The document presents an overview of adjuvant therapy and clinical trials for melanoma, discussing their definitions, trial designs, and specific interventions for high-risk patients. It highlights various treatment approaches including interferon, ipilimumab, and peptide vaccines, along with the challenges faced in patient enrollment and compliance. Current and future options for adjuvant therapies are also mentioned, emphasizing the significance of clinical trials in advancing melanoma treatment.

1. ADJUVANT THERAPY
AND
CLINICAL TRIALS
Sapna Patel, M.D.
Melanoma Medical Oncology
7th Annual
Eyes on a Cure:
Ocular Melanoma Patient and
Caregiver Symposium
April 21, 2018

2. ADJUVANT THERAPY

3. Two definitions
• Treatment given to prevent
recurrence or spread of cancer
• Secondary prevention
• Vaccine-modifying agent
• MMR: Aluminum-based
• Cancer vaccines: water-in-oil
emulsions

4. Adjuvant Trial Design:
How do we do this?

5. High-Risk
Patients
Intervention
RFS/OS
3yr DMFS
Single-arm
33-135 Patients

6. High-Risk
Patients
Intervention
RFS/OS
3yr DMFS
Observation
RFS/OS
3yr DMFS
1:1 Randomization
135-544 Patients
R

7. High-Risk
Patients
Intervention
RFS/OS
3yr DMFS
Observation
RFS/OS
3yr DMFS
2:1 Randomization
145-599 Patients
R

8. High-Risk
Patients
c-met
inhibitor
RFS/OS
3yr DMFS
MEK
inhibitor
RFS/OS
3yr DMFS
HDAC
inhibitor
RFS/OS
3yr DMFS
Immune
therapy
RFS/OS
3yr DMFS
Multi-arm Randomization
700-800 Patients
R

9. Appropriate Adjuvant
Therapies
Trial
Design
Targets
High-risk
Population

11. Interferon for Uveal Melanoma
Stefan Dithmar, MD; Dario Rusciano, PhD; Michael J. Lynn, MS; David H. Lawson,
MD; Cheryl A. Armstrong, MD; Hans E. Grossniklaus, MD
2-year course of IFNa
• 3 MIU subq TIW
• Initiated within 3 years of primary tx
n = 121 patients
• >= 65 years od
• LTD >= 15 mm
• Ciliary body involvement
• Extrascleral extension
118 pts tx with proton
3 pts tx with enucleation
55 patients completed tx
Median f/u 9.5 years
No difference in melanoma-related
mortality c/w matched controls

12. Adjuvant DTIC plus IFNa in High Risk UM
• Iris, Ciliary Body, or Choroid melanoma
• Monosomy 3
• Completed primary therapy, no distant disease
• Enrolled within 56 days (8 weeks) of primary therapy
• DTIC 850 mg/m2 IV Day 1 and Day 28
• IFNa 3 million IU SQ TIW x 24 weeks beginning Week 9
Awaiting results

14. High-risk UM
Class 2 or
Mono 3 +
Apical>=8mm
Ipilimumab 3mg/kg
(n=3 to 6)
induction
Ipilimumab 10 mg/kg
(n=31 to 35)
induction
Ipilimumab
Maintenance
Weeks 24, 36, 48
Phase I/II Study: Ipilimumab (Adjuvant Therapy)
for high-risk UM
Original N = 89

15. Patient Date of first Ipi Dose of Ipi Doses
(max = 7)
Grade 3/4 AEs Reason
1 03/2013 3 mg/kg 7 Colitis Completed 1 year
2 03/2013 3 mg/kg 7 ALT/AST Completed 1 year
3 04/2013 3 mg/kg 6 Rash, Pruritus Completed 1 year
4 05/2013 10 mg/kg 7 Pruritus Completed 1 year
5 05/2013 10 mg/kg 2 Vasculitis SAE
6 05/2013 10 mg/kg 2 Colitis, ALT, AST SAE
7 06/2013 10 mg/kg 7 ____ Completed 1 year
8 07/2013 10 mg/kg 6 Adrenal Insuff Completed 1 year
9 07/2013 10 mg/kg 7 ALT/AST Completed 1 year
10 09/2013 10 mg/kg 7 ____ Completed 1 year

16. Hepatic radiation
• Mon-Fri x 20 minutes for up to 10 fractions over 2 weeks
• Planned enrollment of 50 patients
Terminated after 1 year for slow
enrollment

17. Peptide vaccine
• MART-1, gp100, Tyr, NA17-A
• Planned enrollment of 600 patients randomized to vaccine or
observation
Terminated for slow enrollment

18. Current Adjuvant Uveal Melanoma Trials
• Crizotinib (n=30 in 2014, changed to 10 in 2016)
– Class 2 tumors and LTD >=12 mm
– 90 day window from primary tx
– 48 weeks of treatment
• Sunitinib or valproic acid (n=90)
– Monosomy 3 + 8q amplification –or- Class 2 tumors
– 180 day window from primary tx
– 6 months of treatment

19. Future options
• Adjuvant peptide vaccine
• Adjuvant nivolumab + ipilimumab
• Immunocore IMC gp100 (HLA*A:0201)

20. Laboratory based trials
• HDAC inhibitor assays
• Liquid biopsy
• Microbiome

21. Trials versus Off-protocol
Clinical Trials
Pros
• Covered by
insurance
• Study drugs are
free
• Science-driven
• Research RN as a
point person
• Side effects
captured
Cons
• Frequent visits
• Compliance rules
• Strict eligibility
criteria
• Discontinuation
of study / drug
Off-Protocol
Pros
• Liberal inclusion
• Flexible schedule
Cons
• Not always
supported by
insurance
• Costly drugs
• Data outputs
• Side effects not
captured as
methodically
• No point person

22. ACKNOWLEDGEMENTS
• Patients and Families who participate in clinical trials
• Faculty, Staff, Researchers at MD Anderson Cancer Center
• Collaborators outside MD Anderson
• Melanoma and Skin Center: (713) 563-9716