GOG Partners Cervical Trials in Progress: The Checkpoint Era

Session: GOG-P—Improving Care of Women’s Cancer—TiP of the Iceberg”

Speaker: Leslie Randall, MD, VCU Health System, MCV Physicians, Richmond, VA

Three evolving and innovative cervical cancer treatments currently generating serious interest

The clinical development of active immunotherapies has kept scientists, researchers, oncologists, and patients captivated for about a decade. Today, with immune checkpoint inhibition already integrated into standard-of-care across some cancer types, even more clinical trials are now putting checkpoint inhibitors to the test.

As part of the larger SGO 2021 session covering trials in progress for women’s cancer care, there was a deep dive into three current cervical cancer trials, led by Leslie Randall, MD, VCU Health System, MCV Physicians, Richmond, VA. Dr. Dr. Randall also runs the cervical cancer trial portfolio for GOG Partners, an international leader in gynecologic malignancies research.

As a segue into her trial presentation, Dr. Randall said, “We’re getting really interesting and exciting results that just give us more confidence that we’re on the right track in these upcoming three trials.”

Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047)

This study evaluates the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer.

The primary hypothesis is that pembrolizumab plus concurrent chemoradiotherapy is superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival and overall survival.

Once study objectives are met or the study ends, participants will be enrolled in an extension study to continue protocol-defined assessments and treatment.

The goal is to accrue around 1,000 patients, stage IB2-IIB (with node-positive disease) or stages III-IVA (node-positive or negative disease). Participants will receive pembrolizumab 200 mg intravenously on day 1 of each 3-week cycle for 5 cycles followed by pembrolizumab 400 mg IV on day 1 of each 6-week cycle for an additional 15 cycles.

The primary outcome measures are primary progression-free survival per response evaluation criteria in solid tumors version 1.1, and overall survival.

Platinum Chemotherapy Plus Paclitaxel With Bevacizumab and Atezolizumab in Metastatic Carcinoma of the Cervix (BEATcc)

The BEATcc trial is designed to enroll patients with primary stage IVB persistent or recurrent cervical cancer with measurable disease and good performance status. The randomized, open label, phase III trial, with no patient selection based on PD-L1 expression, is set to investigate the efficacy of combining the anti-programmed death-ligand 1 (anti-PD-L1) agent atezolizumab with bevacizumab and cisplatin or carboplatin /paclitaxel chemotherapy on overall survival.

Study participants will be randomly assigned to one of the two arms:

  1. Arm A: Cisplatin 50mg/m2 or carboplatin AUC 5 + paclitaxel 175mg/m2+ bevacizumab 15mg/kg i.v D1 Q3W. Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologic therapy, namely bevacizumab, upon investigator discussion.
  2. Arm B: cisplatin 50mg/m2 or carboplatin AUC 5 + paclitaxel 175mg/m2 + bevacizumab 15mg/kg + atezolizumab 1200mg i.v, D1 Q3W. Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologics therapy, namely bevacizumab plus atezolizumab, upon investigator discussion.

The primary outcome measure is overall survival.

“For the first time, we have a very active treatment in the second line for cervical cancer that will start to make overall survival a typical endpoint to interpret,” Dr. Randall said. “It is much like what happened with ovarian cancer—when we started to get more active post-progression therapies. So it will be very interesting to see the results of this study.”

Two-arm, Randomized, Non-comparative, Phase 2 Trial of AGEN2034 (Anti-PD-1) as a Monotherapy or Combination Therapy With AGEN1884 (Anti-CTLA4) or With Placebo in Women With Recurrent Cervical Cancer (Second Line)—RaPiDS

This is a randomized, blinded, non-comparative, two-arm, phase II clinical trial, and it’s designed to assess the efficacy and safety of balstilimab administered with placebo (Treatment Arm 1 – smonotherapy) or with zalifrelimab (Treatment Arm 2 – combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy. The study is not intended to compare the efficacy of the two experimental arms. Instead, the efficacy of each arm will be evaluated against its relevant historical controls as appropriate.

The primary outcome measure is objective response rate.

“The CTLA4 addition is very exciting,” Dr Randall said. “It may increase responses in PDL1 negative and adenocarcinoma in addition to the PDL1 one patients.”