of a new drug, known as IMP321, in combination with pembrolizumab when given to patients with unresectable or metastatic melanoma.


Eligibility: Inclusion Criteria
  1. Able to give written informed consent and to comply with the protocol
  2. Histologically confirmed diagnosis of locally advanced (unresectable Stage III) or metastatic (Stage IV) melanoma
  3. Currently receiving anti-PD-1 therapy with pembrolizumab and after 3 cycles achieved asymptomatic irPD (slowly progressive, not requiring urgent intervention, and stable performance status) or sub-optimal response (irSD, irPR) as demonstrated in imaging assessments performed within 6 weeks prior to day 1 of cycle 5 of pembrolizumab.
  4. Female or male 18 years of age or above
  5. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 4 months after the last administration of study treatment.
  6. ECOG performance status 0-1
  7. Expected survival longer than three months
  8. Resolution of toxicity associated with prior or current therapy to grade < 2 (except for alopecia and transaminases in case of liver metastases)
  9. Evidence of measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1
  10. Laboratory criteria:
  -  Absolute neutrophil count > 1.5 x 109/L
  -  Platelet count ≥ 100 x 109/L
  -  Haemoglobin > 9 g/dL or 5.58 mmol/L
  -  Serum creatinine ≤ 1.5 × ULN
  -  Total bilirubin < 20 mmol/L, except for familial cholemia (Gilbert's disease)
  -  Serum AST (=GOT) and ALT (=GPT) < 3 times the upper limit of normal or < 5 times upper limit of normal if liver metastases are present
  Exclusion Criteria
  1. More than four prior lines of therapies for advanced or metastatic disease.
  2. Prior PD-1/PDL-1 targeted therapy
  3. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue
  4. Currently receiving treatment with another investigational drug, or less than 4 weeks since ending treatment on another investigational drug
  5. Currently receiving systemic chemotherapy, targeted small molecule therapy, radiotherapy, or biological cancer therapy (other than pembrolizumab) or less than 4 weeks since completion of these therapies and first dose of study treatment
  6. History of irAEs from ipilimumab of CTCAE Grade 4 requiring steroid treatment
  7. Known cerebral or leptomeningeal metastases. (Some subjects with previously treated brain metastases may participate under specific circumstances)
  8. Women who are pregnant or lactating
  9. Serious intercurrent infection within 4 weeks prior to first dose of study treatment
  10. Evidence of severe or uncontrolled cardiac disease (NYHA III-IV) within 6 months prior to first dose of study treatment
  11. Active acute or chronic infection
  12. History or evidence of interstitial lung disease or active non-infectious pneumonitis
  13. Active auto-immune disease requiring immunosuppressive therapy
  14. HIV positivity
  15. Active hepatitis B or hepatitis C, currently treated with antiviral therapy
  16. Life threatening illness unrelated to cancer
  17. Previous malignancies within the last three years other than melanoma
  18. Any current disorder that would impede the patient's ability to provide informed consent or to comply with the protocol
  19. Continuous systemic treatment with either corticosteroids or other immunosuppressive medications within 4 weeks prior to first dose of study treatment
  20. History or evidence of severe allergic episodes and/or angioedema
  21. Any current disorder likely to modify absorption, distribution or elimination of IMP321
  22. Alcohol or substance abuse disorder
  23. Known hypersensitivity to any of the components of IMP321
  24. Unwilling or unable to follow protocol requirements
  25. In the clinical judgment of the investigator, the patient is unsuitable for participation in this study

Relevance to patient case: not relevant