2945 - Preliminary results of the first-in-human, dose-finding PROCLAIM-CX-072 trial evaluating the PD-L1 Probody therapeutic CX-072 in combination with ipilimumab (ipi) in patients (pts) with advanced solid tumors

Background

Combination treatment with PD-1 + CTLA-4 checkpoint inhibitors shows improvement in breadth, depth, and durability of response, coupled with a disproportionate increase in immune-related adverse events (irAE). CX-072, a Probody™ therapeutic (Pb-Tx) directed against PD-L1, is designed to be preferentially activated by tumor-associated proteases and not in healthy tissue. Preclinically, anti–PD-1 Pb-Tx + anti–CTLA-4 showed comparable efficacy with improved safety compared to the non–Pb-Tx combination control. This dose-escalation cohort examines safety and tolerability of CX-072 (anti-PD-L1 Pb-Tx) + the CTLA-4 inhibitor ipi in pts with advanced solid tumors.

Methods

In this ongoing phase 1/2 study (NCT03013491), PD-1, PD-L1, and CTLA-4 inhibitor-naive pts receive combination CX-072 + ipi (part B1). Planned doses of CX-072 (0.3, 1, 3, or 10 mg/kg) are administered in combination with ipi (3, 6, or 10 mg/kg) every 21 days for 4 cycles, followed by CX-072 monotherapy every 14 days.

Results

As of April 20, 2018, part B1 enrolled 16 pts. Median age (range) and number of prior anticancer treatments was 60 years (28-70) and 3 (1-12), respectively. 6 pts were still on treatment at time of data cut. Median number (range) of CX-072 (0.3, 1, 3, or 10 mg/kg) and ipi (3 mg/kg) doses were 3 (1-20) and 3 (1-4), respectively. All cohorts through 10 mg/kg CX-072 (dose selected for monotherapy cohort expansion) are now enrolled without reaching the MTD. 1 DLT (grade 3 dyspnea, 0.3 mg/kg CX-072 + ipi) occurred. Grade 3 treatment-related (TR) irAEs occurred in 2 pts (12.5%; colitis and dyspnea/pneumonitis). No subject discontinued due to TR irAEs. Best response in 10 evaluable pts included 1 complete response (anal SCC, 0.3 mg/kg CX-072 + ipi), 2 partial response (non-seminoma testicular, 1 mg/kg CX-072 + ipi; small bowel, 3 mg/kg CX-072 + ipi), 1 stable disease, and 6 progressive disease.

Conclusions

Despite small pt numbers and limited follow up, early data suggest manageable safety profiles at all doses and antitumor activity with CX-072 + ipi in tumor types not approved for checkpoint inhibitors. The study is ongoing and escalation of ipi to 10 mg/kg is pending.

Clinical trial identification

NCT03013491.

Legal entity responsible for the study

CytomX Therapeutics, Inc.

Funding

CytomX Therapeutics, Inc.

Editorial Acknowledgement

Editorial support was provided by Andrew Occiano (ApotheCom, San Francisco, CA).

Disclosure

R.E. Sanborn: Research funding/grant: Merck; Investigator initiated Study: BMS, Medimmune; Institutional research support, honoraria: AstraZeneca; Advisory board: AstraZeneca, Seattle Genetics, Takeda, Genentech, Abbvie, Celldex; Travel, accommodations, investigator meeting: Janssen. E.G.E. de Vries: Research grant: Amgen, Genentech, Roche, Chugai, Synthon, CytomX, Nordic Nanovector, Regeneron, G1 Therapeutics, AstraZeneca, Radius Health (institution); Consulting: Pfizer, Sanofi (institution). P. Lorusso: Data safety monitoring board: Agios, FivePrime, Halozyme; Advisory board: Alexion, Ariad, CytomX, GenMab, Genentech, Glenmark, Ignyta, Menarini, Novartis, Omniox, Takeda, imCORE Alliance, Roche-Genentech. N. Uboha: Consulting: EMD Serono, Lilly, FlatIron, GLG. M.J. Fidler: Consulting: Genentech, AstraZeneca, Takeda, AbbVie; Speakers bureau: Merck, Celgene, Genentech, AbbVie. R. Humphrey, M. Will: Employment: CytomX Therapeutics. K.A. Autio: Research funding: CytomX, Pfizer, Lilly, GSK, Merck, ARMO Biosciences. F. Thistlethwaite: Research grant: Novartis; Consulting: Pfizer, BMS, Octimet, Achilles Therapeutics, Evelo Biosciences; Honorarium: Novartis; Speakers' bureau: BMS. All other authors have declared no conflicts of interest.